Kawasaki Disease: MedlinePlus Health Topic

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... Medicine) Also in Spanish What Is Echocardiography? (National Heart, Lung, and Blood Institute) Treatments and Therapies Kawasaki Disease: Complications, Treatment and Prevention (American Heart ...

Association between Kawasaki Disease and Autism: A Population-Based Study in Taiwan

PubMed Central

Kuo, Ho-Chang; Wu, Chung-Min; Chang, Wei-Pin; Kuo, Chun-Nan; Yeter, Deniz; Lin, Chun-Yi; Pai, Jei-Tsung; Chi, Ying-Chen; Lin, Chia-Hsien; Wang, Liang-Jen; Chang, Wei-Chiao

2014-01-01

Objective: The association between Kawasaki disease and autism has rarely been studied in Asian populations. By using a nationwide Taiwanese population-based claims database, we tested the hypothesis that Kawasaki disease may increase the risk of autism in Taiwan. Materials and Methods: Our study cohort consisted of patients who had received the diagnosis of Kawasaki disease (ICD-9-CM: 446.1) between 1997 and 2005 (N = 563). For a comparison cohort, five age- and gender-matched control patients for every patient in the study cohort were selected using random sampling (N = 2,815). All subjects were tracked for 5 years from the date of cohort entry to identify whether they had developed autism (ICD-9-CM code 299.0) or not. Cox proportional hazard regressions were then performed to evaluate 5-year autism-free survival rates. Results: The main finding of this study was that patients with Kawasaki disease seem to not be at increased risk of developing autism. Of the total patients, four patients developed autism during the 5-year follow-up period, among whom two were Kawasaki disease patients and two were in the comparison cohort. Further, the adjusted hazard ratios (AHR) (AHR: 4.81; 95% confidence interval: 0.68–34.35; P = 0.117) did not show any statistical significance between the Kawasaki disease group and the control group during the 5-year follow-up. Conclusion: Our study indicated that patients with Kawasaki disease are not at increased risk of autism. PMID:24705358

Kawasaki disease and giant coronary artery aneurysms: the role of echocardiography from diagnosis through follow-up.

PubMed

Adler, Adam C; Kodavatiganti, Ramesh

2016-08-01

Kawasaki disease is an acquired vasculitis that can affect the coronary arteries placing the patient at risk for coronary artery thrombosis, myocardial ischemia and infarction. The risk of complications related to coronary artery involvement persists for years despite recovery from the acute illness phase. The risk of late coronary disease progression necessitates long term follow-up generally accomplished by non-invasive echocardiography in pediatric patients. We review the utility of echocardiography in patients with Kawasaki disease as it relates to initial management, risk stratification and follow-up of these children. © 2016, Wiley Periodicals, Inc.

Kawasaki disease: State of the art.

PubMed

Newburger, Jane W

2017-09-01

Kawasaki disease is an acute febrile arteritis of childhood that can result in coronary artery aneurysms if untreated in the first 10 and ideally 7 days of illness. Kawasaki disease begins as a necrotizing arteritis with neutrophilic infiltrate, followed by subacute/chronic changes and luminal myofibroblastic proliferation that can cause coronary artery stenosis. Manifestations include the presence of ≥5 days of fever, together with clinical criteria of extremity changes, rash, conjunctivitis, oral changes, and unilateral cervical lymphadenopathy. Echocardiography should be performed at the time of diagnosis, then 1-2 weeks and 4-6 weeks later, with more frequent studies in individuals with coronary artery dilation or persistent fever. Coronary artery dimensions are characterized both as z-scores and absolute measurements, and coronary architecture evolves over time in children who have aneurysms in the first weeks of illness. Systematic follow-up and therapies are tailored to the degree of coronary disease and to coronary ischemia. © 2017 Wiley Periodicals, Inc.

Kawasaki Disease Increases the Incidence of Myopia.

PubMed

Kung, Yung-Jen; Wei, Chang-Ching; Chen, Liuh An; Chen, Jiin Yi; Chang, Ching-Yao; Lin, Chao-Jen; Lim, Yun-Ping; Tien, Peng-Tai; Chen, Hsuan-Ju; Huang, Yong-San; Lin, Hui-Ju; Wan, Lei

2017-01-01

The prevalence of myopia has rapidly increased in recent decades and has led to a considerable global public health concern. In this study, we elucidate the relationship between Kawasaki disease (KD) and the incidence of myopia. We used Taiwan's National Health Insurance Research Database to conduct a population-based cohort study. We identified patients diagnosed with KD and individuals without KD who were selected by frequency matched based on sex, age, and the index year. The Cox proportional hazards regression model was used to estimate the hazard ratio and 95% confidence intervals for the comparison of the 2 cohorts. The log-rank test was used to test the incidence of myopia in the 2 cohorts. A total of 532 patients were included in the KD cohort and 2128 in the non-KD cohort. The risk of myopia (hazard ratio, 1.31; 95% confidence interval, 1.08-1.58; P < 0.01) was higher among patients with KD than among those in the non-KD cohort. The Cox proportional hazards regression model showed that irrespective of age, gender, and urbanization, Kawasaki disease was an independent risk factor for myopia. Patients with Kawasaki disease exhibited a substantially higher risk for developing myopia.

Myocardial infarction in a 35-day-old infant with incomplete Kawasaki disease and chicken pox.

PubMed

Kossiva, Lydia; Papadopoulos, Marios; Lagona, Evangelia; Papadopoulos, George; Athanassaki, Corina

2010-10-01

Kawasaki disease is an acute febrile vasculitis of infancy and early childhood. It is uncommon in early infancy, because a significant proportion of these children do not meet the classical diagnostic criteria at this age. Infants younger than 6 months with persistent fever and some of the criteria of Kawasaki disease should always raise suspicion for Kawasaki disease early to avoid delayed diagnosis with severe cardiac complications. We present a 35-day-old infant with incomplete Kawasaki disease complicated with myocardial infarction during chicken pox.

Absence of association of FCGR2A gene polymorphism rs1801274 with Kawasaki disease in Greek patients.

PubMed

Chatzikyriakidou, Anthoula; Aidinidou, Louiza; Giannopoulos, Andreas; Papadopoulou-Legbelou, Kyriaki; Kalinderi, Kallirhoe; Fidani, Liana

2015-04-01

Kawasaki disease is an acute, febrile syndrome in infancy, characterised by vasculitis of medium-sized arteries, and affects predominantly young children. Family-based studies on Kawasaki disease supports the contribution of genetic factors in disorder manifestation. In a recent genome-wide association study, the polymorphism rs1801274 of FCGR2A [Fc fragment of immunoglobulin G, low-affinity IIa, receptor] gene has been implicated in disease pathogenesis. The aim of the present study was to explore the association of this variant, for the first time, in a group of Kawasaki-diseased patients of Greek origin. A total of 47 Kawasaki-diseased children and 50 control subjects were enrolled in the study. Polymerase chain reaction-restriction fragment length polymorphism assay was performed in rs1801274 genotyping. No association was observed between this polymorphism genotypes' or alleles' distribution between Kawasaki-diseased patients and controls. Furthermore, no association was revealed between this polymorphism and cardiovascular complications in Kawasaki-diseased patients. In the literature, the reported data over this polymorphism association with Kawasaki disease in Caucasian patients are contradictory. In addition, the disease shows low prevalence in the Caucasian populations. Therefore, the independent genetic association studies on rs1801274 with Kawasaki disease in various Caucasian groups increase the amount of genetic data, which could be used in a future meta-analysis, increasing the statistical power of the resultant conclusions.

Response of refractory Kawasaki disease to pulse steroid and cyclosporin A therapy.

PubMed

Raman, V; Kim, J; Sharkey, A; Chatila, T

2001-06-01

We describe a child with aggressive and protracted Kawasaki disease with coronary aneurysms, myocarditis, pericarditis and valvular insufficiency, despite repeated administration of intravenous immunoglobulin. After a transient response to pulse corticosteroids, his disease ultimately subsided with combination therapy with pulse and high dosage corticosteroids and cyclosporin A. Aggressive immunosuppressive therapy with high dosage corticosteroids and cyclosporin A may be beneficial in patients with refractory Kawasaki disease.

Kawasaki Disease: Complications, Treatment and Prevention

MedlinePlus

... Even if there is no evidence of a heart abnormality when your child recovers from the acute phase of Kawasaki disease, it is important to bring your child in for a follow-up visit with your doctor to be sure that there aren't heart problems that did not show up right away. ...

Comparison of early and late intravenous gamma globulin treatment of Kawasaki disease on fever and cardiovascular complications

PubMed Central

Mohammadzadeh, Iraj; Noei, Somayyeh; Babazadeh, Kazem; Zamani, Hassan; Barari-Savadkoohi, Rahim; Alizadeh-Navaei, Reza

2016-01-01

Background: Cardiac involvement was the major leading cause of death in patients with Kawasaki and IVIG administration reduces cardiac complications. The objective of this study was to determine the frequency of cardiovascular complications and duration of fever with regard to the time of intravenous immunoglobulin (IVIG) administration of patients with Kawasaki disease. Methods: This follow-up study was done on all patients with Kawasaki disease who were hospitalized at Amirkola Children’s Hospital between 2006 and 2011. Diagnosis of Kawasaki was clinical and included fever more than 5 days with 4 of 5 signs containing mucosal changes, scaling and skin rash, bilateral nonexudative conjunctivitis, cervical lymph adenopathy and edema in lower extremities. After diagnosis of Kawasaki, all patients received standard treatment (intravenous immunoglobulins and aspirin) and undergoing cardiac echocardiography in 2 weeks, 2 months and 6 months. Information including age, sex, sign of diseases, laboratory findings, and cardiac complications in echocardiography were recorded. Results: This study was performed on 100 patients (61 boys and 39 girls) with Kawasaki disease. The mean age of children was 2.8±2.6 years. Cardiac complication rate was 47% at the onset of the disease and had reached to 7% at the end of the sixth month (P=0.000). Distribution of cardiovascular complications in the second week, the second month and the sixth month after treatment was not significantly different according to the start of time of treatment (p>0.05). Duration of fever in patients who received treatment before 10th day (1.5±1.3) did not have significant difference (P=0.78) with patients who received after 10th day (1.6±0.9). Conclusion: Result shows that most of patients (99%) responded to the treatment with IVIG and ASA and cardiovascular complication ratio decreased. There was not significant relationship between duration of fever and time of IVIG treatment initiation. PMID:27757208

Establishment of Kawasaki disease database based on metadata standard.

PubMed

Park, Yu Rang; Kim, Jae-Jung; Yoon, Young Jo; Yoon, Young-Kwang; Koo, Ha Yeong; Hong, Young Mi; Jang, Gi Young; Shin, Soo-Yong; Lee, Jong-Keuk

2016-07-01

Kawasaki disease (KD) is a rare disease that occurs predominantly in infants and young children. To identify KD susceptibility genes and to develop a diagnostic test, a specific therapy, or prevention method, collecting KD patients' clinical and genomic data is one of the major issues. For this purpose, Kawasaki Disease Database (KDD) was developed based on the efforts of Korean Kawasaki Disease Genetics Consortium (KKDGC). KDD is a collection of 1292 clinical data and genomic samples of 1283 patients from 13 KKDGC-participating hospitals. Each sample contains the relevant clinical data, genomic DNA and plasma samples isolated from patients' blood, omics data and KD-associated genotype data. Clinical data was collected and saved using the common data elements based on the ISO/IEC 11179 metadata standard. Two genome-wide association study data of total 482 samples and whole exome sequencing data of 12 samples were also collected. In addition, KDD includes the rare cases of KD (16 cases with family history, 46 cases with recurrence, 119 cases with intravenous immunoglobulin non-responsiveness, and 52 cases with coronary artery aneurysm). As the first public database for KD, KDD can significantly facilitate KD studies. All data in KDD can be searchable and downloadable. KDD was implemented in PHP, MySQL and Apache, with all major browsers supported.Database URL: http://www.kawasakidisease.kr. © The Author(s) 2016. Published by Oxford University Press.

Clinical spectrum of Kawasaki disease in infants younger than 6 months of age.

PubMed

Burns, J C; Wiggins, J W; Toews, W H; Newburger, J W; Leung, D Y; Wilson, H; Glodé, M P

1986-11-01

We report an unselected series of eight patients younger than 6 months of age with Kawasaki disease evaluated between January 1982 and May 1984. The incidence of coronary artery aneurysms (six patients) and the mortality (two patients) were unusually high in this small series. Because of the confusing clinical presentation in three patients, diagnosis was delayed until pathologic or echocardiographic evidence of coronary vasculitis or aneurysm was discovered. The currently accepted clinical criteria for Kawasaki disease may not always identify patients with the pathologic findings of the syndrome who are younger than 6 months of age. The diagnosis of Kawasaki disease and echocardiographic evaluation of the coronary arteries should be considered in young infants with prolonged fever of unknown origin.

Vaccines and Kawasaki disease.

PubMed

Esposito, Susanna; Bianchini, Sonia; Dellepiane, Rosa Maria; Principi, Nicola

2016-01-01

The distinctive immune system characteristics of children with Kawasaki disease (KD) could suggest that they respond in a particular way to all antigenic stimulations, including those due to vaccines. Moreover, treatment of KD is mainly based on immunomodulatory therapy. These factors suggest that vaccines and KD may interact in several ways. These interactions could be of clinical relevance because KD is a disease of younger children who receive most of the vaccines recommended for infectious disease prevention. This paper shows that available evidence does not support an association between KD development and vaccine administration. Moreover, it highlights that administration of routine vaccines is mandatory even in children with KD and all efforts must be made to ensure the highest degree of protection against vaccine-preventable diseases for these patients. However, studies are needed to clarify currently unsolved issues, especially issues related to immunologic interference induced by intravenous immunoglobulin and biological drugs.

Far East Scarlet-like Fever Masquerading as Adult-onset Kawasaki Disease.

PubMed

Ocho, Kazuki; Iwamuro, Masaya; Hasegawa, Kou; Hagiya, Hideharu; Rai, Kammei; Yumoto, Tetsuya; Otsuka, Fumio

2018-02-01

A previously healthy 31-year-old man was referred to us with refractory septic shock accompanied by bilateral conjunctival congestion and erythema of his right lower limb. Nine days after admission, he had bilateral desquamation of the fingertips, and his presentation satisfied the criteria for Kawasaki disease. A serological examination was positive for Yersinia pseudotuberculosis, and he was diagnosed with Far East scarlet-like fever (FESLF). Interestingly, his 11-month-old baby boy had similar symptoms around the same time, indicating the intrafamilial transmission of the pathogen. We should consider FESLF when we encounter a familial occurrence of systemic manifestations of Kawasaki disease.

Coronary artery lesions and the increasing incidence of Kawasaki disease resistant to initial immunoglobulin.

PubMed

Kibata, Tetsuhiro; Suzuki, Yasuo; Hasegawa, Shunji; Matsushige, Takeshi; Kusuda, Takeshi; Hoshide, Madoka; Takahashi, Kazumasa; Okada, Seigo; Wakiguchi, Hiroyuki; Moriwake, Tadashi; Uchida, Masashi; Ohbuchi, Noriko; Iwai, Takashi; Hasegawa, Masanari; Ichihara, Kiyoshi; Yashiro, Mayumi; Makino, Nobuko; Nakamura, Yosikazu; Ohga, Shouichi

2016-07-01

Kawasaki disease (KD) is a systemic vasculitis of childhood involving coronary arteries. Treatment for intractable cases at a higher risk of cardiac sequelae remains controversial. Clinical outcomes of KD patients diagnosed in Yamaguchi prefecture, Japan between 2003 and 2014 were analyzed using the medical records from all 14 hospitals covering the prefecture. The study included 1487 patients (male:female, 873:614; median age at diagnosis, 24months). The proportion of initial intravenous immunoglobulin (IVIG)-resistant patients increased from 7% to 23% during this decade, although no patients died. Twenty-four patients developed coronary artery lesions (CALs) over one month after the KD onset. The incidence of CAL in patients who received corticosteroid during the disease course (10/37; 27.0%) was higher than that in those who did not (14/1450; 0.97%, p=2.0×10(-35)). Nine patients who responded to initial IVIG plus corticosteroids had no CAL. Conversely, IVIG-resistant patients with alternate corticosteroid therapy more frequently developed CAL than those without it (10/28; 35.7% vs. 5/194; 2.6%, p=8.9×10(-10)). Multivariate analyses indicated corticosteroid therapy (p<0.0001), hyperbilirubinemia (p=0.0010), and a longer number of days before treatment (p=0.0005) as risk factors associated with CAL over a month after onset. The odds ratio of corticosteroid use increased from 18.3 to 43.5 if the cases were limited to initial IVIG non-responders and corticosteroid free-IVIG responders. IVIG-failure has recently increased. The incidence of CAL increased in intractable cases with prolonged corticosteroid use. Corticosteroid may not be alternate choice for IVIG-failure to reduce the risk of cardiac sequelae. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Far East Scarlet-like Fever Masquerading as Adult-onset Kawasaki Disease

PubMed Central

Ocho, Kazuki; Iwamuro, Masaya; Hasegawa, Kou; Hagiya, Hideharu; Rai, Kammei; Yumoto, Tetsuya; Otsuka, Fumio

2017-01-01

A previously healthy 31-year-old man was referred to us with refractory septic shock accompanied by bilateral conjunctival congestion and erythema of his right lower limb. Nine days after admission, he had bilateral desquamation of the fingertips, and his presentation satisfied the criteria for Kawasaki disease. A serological examination was positive for Yersinia pseudotuberculosis, and he was diagnosed with Far East scarlet-like fever (FESLF). Interestingly, his 11-month-old baby boy had similar symptoms around the same time, indicating the intrafamilial transmission of the pathogen. We should consider FESLF when we encounter a familial occurrence of systemic manifestations of Kawasaki disease. PMID:29093407

Kawasaki syndrome: a case report.

PubMed

Blakeley, S L; Cohen, P R

1993-08-01

A four-year-old black boy with Kawasaki syndrome is reported. The child was treated with intravenous gamma globulin and aspirin. He had no disease-associated adverse sequelae. The clinical findings, diagnostic criteria, and treatment of Kawasaki syndrome are reviewed.

The association between the miRNA-146a rs2910164 C>G polymorphism and Kawasaki disease in a southern Chinese population.

PubMed

Zhang, Li; Wang, Jinxin; Che, Di; Wang, Yanfei; Rong, Xing; Pi, Lei; Xu, Yufen; Li, Wei; Huang, Ping; Chu, Maoping; Gu, Xiaoqiong

2018-06-14

miRNA-146a plays a critical role in innate immune and inflammatory responses. Kawasaki disease involves immune-mediated inflammatory responses, which lead to vascular endothelial injury. However, there has been no study on the association between the miRNA-146a rs2910164 C>G polymorphism and Kawasaki disease risk. We enrolled 532 Kawasaki disease patients and 623 healthy controls from a southern Chinese population, and the miRNA-146a rs2910164 C>G polymorphism was genotyped by the TaqMan method. There was no evidence that this polymorphism was associated with Kawasaki disease. Stratified analysis also showed no significant association. This study indicates that the miRNA-146a rs2910164 C>G polymorphism may not be associated with Kawasaki disease in a southern Chinese population. Larger, multicenter studies are needed to confirm our conclusions. ©2018 The Author(s).

Comparation of clinical and paraclinical findings among patient with Kawasaki disease in Bandar abbas Koodakan Hospital in 2011-14

NASA Astrophysics Data System (ADS)

Borjali, Davood

Title: Comparation of clinical and paraclinical findings among patient with Kawasaki disease in Bandar abbas Koodakan Hospital in 2011-14 Kawasaki disease(KD) is a kind of vasculitis diagnosed by clinical manifestation and it caused acquired heart disease in children because of coronary arteries involvement. Method: patient divided to three group of American Japanese and incomplete and also study in two group according to fever days and then clinical features and laboratory data were checked. Result: A total of 150 patients were enrolled during the study period. number of patients with incomplete Kawasaki disease was 128 american group was 28 and Japanese was 4 patients, the most prevalent symptom was scaling of extremities(61 bladder most seen in group with fever more than five days. Keyword: Kawasaki , epidemiology , criteria

The epidemiology of Kawasaki disease: a global update.

PubMed

Singh, Surjit; Vignesh, Pandiarajan; Burgner, David

2015-11-01

Kawasaki disease (KD) is a childhood vasculitis and the most frequent cause of paediatric acquired heart disease in North America, Europe and Japan. It is increasingly recognised in rapidly industrialising countries such as China and India where it may replace rheumatic heart disease as the most common cause of acquired heart disease in children. We review the current global epidemiology of KD and discuss some public health implications. 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.

Japanese scoring systems to predict resistance to intravenous immunoglobulin in Kawasaki disease were unreliable for Caucasian Israeli children.

PubMed

Arane, Karen; Mendelsohn, Kerry; Mimouni, Michael; Mimouni, Francis; Koren, Yael; Simon, Dafna Brik; Bahat, Hilla; Helou, Mona Hanna; Mendelson, Amir; Hezkelo, Nofar; Glatstein, Miguel; Berkun, Yackov; Eisenstein, Eli; Aviel, Yonatan Butbul; Brik, Riva; Hashkes, Philip J; Uziel, Yosef; Harel, Liora; Amarilyo, Gil

2018-05-24

This study assessed the validity of using established Japanese risk scoring methods to predict intravenous immunoglobulin (IVIG) resistance to Kawasaki disease in Israeli children. We reviewed the medical records of 282 patients (70% male) with Kawasaki disease from six Israeli medical centres between 2004-2013. Their mean age was 2.5 years. The risk scores were calculated using the Kobayashi, Sano and Egami scoring methods and analysed to determine if a higher risk score predicted IVIG resistance in this population. Factors that predicted a lack of response to the initial IVIG dose were identified. We found that 18% did not respond to the first IVIG dose. The three scoring methods were unable to reliably predict IVIG resistance, with sensitivities of 23-32% and specificities of 67-87%. Calculating a predictive score that was specific for this population was also unsuccessful. The factors that predicted a lacked of response to the first IVIG dose included low albumin, elevated total bilirubin and ethnicity. The established risk scoring methods created for Japanese populations with Kawasaki disease were not suitable for predicting IVIG resistance in Caucasian Israeli children and we were unable to create a specific scoring method that was able to do this. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

[Kawasaki disease in children and adolescents].

PubMed

Neudorf, U

2011-12-01

Kawasaki disease (KD) is a systemic vasculitis of unknown etiology. The diagnostic criteria are fulfilled with fever of unknown origin and 4 of the following 5 criteria: bilateral conjunctival injection, cervical lymphadenopathy, polymorphous rash, oral mucous membrane changes (injected lips, strawberry tongue) and peripheral extremity changes (erythema, edema, desquamation). If less than 4 criteria are found incomplete KD can be diagnosed. The therapy is 2 g/kg body weight single dose intravenous immunoglobulin and acetylsalicylic acid (ASS). In the long-term follow-up the main focus is on the coronary arteries because coronary changes play a key role in the intensity of long-term management. There is some evidence that KD is a risk factor for cardiovascular diseases in adults.

The incidence of Kawasaki disease after vaccination within the UK pre-school National Immunisation Programme: an observational THIN database study.

PubMed

Hall, Gillian C; Tulloh, Robert Mr; Tulloh, Louise E

2016-11-01

To provide expected incidence rates of Kawasaki disease after vaccination in routine clinical practice and as recommended within a pre-school National Immunisation Programme (NIP). A post-immunisation risk period when Kawasaki disease onset might be associated with vaccination was defined as 28 days. Immunisation records for children under 6 years were identified from The Health Improvement Network (THIN) database of electronic UK primary health care records (2008-2012) and linked to previously validated cases of Kawasaki disease with an assigned date of onset. Kawasaki disease incidence in the risk period after a complete NIP recommended set of vaccinations was estimated for five vaccination stages individually and in total. A total of 642 170 complete pre-school immunisation stages from 275 986 children were included. Six cases of Kawasaki disease had onset in the risk period after any NIP stage providing an incidence of 12.8 per 100 000 person years (95%CI 5.7, 28.4). The incidence after any single immunisation stage ranged from 0 to 27.4 (95%CI 8.8, 84.8) per 100 000 person years. There were few cases of Kawasaki disease in the risk period after any NIP vaccination combination. The incidence rates will aid in the interpretation of clinical trials and post-marketing surveillance of new vaccines. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Kawasaki Disease Presenting as Acute Intestinal Obstruction

PubMed Central

Lone, Yasir Ahmad; Menon, Jagadeesh; Menon, Prema; Vaiphei, Kim; Narasimha Rao, Katragadda Lakshmi; Thapa, Baburam; Gupta, Kirti

2017-01-01

Kawasaki disease (KD) is an acute febrile illness of childhood associated with vasculitis of medium-sized arteries especially the coronary arteries. Typical clinical features involving the skin, mucous surfaces, etc., occur sequentially over a few days. We report a rare presentation of KD as a surgical abdomen in a 2-year-old boy. Awareness of this presentation is important as it can otherwise lead to a delay in starting potentially life-saving intervention like intravenous immunoglobulins for cardiac complications kept cryptic by the manifest acute abdomen. PMID:28694577

[Clinical features and course of Kawasaki disease in central Tunisia: a study about 14 cases collected over a period of three years (2000-2002)].

PubMed

Chemli, Jalel; Kchaou, Habib; Amri, Fethi; Belkadhi, Adel; Essoussi, Ahmed Sahloul; Gueddiche, Neji; Harbi, Abdelaziz

2005-08-01

To analyze the clinical features and course of Kawasaki disease in central Tunisia. We studied retrospectively 14 cases of children with Kawasaki disease collected in tunisian center during three years (2000-2002). The study is about 11 boys and 3 girls (sex - ratio: 3.6/1) aged from 6 months to 8 years (mean age : 4 years). Twelve patients had at least 5 diagnostic criteria of the illness, the two others had an incomplete form. We noted cardiac complications in seven patients treated belatedly, beyond 10 days of progression, because of atypical clinical presentations. All patients had all a middle caliber coronary aneurysm that was complicated by a thrombus in three cases, associated with pericarditis and minimal mitral insufficiency in a case and with a cardiac rhythm disturbance (block of branch) in another case. Besides the cardiac complications, several other visceral manifestation could be noted: joint symptoms in five cases, GI tract symptomes in three cases, neuro-meningeal in two cases and urinary trad symptomes in two other cases. Specific treatment (aspirin with antiinflammatory dose and intravenous immune globulin (IVIG)) has been instituted in all patients. The course was favorable for 12 patients with fast regression of clinical manifestation and progressive normalisation of biologic values. Two patients did not respond to the initial IVIG treatment, and had to recense received an additional course of IGIV but without clinical nor biological improvement. These two patients were treated with corticosteroids. Cardiac lesions disappeared completely in all patients even for those with thrombosis and in patients with IVIG-resistant Kawasaki disease. Only one patient had kept neurologic sequellae: aphasia, bevavioral problemes and partial epilepsy. Kawasaki disease is not rare in our region. Incomplete or atypical presentations are frequent and are a source of diagnostic delay. Coronary aneurysm due to the delay of treatment often regresses even in patients

GM-CSF primes cardiac inflammation in a mouse model of Kawasaki disease

PubMed Central

McKenzie, Brent S.

2016-01-01

Kawasaki disease (KD) is the leading cause of pediatric heart disease in developed countries. KD patients develop cardiac inflammation, characterized by an early infiltrate of neutrophils and monocytes that precipitates coronary arteritis. Although the early inflammatory processes are linked to cardiac pathology, the factors that regulate cardiac inflammation and immune cell recruitment to the heart remain obscure. In this study, using a mouse model of KD (induced by a cell wall Candida albicans water-soluble fraction [CAWS]), we identify an essential role for granulocyte/macrophage colony-stimulating factor (GM-CSF) in orchestrating these events. GM-CSF is rapidly produced by cardiac fibroblasts after CAWS challenge, precipitating cardiac inflammation. Mechanistically, GM-CSF acts upon the local macrophage compartment, driving the expression of inflammatory cytokines and chemokines, whereas therapeutically, GM-CSF blockade markedly reduces cardiac disease. Our findings describe a novel role for GM-CSF as an essential initiating cytokine in cardiac inflammation and implicate GM-CSF as a potential target for therapeutic intervention in KD. PMID:27595596

Infliximab treatment of intravenous immunoglobulin-resistant Kawasaki disease

PubMed Central

Burns, Jane C.; Best, Brookie M.; Mejias, Asuncion; Mahony, Lynn; Fixler, David E.; Jafri, Hasan S.; Melish, Marian E.; Jackson, Mary Anne; Asmar, Basim I.; Lang, David J.; Connor, James D.; Capparelli, Edmund V.; Keen, Monica L.; Mamun, Khalid; Keenan, Gregory F.; Ramilo, Octavio

2010-01-01

Objective To test the safety, tolerability, and pharmacokinetics of the anti- TNF-α monoclonal antibody, infliximab, in subjects with intravenous immunoglobulin (IVIG)-resistant Kawasaki disease (KD). Study design We conducted a multicenter, randomized, prospective trial of second IVIG infusion (2 g/kg) versus infliximab (5 mg/kg) in 24 children with acute KD and fever following initial treatment with IVIG. Primary outcome measures were infliximab safety, tolerability, and pharmacokinetics. Secondary outcome measures were duration of fever and changes in markers of inflammation. Results Study drug infusions were associated with cessation of fever within 24 hours in 11 of 12 subjects treated with infliximab and 8 of 12 subjects retreated with IVIG. No infusion reactions or serious adverse events were attributed to either study drug. No significant differences were observed between treatment groups in the change from baseline for laboratory variables, fever, or echocardiographic assessment of coronary arteries. Conclusion Both infliximab and a second IVIG infusion were safe and well-tolerated in subjects with KD who were resistant to standard IVIG treatment. The optimal management of patients resistant to IVIG remains to be determined. PMID:18672254

A 3-month-old infant with atypical Kawasaki disease.

PubMed

Lertamornkitti, Nichkamol; Wangjirapan, Anchalee

2018-05-30

We report a 3-month-old girl who presented with high-grade fever for 3 days. Her initial physical examination was normal. Investigation showed abnormal white cells in her urine. She was diagnosed with a urinary tract infection and received an antibiotic for 1 day. After that, she developed a generalised maculopapular rash over her body. An adverse drug reaction from the antibiotic was suspected, and the patient was referred to our hospital. On admission, she still had fever and was irritable. She was diagnosed with sepsis and given another broad-spectrum antibiotic for 2 days. However, her fever still persisted. An additional thorough physical examination showed redness of her BCG inoculation scar. Consequently, a diagnosis of Kawasaki disease (KD) was made. After she received intravenous immunoglobulin, her fever diminished straight away. This case highlights an unusual manifestation of KD in an uncommonly young age group. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Association of Kawasaki disease with tropospheric wind patterns.

PubMed

Rodó, Xavier; Ballester, Joan; Cayan, Dan; Melish, Marian E; Nakamura, Yoshikazu; Uehara, Ritei; Burns, Jane C

2011-01-01

The causal agent of Kawasaki disease (KD) remains unknown after more than 40 years of intensive research. The number of cases continues to rise in many parts of the world and KD is the most common cause of acquired heart disease in childhood in developed countries. Analyses of the three major KD epidemics in Japan, major non-epidemic interannual fluctuations of KD cases in Japan and San Diego, and the seasonal variation of KD in Japan, Hawaii, and San Diego, reveals a consistent pattern wherein KD cases are often linked to large-scale wind currents originating in central Asia and traversing the north Pacific. Results suggest that the environmental trigger for KD could be wind-borne. Efforts to isolate the causative agent of KD should focus on the microbiology of aerosols.

Association of Kawasaki disease with tropospheric wind patterns

PubMed Central

Rodó, Xavier; Ballester, Joan; Cayan, Dan; Melish, Marian E.; Nakamura, Yoshikazu; Uehara, Ritei; Burns, Jane C.

2011-01-01

The causal agent of Kawasaki disease (KD) remains unknown after more than 40 years of intensive research. The number of cases continues to rise in many parts of the world and KD is the most common cause of acquired heart disease in childhood in developed countries. Analyses of the three major KD epidemics in Japan, major non-epidemic interannual fluctuations of KD cases in Japan and San Diego, and the seasonal variation of KD in Japan, Hawaii, and San Diego, reveals a consistent pattern wherein KD cases are often linked to large-scale wind currents originating in central Asia and traversing the north Pacific. Results suggest that the environmental trigger for KD could be wind-borne. Efforts to isolate the causative agent of KD should focus on the microbiology of aerosols. PMID:22355668

Management of Kawasaki disease

PubMed Central

Eleftheriou, D; Levin, M; Shingadia, D; Tulloh, R; Klein, NJ; Brogan, PA

2014-01-01

Kawasaki disease (KD) is an acute self-limiting inflammatory disorder, associated with vasculitis, affecting predominantly medium-sized arteries, particularly the coronary arteries. In developed countries KD is the commonest cause of acquired heart disease in childhood. The aetiology of KD remains unknown, and it is currently believed that one or more as yet unidentified infectious agents induce an intense inflammatory host response in genetically susceptible individuals. Genetic studies have identified several susceptibility genes for KD and its sequelae in different ethnic populations, including FCGR2A, CD40, ITPKC, FAM167A-BLK and CASP3, as well as genes influencing response to intravenous immunoglobulin (IVIG) and aneurysm formation such as FCGR3B, and transforming growth factor (TGF) β pathway genes. IVIG and aspirin are effective therapeutically, but recent clinical trials and meta-analyses have demonstrated that the addition of corticosteroids to IVIG is beneficial for the prevention of coronary artery aneurysms (CAA) in severe cases with highest risk of IVIG resistance. Outside of Japan, however, clinical scores to predict IVIG resistance perform suboptimally. Furthermore, the evidence base does not provide clear guidance on which corticosteroid regimen is most effective. Other therapies, including anti-TNFα, could also have a role for IVIG-resistant KD. Irrespective of these caveats, it is clear that therapy that reduces inflammation in acute KD, improves outcome. This paper summarises recent advances in the understanding of KD pathogenesis and therapeutics, and provides an approach for managing KD patients in the UK in the light of these advances. PMID:24162006

Diagnosis, Treatment, and Long-Term Management of Kawasaki Disease: A Scientific Statement for Health Professionals From the American Heart Association.

PubMed

McCrindle, Brian W; Rowley, Anne H; Newburger, Jane W; Burns, Jane C; Bolger, Anne F; Gewitz, Michael; Baker, Annette L; Jackson, Mary Anne; Takahashi, Masato; Shah, Pinak B; Kobayashi, Tohru; Wu, Mei-Hwan; Saji, Tsutomu T; Pahl, Elfriede

2017-04-25

Kawasaki disease is an acute vasculitis of childhood that leads to coronary artery aneurysms in ≈25% of untreated cases. It has been reported worldwide and is the leading cause of acquired heart disease in children in developed countries. To revise the previous American Heart Association guidelines, a multidisciplinary writing group of experts was convened to review and appraise available evidence and practice-based opinion, as well as to provide updated recommendations for diagnosis, treatment of the acute illness, and long-term management. Although the cause remains unknown, discussion sections highlight new insights into the epidemiology, genetics, pathogenesis, pathology, natural history, and long-term outcomes. Prompt diagnosis is essential, and an updated algorithm defines supplemental information to be used to assist the diagnosis when classic clinical criteria are incomplete. Although intravenous immune globulin is the mainstay of initial treatment, the role for additional primary therapy in selected patients is discussed. Approximately 10% to 20% of patients do not respond to initial intravenous immune globulin, and recommendations for additional therapies are provided. Careful initial management of evolving coronary artery abnormalities is essential, necessitating an increased frequency of assessments and escalation of thromboprophylaxis. Risk stratification for long-term management is based primarily on maximal coronary artery luminal dimensions, normalized as Z scores, and is calibrated to both past and current involvement. Patients with aneurysms require life-long and uninterrupted cardiology follow-up. These recommendations provide updated and best evidence-based guidance to healthcare providers who diagnose and manage Kawasaki disease, but clinical decision making should be individualized to specific patient circumstances. © 2017 American Heart Association, Inc.

Kawasaki syndrome in an adult: endomyocardial histology and ventricular function during acute and recovery phases of illness.

PubMed

Marcella, J J; Ursell, P C; Goldberger, M; Lovejoy, W; Fenoglio, J J; Weiss, M B

1983-08-01

Kawasaki syndrome, an acute systemic inflammatory illness of unknown origin usually affecting children, may develop into a serious illness complicated by coronary artery aneurysms or myocarditis. This report describes an adult with Kawasaki syndrome studied by right ventricular endomyocardial biopsy and cardiac catheterization during the acute and recovery phases of illness. The initial biopsy specimen showed acute myocarditis and was associated with hemodynamic evidence of biventricular dysfunction, a severely depressed left ventricular ejection fraction and global hypokinesia. With time, there was spontaneous and rapid resolution of the inflammatory cell infiltrate with concurrent return to normal myocardial function. Right ventricular endomyocardial biopsy studies early in the course of the cardiac disease associated with Kawasaki syndrome may correlate with ventricular function and may be useful for monitoring immunosuppressive therapy in patients with this syndrome.

Safety and Efficacy of Warfarin Therapy in Kawasaki Disease.

PubMed

Baker, Annette L; Vanderpluym, Christina; Gauvreau, Kimberly A; Fulton, David R; de Ferranti, Sarah D; Friedman, Kevin G; Murray, Jenna M; Brown, Loren D; Almond, Christopher S; Evans-Langhorst, Margaret; Newburger, Jane W

2017-10-01

To describe the safety and efficacy of warfarin for patients with Kawasaki disease and giant coronary artery aneurysms (CAAs, ≥8 mm). Giant aneurysms are managed with combined anticoagulation and antiplatelet therapies, heightening risk of bleeding complications. We reviewed the time in therapeutic range; percentage of international normalization ratios (INRs) in range (%); bleeding events, clotting events; INRs ≥6; INRs ≥5 and <6; and INRs <1.5. In 9 patients (5 male), median age 14.4 years (range 7.1-22.8 years), INR testing was prescribed weekly to monthly and was done by home monitor (n = 5) or laboratory (n = 3) or combined (1). Median length of warfarin therapy was 7.2 years (2.3-13.3 years). Goal INR was 2.0-3.0 (n = 6) or 2.5-3.5 (n = 3), based on CAA size and history of CAA thrombosis. All patients were treated with aspirin; 1 was on dual antiplatelet therapy and warfarin. The median time in therapeutic range was 59% (37%-85%), and median percentage of INRs in range was 68% (52%-87%). INR >6 occurred in 3 patients (4 events); INRs ≥5 <6 in 7 patients (12 events); and INR <1.5 in 5 patients (28 events). The incidence of major bleeding events and clinically relevant nonmajor bleeding events were each 4.3 per 100 patient-years (95% CI 0.9-12.6). New asymptomatic coronary thrombosis was detected by imaging in 2 patients. Bleeding and clotting complications are common in patients with Kawasaki disease on warfarin and aspirin, with INRs in range only two-thirds of the time. Future studies should evaluate the use of direct oral anticoagulants in children as an alternative to warfarin. Copyright © 2017 Elsevier Inc. All rights reserved.

Coronary artery dilatation and vasculitis in a case of rabies: similarity with Kawasaki disease?

PubMed

Boukas, Ibtissama; Dahdah, Nagib; Robitaille, Yves; Fournier, Anne

2013-04-01

A 9-year-old boy died of rabies complications. We report the unusual combination between rabies, coronary dilatation on echocardiography and coronary vasculitis documented upon autopsy. In the search for the etiological agent of Kawasaki disease, we suggest that a viral infection with potential antigenic similarities to rabies virus should be entertained. © 2013 The Authors. Pediatrics International © 2013 Japan Pediatric Society.

Recurrent Kawasaki disease: USA and Japan.

PubMed

Maddox, Ryan A; Holman, Robert C; Uehara, Ritei; Callinan, Laura S; Guest, Jodie L; Schonberger, Lawrence B; Nakamura, Yosikazu; Yashiro, Mayumi; Belay, Ermias D

2015-12-01

Descriptive epidemiologic studies of recurrent and non-recurrent Kawasaki disease (KD) may identify other potentially important differences between these illnesses. Data from the USA and Japan, the Centers for Disease Control and Prevention (CDC) national KD surveillance(1984-2008) and the 17th Japanese nationwide survey (2001-2002), respectively, were analyzed to examine recurrent KD patients <18 years of age meeting the CDC KD case or atypical KD case definition. These patients were compared with non-recurrent KD patients. Of the 5557 US KD patients <18 years of age during 1984-2008, 97 (1.7%) were identified as having had recurrent KD. Among the US Asian/Pacific Islander KD patients, 3.5% had recurrent KD, which was similar to the percentage identified among KD patients (3.5%) in the Japanese survey. Compared with non-recurrent KD patients, KD patients [with recurrent KD] were more likely to be older, fulfill the atypical KD case definition, and have coronary artery abnormalities (CAA) despite i.v. immunoglobulin (IVIG) treatment. Differences in the age, race, and frequency of CAA exist between recurrent and non-recurrent KD patients. The increased association of CAA with recurrent KD suggests that more aggressive treatment strategies in conjunction with IVIG may be indicated for the second episode of KD. © 2015 Japan Pediatric Society.

Losartan attenuates the coronary perivasculitis through its local and systemic anti-inflammatory properties in a murine model of Kawasaki disease.

PubMed

Suganuma, Eisuke; Niimura, Fumio; Matsuda, Shinichi; Ukawa, Toshiko; Nakamura, Hideaki; Sekine, Kaori; Kato, Masahiko; Aiba, Yuji; Koga, Yasuhiro; Hayashi, Kuniyoshi; Takahashi, Osamu; Mochizuki, Hiroyuki

2017-04-01

Kawasaki disease is a common systemic vasculitis that leads to coronary artery lesions. Besides its antihypertensive effects, losartan can modulate inflammation in cardiovascular disease. We examined whether losartan can attenuate coronary inflammation in a murine model of Kawasaki disease. Five-wk-old C57/BL6J male mice were intraperitoneally injected with Lactobacillus casei cell wall extract to induce coronary inflammation and divided into four groups: placebo, intravenous immunoglobulin (IVIG), losartan, and IVIG+losartan. After 2 wk, mice were harvested. The coronary perivasculitis was significantly attenuated by losartan but not by IVIG alone, and further dramatic attenuation by IVIG+losartan was observed. The frequency of Lactobacillus casei cell wall extract-induced myocarditis (80%) was markedly lowered by losartan (22%) and IVIG+losartan (0%). Furthermore, interleukin (IL)-6 mRNA was markedly attenuated by IVIG+losartan. Serum levels of IL-6, TNF-α, MCP-1, and IL-10 after Lactobacillus casei cell wall extract injection were slightly decreased by IVIG or losartan. Moreover, IL-1β, IL-10, and MCP-1 levels were significantly decreased by IVIG+losartan. The addition of losartan to IVIG strongly attenuated the severity of coronary perivasculitis and the incidence of myocarditis, along with suppressing systemic/local cytokines as well as the activated macrophage infiltration. Therefore, losartan may be a potentially useful additive drug for the acute phase of Kawasaki disease to minimize coronary artery lesions.

Septated pericarditis associated with Kawasaki disease: a brief case report.

PubMed

Sonçaği, Arzu; Devrim, Ilker; Karagöz, Tevfik; Dilber, Embiya; Celiker, Alpay; Ozen, Seza; Seçmeer, Gülten

2007-01-01

Kawasaki disease (KD) is primarily the systemic vasculitis of childhood that affects mainly the medium-sized arteries, such as the coronary arteries. KD is the leading cause of acquired heart disease, whereas the incidence of rheumatic fever has declined. The most serious complication is coronary artery involvement. Among the children with KD who developed cardiac complications, pericarditis is a rare complication, with an incidence of 0.07%. We report our experience in a 5.5-year-old child with KD complicated with aneurysm of the left anterior descendant coronary artery and septated pericardial effusion, which has not been reported in the literature. The pericardial effusion disappeared very dramatically with intravenous immunoglobulin (IVIG) therapy. We would like to point out that septated pericardial effusion in cases of KD do not need any further therapy other than IVIG and high-dose acetylsalicylic acid.

Tricuspid and mitral regurgitation detected by color flow Doppler in the acute phase of Kawasaki disease

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

Suzuki, A.; Kamiya, T.; Tsuchiya, K.

Valvular lesions in the acute phase of Kawasaki disease were studied in 19 children. The patients were intensively observed by color flow Doppler every day from the day of hospitalization up to 12 days after the onset of the disease and 2 or more times a week thereafter, for up to 28 days. Mitral regurgitation (MR) was found in 9 patients (47%) and tricuspid regurgitation (TR) in 10 (53%). MRs were of transient type and confirmed from 7.5 +/- 1.6 (mean +/- standard deviation) to 13.1 +/- 6.5 days after the onset of the disease. Both types of valvular regurgitationmore » were mild. The direction of regurgitation was from the center of valvular coaptation toward the posterior wall of the atrium. Neither valvular prolapse nor valvular deformity was noted. In patients with MR, left ventricular ejection fraction on M-mode echocardiography was significantly lower in the acute phase than in the convalescent phase of the disease (p less than 0.05). Using gallium-67 scintigram, the positive uptake of the isotope was noted in 7 (88%) of 8 patients with MR, but not found at all in 8 patients free of MR. These results suggest that MR and TR are often transient in the acute phase of Kawasaki disease and could be attributed to myocarditis.« less

Fever without a source: evolution of a diagnosis from Kawasaki disease to acute myelogenous leukaemia.

PubMed

Lee, Begem; Kofman, Christine D; Tremoulet, Adriana H; Kuo, Dennis John

2017-05-06

A previously healthy 11-month-old male patient presented with fever, abdominal pain and irritability. As part of an extensive evaluation for the cause of his fevers, an echocardiogram was performed and showed mildly dilated coronary arteries, leading to a diagnosis of incomplete Kawasaki disease (KD). He was treated with intravenous immunoglobulin (IVIG), defervesced and was discharged home. Two weeks later, he presented with anaemia initially attributed to haemolytic anaemia secondary to IVIG and received a red blood cell transfusion. However, his anaemia recurred 2  weeks later with leucocytosis, prompting a bone marrow aspirate 4  weeks after his diagnosis of KD. This demonstrated acute myelogenous leukaemia most consistent with acute megakaryocytic leukaemia. This case highlights the potentially subtle presentation of acute leukaemia and the need to keep an open mind and reconsider the initial diagnosis as new information comes to light in the care of an ill child. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Acute Kawasaki disease with emphasis on the echocardiographic profile: A single center experience

PubMed Central

Hamza, Hala S.; Zaher, Asmaa Z.; Agha, Hala M.

Background: Echocardiographic features of acute Kawasaki disease (KD) have not been well characterized in Egyptian children. This study aimed to provide insight into the pattern of cardiac involvement in Egyptian children with Kawasaki disease, focusing on echocardiographic coronary abnormalities and their associated risk predictors. Methods and Results: Medical records of 64 KD patients from 2012 to 2016 were retrospectively analyzed with recalculation of coronary artery z-scores during the first eight weeks after fever onset. All patients received intravenous immunoglobulin (IVIG) and 57.8% were treated within 10 days of illness onset. Coronary abnormalities were found in 53.1% of all patients, and in 43.2% of those who received IVIG within 10 days. Giant aneurysms (z-score>10) comprised 23.5% of all coronary abnormalities. Coronary thrombosis occurred in two patients (5%), both of whom developed myocardial infarction, and one succumbed to heart failure with eventual in-hospital death. Overall, 7% of patients had mitral regurgitation (n = 5), 1.5% had aortic regurgitation (n = 1), and 7.8% had pericardial effusion (n = 5). Among a number of laboratory and clinical predictors, platelet count had the strongest association with coronary abnormalities (Area under Receiver-operating characteristic (ROC) curve: 0.794; 95% confidence interval 0.678–0.910; P < 0.001). Conclusion: Coronary abnormalities occur in a substantial percentage of KD in Egypt, with associated evidence of severe inflammation. Further efforts are required to increase awareness of the disease and to emphasize the importance of early IVIG administration. Future studies should also be undertaken to characterize the long term progression profile of the disease as well as the possible genetic background of the disease in Egypt. PMID:29564348

Recurrent Kawasaki disease, United States and Japan

PubMed Central

Maddox, Ryan A.; Holman, Robert C.; Uehara, Ritei; Callinan, Laura S.; Guest, Jodie L.; Schonberger, Lawrence B.; Nakamura, Yosikazu; Yashiro, Mayumi; Belay, Ermias D.

2015-01-01

Background Descriptive epidemiologic studies of recurrent and non-recurrent Kawasaki disease (KD) may identify other potentially important differences between these illnesses. Methods Data from the United States and Japan, the Centers for Disease Control and Prevention (CDC) national KD surveillance (1984–2008) and the 17th Japanese nationwide survey (2001–2002), respectively, were analyzed to examine recurrent KD patients <18 years of age meeting the CDC KD case or atypical KD case definition. These patients were compared to non-recurrent KD patients. Results Of the 5557 US KD patients <18 years of age during 1984–2008, 97 (1.7%) were identified as having had recurrent KD. Among the US Asian/Pacific Islander KD patients, 3.5% had recurrent KD, which was similar to the percentage identified among KD patients (3.5%) in the Japanese survey. Compared to non-recurrent KD patients, KD patients experiencing a recurrent KD episode were more likely to be older, fulfill the atypical KD case definition, and have coronary artery abnormalities (CAA) despite IVIG treatment. Conclusions Differences in the age, race, and frequency of CAA exist between recurrent and non-recurrent KD patients. The increased association of CAA with recurrent KD suggests that more aggressive treatment strategies in conjunction with IVIG may be indicated for the second episode of KD. PMID:26096590

Hemodynamic simulations in coronary aneurysms of a patient with Kawasaki Disease

NASA Astrophysics Data System (ADS)

Sengupta, Dibyendu; Marsden, Alison; Burns, Jane

2010-11-01

Kawasaki Disease is the leading cause of acquired pediatric heart disease, and can cause large coronary artery aneurysms in untreated cases. A simulation case study has been performed for a 10-year-old male patient with coronary aneurysms. Specialized coronary boundary conditions along with a lumped parameter heart model mimic the interactions between the ventricles and the coronary arteries, achieving physiologic pressure and flow waveforms. Results show persistent low shear stress in the aneurismal regions, and abnormally high shear at the aneurysm neck. Correlation functions have been derived to compare wall shear stress and wall shear stress gradients with recirculation time with the idea of localizing zones of calcification and thrombosis. Results are compared with those of an artificially created normal coronary geometry for the same patient. The long-term goal of this work is to develop links between hemodynamics and thrombotic risk to assist in clinical decision-making.

Predicting Coronary Artery Aneurysms in Kawasaki Disease at a North American Center: An Assessment of Baseline z Scores.

PubMed

Son, Mary Beth F; Gauvreau, Kimberlee; Kim, Susan; Tang, Alexander; Dedeoglu, Fatma; Fulton, David R; Lo, Mindy S; Baker, Annette L; Sundel, Robert P; Newburger, Jane W

2017-05-31

Accurate risk prediction of coronary artery aneurysms (CAAs) in North American children with Kawasaki disease remains a clinical challenge. We sought to determine the predictive utility of baseline coronary dimensions adjusted for body surface area ( z scores) for future CAAs in Kawasaki disease and explored the extent to which addition of established Japanese risk scores to baseline coronary artery z scores improved discrimination for CAA development. We explored the relationships of CAA with baseline z scores; with Kobayashi, Sano, Egami, and Harada risk scores; and with the combination of baseline z scores and risk scores. We defined CAA as a maximum z score (zMax) ≥2.5 of the left anterior descending or right coronary artery at 4 to 8 weeks of illness. Of 261 patients, 77 patients (29%) had a baseline zMax ≥2.0. CAAs occurred in 15 patients (6%). CAAs were strongly associated with baseline zMax ≥2.0 versus <2.0 (12 [16%] versus 3 [2%], respectively, P <0.001). Baseline zMax ≥2.0 had a C statistic of 0.77, good sensitivity (80%), and excellent negative predictive value (98%). None of the risk scores alone had adequate discrimination. When high-risk status per the Japanese risk scores was added to models containing baseline zMax ≥2.0, none were significantly better than baseline zMax ≥2.0 alone. In a North American center, baseline zMax ≥2.0 in children with Kawasaki disease demonstrated high predictive utility for later development of CAA. Future studies should validate the utility of our findings. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Sociodemographic profile of children with Kawasaki disease in North India.

PubMed

Prakash, Jeya; Singh, Surjit; Gupta, Anju; Bharti, Bhavneet; Bhalla, A K

2016-03-01

Kawasaki disease (KD) is now the commonest cause of acquired heart disease in children in developed countries. KD occurs all over the world, including developing countries. The present study steps out to explore our hypothesis, driven by clinical observation over the last 18 years, whether children with KD in North India are of a higher socioeconomic status than children with other rheumatologic diseases. One hundred consecutive children with KD, registered in Pediatric Rheumatology Clinic before January 2011, were enrolled as cases. Children with other rheumatologic diseases were taken as controls. Assessment of socioeconomic status was done by administering the Aggarwal scale. Data were collected through interview. Statistical analysis was done using SPSS package version 16. On univariate analysis, male sex, higher educational status of parents, urban residence, immunization status being complete, and higher scores on Aggarwal scale were found to be significantly associated with KD. On multivariate analysis, only male sex and urban residence were found to be significantly associated with KD (p < 0.001). Families of children with KD tend to have a better sociodemographic profile when compared with other pediatric rheumatologic disorders in North India. These results, however, need to be replicated in a multicentric study for any firm conclusions to be drawn.

Hemodynamic Based Coronary Artery Aneurysm Thrombosis Risk Stratification in Kawasaki Disease Patients

NASA Astrophysics Data System (ADS)

Grande Gutierrez, Noelia; Mathew, M.; McCrindle, B.; Kahn, A.; Burns, J.; Marsden, A.

2017-11-01

Coronary artery aneurysms (CAA) as a result of Kawasaki Disease (KD) put patients at risk for thrombosis and myocardial infarction. Current AHA guidelines recommend CAA diameter >8 mm or Z-score >10 as the criterion for initiating systemic anticoagulation. Our hypothesis is that hemodynamic data derived from computational blood flow simulations is a better predictor of thrombosis than aneurysm diameter alone. Patient-specific coronary models were constructed from CMRI for a cohort of 10 KD patients (5 confirmed thrombosis cases) and simulations with fluid structure interaction were performed using the stabilized finite element Navier-Stokes solver available in SimVascular. We used a closed-loop lumped parameter network (LPN) to model the heart and vascular boundary conditions coupled numerically to the flow solver. An automated parameter estimation method was used to match LPN values to clinical data for each patient. Hemodynamic data analysis resulted in low correlation between Wall Shear Stress (WSS)/ Particle Residence Time (PRT) and CAA diameter but demonstrates the positive correlation between hemodynamics and adverse patient outcomes. Our results suggest that quantifying WSS and PRT should enable identification of regions at higher risk of thrombosis. We propose a quantitative method to non-invasively assess the abnormal flow in CAA following KD that could potentially improve clinical decision-making regarding anticoagulation therapy.

[Giant coronary aneurysms in infants with Kawasaki disease].

PubMed

Sánchez Andrés, Antonio; Salvador Mercader, Inmaculada; Seller Moya, Julia; Carrasco Moreno, José Ignacio

2017-08-01

Kawasaki disease (KD) is an acute vasculitis of unknown origin and predominant in males. The long-term effects of the disease depend on whether there are coronary lesions, particularly aneurysms. The prognosis of patients with giant aneurysms is very poor due to their natural progression to coronary thrombosis or severe obstructive lesions. A series of 8 cases is presented where the epidemiology and diagnostic methods are described. The treatment of the acute and long-term cardiovascular sequelae is also reviewed. A descriptive analysis was conducted on patients admitted to the Paediatric Cardiology Unit of La Fe University Hospital (Valencia) with KD and a coronary lesion. More than one artery was involved in all patients. Although early diagnosis was established in only two cases, none of the patients had severe impairment of ventricular function during the acute phase. Treatment included intravenous gammaglobulin and acetylsalicylic acid at anti-inflammatory doses during the acute phase. A combination of dual antiplatelet therapy and corticosteroids was given in cases of coronary thrombosis. The silent aneurysms continue to persist. KD is the most common cause of acquired heart disease in children. The delay in diagnosis is associated with a greater likelihood of coronary lesions that could increase the risk of cardiovascular events in adulthood. Thus, this subgroup requires close clinical monitoring for a better control of cardiovascular risk factors over time. Copyright © 2016 Asociación Española de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.

Juvenile polyarteritis nodosa associated with toxoplasmosis presenting as Kawasaki disease.

PubMed

Başaran, Özge; Çakar, Nilgün; Gür, Gökçe; Kocabaş, Abdullah; Gülhan, Belgin; Çaycı, Fatma Şemsa; Çelikel, Banu Acar

2014-04-01

Polyarteritis nodosa (PAN) is a vasculitis characterized by inflammatory necrosis of medium-sized arteries. Juvenile PAN and Kawasaki disease (KD) both cause vasculitis of the medium-sized arteries, and share common features. They have overlapping clinical features. Treatment should be managed according to the severity of symptoms and persistence of clinical manifestations. Herein is described the case of a 14-year-old boy first diagnosed with KD, who then fulfilled the criteria for juvenile PAN due to the development of severe myalgia, persistent fever, polyneuropathy and coronary arterial dilatation. He also had acute toxoplasmosis at the onset of vasculitis symptoms. The final diagnosis was of juvenile PAN associated with toxoplasmosis infection. Toxoplasma infection can be considered as an etiological agent for PAN and other vasculitis syndromes. Awareness of toxoplasmosis-related PAN facilitates early diagnosis, and instigation of appropriate treatment. © 2014 The Authors. Pediatrics International © 2014 Japan Pediatric Society.

Characteristics and Fate of Systemic Artery Aneurysm after Kawasaki Disease.

PubMed

Hoshino, Shinsuke; Tsuda, Etsuko; Yamada, Osamu

2015-07-01

To determine the long-term outcome of systemic artery aneurysms (SAAs) after Kawasaki disease (KD). We investigated the characteristics and the fate of SAAs in 20 patients using medical records and angiograms. The age of onset of KD ranged from 1 month to 20 months. The interval from the onset of KD to the latest angiogram ranged from 16 months to 24 years. The regression rate of peripheral artery aneurysm and the frequency of stenotic lesions were analyzed by the Kaplan-Meier method in 11 patients who had undergone initial angiography within 4 months. The mean duration of fever was 24 ± 12 days. All 20 patients had at least 1 symmetric pair of aneurysms in bilateral peripheral arteries, and 16 patients had multiple SAAs. The distributions of SAAs was as follows: brachial artery, 30; common iliac artery, 20; internal iliac artery, 21; abdominal aortic aneurysm, 7; and others, 29. The frequencies of regression of SAA and of the occurrence of stenotic lesions at 20 years after the onset of KD were 51% and 25%, respectively (n = 42). The diameter of all SAAs in the acute phase leading to stenotic lesions in the late period was >10 mm. SAAs occurred symmetrically and were multiple in younger infants and those with severe acute vasculitis. The fate of SAAs resembles that of coronary artery aneurysms, and depends on the diameter during the acute phase. Larger SAAs can lead to stenotic lesions in the late period. Copyright © 2015 Elsevier Inc. All rights reserved.

A Pilot Study Evaluating Cerebral Vasculitis in Kawasaki's Disease.

PubMed

Yeom, Jung Sook; Cho, Young Hye; Koo, Chung Mo; Jun, Jin Su; Park, Ji Sook; Park, Eun Sil; Seo, Ji-Hyun; Lim, Jae-Young; Woo, Hyang-Ok; Youn, Hee-Shang

2018-06-18

Cerebral vasculitis is thought to be a possible underlying mechanism of severe neurological complications of Kawasaki's disease (KD), such as cerebral infarct or aneurysm rupture. To evaluate the intracranial inflammatory response in patients with acute-stage KD, we measured the levels of cytokines (interleukin [IL]-6 and tumor necrosis factor [TNF]-α) and pentraxin-3 (PTX3) in the cerebrospinal fluid of patients with KD ( n  = 7) and compared the levels to those of the age- and sex-matched febrile control patients (bacterial meningitis [ n  = 5], enteroviral meningitis [ n  = 10], nonspecific viral illness without central nervous system involvement [ n  = 10]). PTX3 and TNF-α were rarely detected and only in trace concentration in KD, and the levels of IL-6 were not different from those of nonspecific viral illnesses. These mediators are not established biomarkers for cerebral vasculitis but might reflect vascular inflammation in various diseases including KD. Therefore, intracranial inflammation including vasculitis seems to be insignificant in our patients with KD. However, our results might be attributed to the fact that these patients lacked any clinical signs of cerebral or coronary vessel involvement. None of them underwent brain imaging. To clarify this issue, further studies involving patients with neurologic symptoms and proven involvement of cerebral vessels are needed. Georg Thieme Verlag KG Stuttgart · New York.

Seasonality of Kawasaki Disease: A Global Perspective

PubMed Central

Burns, Jane C.; Herzog, Lauren; Fabri, Olivia; Tremoulet, Adriana H.; Rodó, Xavier; Uehara, Ritei; Burgner, David; Bainto, Emelia; Pierce, David; Tyree, Mary; Cayan, Daniel

2013-01-01

Background Understanding global seasonal patterns of Kawasaki disease (KD) may provide insight into the etiology of this vasculitis that is now the most common cause of acquired heart disease in children in developed countries worldwide. Methods Data from 1970-2012 from 25 countries distributed over the globe were analyzed for seasonality. The number of KD cases from each location was normalized to minimize the influence of greater numbers from certain locations. The presence of seasonal variation of KD at the individual locations was evaluated using three different tests: time series modeling, spectral analysis, and a Monte Carlo technique. Results A defined seasonal structure emerged demonstrating broad coherence in fluctuations in KD cases across the Northern Hemisphere extra-tropical latitudes. In the extra-tropical latitudes of the Northern Hemisphere, KD case numbers were highest in January through March and approximately 40% higher than in the months of lowest case numbers from August through October. Datasets were much sparser in the tropics and the Southern Hemisphere extra-tropics and statistical significance of the seasonality tests was weak, but suggested a maximum in May through June, with approximately 30% higher number of cases than in the least active months of February, March and October. The seasonal pattern in the Northern Hemisphere extra-tropics was consistent across the first and second halves of the sample period. Conclusion Using the first global KD time series, analysis of sites located in the Northern Hemisphere extra-tropics revealed statistically significant and consistent seasonal fluctuations in KD case numbers with high numbers in winter and low numbers in late summer and fall. Neither the tropics nor the Southern Hemisphere extra-tropics registered a statistically significant aggregate seasonal cycle. These data suggest a seasonal exposure to a KD agent that operates over large geographic regions and is concentrated during winter

Seasonality of Kawasaki disease: a global perspective.

PubMed

Burns, Jane C; Herzog, Lauren; Fabri, Olivia; Tremoulet, Adriana H; Rodó, Xavier; Uehara, Ritei; Burgner, David; Bainto, Emelia; Pierce, David; Tyree, Mary; Cayan, Daniel

2013-01-01

Understanding global seasonal patterns of Kawasaki disease (KD) may provide insight into the etiology of this vasculitis that is now the most common cause of acquired heart disease in children in developed countries worldwide. Data from 1970-2012 from 25 countries distributed over the globe were analyzed for seasonality. The number of KD cases from each location was normalized to minimize the influence of greater numbers from certain locations. The presence of seasonal variation of KD at the individual locations was evaluated using three different tests: time series modeling, spectral analysis, and a Monte Carlo technique. A defined seasonal structure emerged demonstrating broad coherence in fluctuations in KD cases across the Northern Hemisphere extra-tropical latitudes. In the extra-tropical latitudes of the Northern Hemisphere, KD case numbers were highest in January through March and approximately 40% higher than in the months of lowest case numbers from August through October. Datasets were much sparser in the tropics and the Southern Hemisphere extra-tropics and statistical significance of the seasonality tests was weak, but suggested a maximum in May through June, with approximately 30% higher number of cases than in the least active months of February, March and October. The seasonal pattern in the Northern Hemisphere extra-tropics was consistent across the first and second halves of the sample period. Using the first global KD time series, analysis of sites located in the Northern Hemisphere extra-tropics revealed statistically significant and consistent seasonal fluctuations in KD case numbers with high numbers in winter and low numbers in late summer and fall. Neither the tropics nor the Southern Hemisphere extra-tropics registered a statistically significant aggregate seasonal cycle. These data suggest a seasonal exposure to a KD agent that operates over large geographic regions and is concentrated during winter months in the Northern Hemisphere extra-tropics.

Parental anxiety associated with Kawasaki disease in previously healthy children.

PubMed

Chahal, Nita; Clarizia, Nadia A; McCrindle, Brian W; Boydell, Katherine M; Obadia, Maya; Manlhiot, Cedric; Dillenburg, Rejane; Yeung, Rae S M

2010-01-01

The objective of this study was to explore the lived experience of parents of children diagnosed with Kawasaki disease (KD) and to identify factors associated with increased levels of parental anxiety. Three focus groups were conducted including 25 parents of 17 patients with KD, seven (41%) of whom had coronary artery complications. A conceptual model was developed to depict parental experiences and illustrate the key issues related to heightened anxiety. Themes identified included anxiety related to the child's sudden illness and delay in obtaining a correct diagnosis because of the lack of health care providers' awareness and knowledge regarding KD. Parents were frustrated by the lack of information available in lay language and the limited scientific knowledge regarding the long-term consequences of the disease. Parents also reported positive transformations and different perspective toward challenges in life. However, the parents of children with coronary artery complications expressed persistent anxiety even years after the acute phase of the illness due to the uncertainty of the long-term prognosis. There remains a critical need for richly textured research data on the perspective and experience of families of children with KD. Copyright 2010 National Association of Pediatric Nurse Practitioners. Published by Mosby, Inc. All rights reserved.

Innate immune responses following Kawasaki disease and toxic shock syndrome

PubMed Central

Messina, Nicole; Germano, Susie; Bonnici, Rhian; Freyne, Bridget; Cheung, Michael; Goldsmith, Greta; Kollmann, Tobias R.; Levin, Michael; Burgner, David; Curtis, Nigel

2018-01-01

The pathogenesis of Kawasaki disease (KD) remains unknown and there is accumulating evidence for the importance of the innate immune system in initiating and mediating the host inflammatory response. We compared innate immune responses in KD and toxic shock syndrome (TSS) participants more than two years after their acute illness with control participants to investigate differences in their immune phenotype. Toxic shock syndrome shares many clinical features with KD; by including both disease groups we endeavoured to explore changes in innate immune responses following acute inflammatory illnesses more broadly. We measured the in vitro production of interferon (IFN)-γ, tumour necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, IL-1 receptor antagonist (IL-1ra), and IL-10 following whole blood stimulation with toll-like receptor and inflammasome ligands in 52 KD, 20 TSS, and 53 control participants in a case-control study. Analyses were adjusted for age, sex, and unstimulated cytokine concentrations. Compared to controls, KD participants have reduced IL-1ra production in response to stimulation with double stranded RNA (geometric mean ratio (GMR) 0.37, 95% CI 0.15, 0.89, p = 0.03) and increased IL-6 production in response to incubation with Lyovec™ (GMR 5.48, 95% CI 1.77, 16.98, p = 0.004). Compared to controls, TSS participants have increased IFN-γ production in response to peptidoglycan (GMR 4.07, 95% CI 1.82, 9.11, p = 0.001), increased IL-1β production to lipopolysaccharide (GMR 1.64, 95% CI 1.13, 2.38, p = 0.01) and peptidoglycan (GMR 1.61, 95% CI 1.11, 2.33, p = 0.01), and increased IL-6 production to peptidoglycan (GMR 1.45, 95% CI 1.10, 1.92, p = 0.01). Years following the acute illness, individuals with previous KD or TSS exhibit a pro-inflammatory innate immune phenotype suggesting a possible underlying immunological susceptibility or innate immune memory. PMID:29447181

Innate immune responses following Kawasaki disease and toxic shock syndrome.

PubMed

Chen, Katherine Y H; Messina, Nicole; Germano, Susie; Bonnici, Rhian; Freyne, Bridget; Cheung, Michael; Goldsmith, Greta; Kollmann, Tobias R; Levin, Michael; Burgner, David; Curtis, Nigel

2018-01-01

The pathogenesis of Kawasaki disease (KD) remains unknown and there is accumulating evidence for the importance of the innate immune system in initiating and mediating the host inflammatory response. We compared innate immune responses in KD and toxic shock syndrome (TSS) participants more than two years after their acute illness with control participants to investigate differences in their immune phenotype. Toxic shock syndrome shares many clinical features with KD; by including both disease groups we endeavoured to explore changes in innate immune responses following acute inflammatory illnesses more broadly. We measured the in vitro production of interferon (IFN)-γ, tumour necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, IL-1 receptor antagonist (IL-1ra), and IL-10 following whole blood stimulation with toll-like receptor and inflammasome ligands in 52 KD, 20 TSS, and 53 control participants in a case-control study. Analyses were adjusted for age, sex, and unstimulated cytokine concentrations. Compared to controls, KD participants have reduced IL-1ra production in response to stimulation with double stranded RNA (geometric mean ratio (GMR) 0.37, 95% CI 0.15, 0.89, p = 0.03) and increased IL-6 production in response to incubation with Lyovec™ (GMR 5.48, 95% CI 1.77, 16.98, p = 0.004). Compared to controls, TSS participants have increased IFN-γ production in response to peptidoglycan (GMR 4.07, 95% CI 1.82, 9.11, p = 0.001), increased IL-1β production to lipopolysaccharide (GMR 1.64, 95% CI 1.13, 2.38, p = 0.01) and peptidoglycan (GMR 1.61, 95% CI 1.11, 2.33, p = 0.01), and increased IL-6 production to peptidoglycan (GMR 1.45, 95% CI 1.10, 1.92, p = 0.01). Years following the acute illness, individuals with previous KD or TSS exhibit a pro-inflammatory innate immune phenotype suggesting a possible underlying immunological susceptibility or innate immune memory.

Comparative Effectiveness of Intravenous Immunoglobulin for Children with Kawasaki Disease: A Nationwide Cohort Study

PubMed Central

Lin, Ming-Chih; Fu, Yun-Ching; Jan, Sheng-Ling; Lai, Mei-Shu

2013-01-01

Introduction Different immunoglobulin manufacturing processes may influence its effectiveness for Kawasaki disease. However, nationwide studies with longitudinal follow-up are still lacking. The aim of this study was to evaluate the comparative effectiveness of immunoglobulin preparations from a nationwide perspective. Materials and Methods This is a nationwide retrospective cohort study with a new user design. Data came from the National Health Insurance Research Database of Taiwan. From 1997 to 2008, children under 2 years old who received immunoglobulin therapy for the first time under the main diagnosis of Kawasaki disease were enrolled. The manufacturing processes were divided into β-propiolactonation, acidification and those containing IgA. The endpoints were immunoglobulin non-responsiveness, acute aneurysm, prolonged use of anti-platelets or anti-coagulants, and recurrence. Results In total, 3830 children were enrolled. β-propiolactonation had a relative risk of 1.45 (95% CI 1.08∼1.94) of immunoglobulin non-responsiveness, however, the relative risks for acidification and containing IgA were non-significant. For acute aneurysms, acidification had a relative risk of 1.49 (95% CI 1.17∼1.90), however the relative risks for β-propiolactonation and containing IgA were non-significant. For prolonged use of anti-platelets or anti-coagulants, β-propiolactonation had a relative risk of 1.44 (95% CI 1.18∼1.76), and acidification protected against them both with a relative risk of 0.82 (95% CI 0.69∼0.97), whereas the relative risk for containing IgA was non-significant. For recurrence, all three factors were non-significant. Conclusions The effectiveness of immunoglobulin may differ among different manufacturing processes. β-propiolactonation had a higher risk of treatment failure and prolonged use of anti-platelets or anti-coagulants. Acidification may increase the risk of acute coronary aneurysms. PMID:23650564

Kawasaki disease with G6PD deficiency--report of one case and literature review.

PubMed

Chen, Chia-Hao; Lin, Li-Yan; Yang, Kuender D; Hsieh, Kai-Sheng; Kuo, Ho-Chang

2014-06-01

Kawasaki disease (KD) is a systemic vasculitis primarily affecting children who are younger than 5 years. The most serious complications are coronary artery aneurysms and sequelae of vasculitis with the subsequent development of coronary artery aneurysm. According to the literature, intravenous immunoglobulin (IVIG) plus high-dose aspirin (acetylsalicylic acid) were standard treatment for KD, whereas low-dose aspirin (3-5 mg/kg/day) was used for thrombocytosis in KD via antiplatelet effect. However, aspirin has been reported to have hemolytic potential in individuals with glucose-6-phosphate dehydrogenase (G6PD) deficiency. We report a child with G6PD-deficiency who has KD, and review the literature. Copyright © 2012. Published by Elsevier B.V.

Coronary artery aneurysm regression after Kawasaki disease and associated risk factors: a 3-year follow-up study in East China.

PubMed

Tang, Yunjia; Yan, Wenhua; Sun, Ling; Xu, Qiuqin; Ding, Yueyue; Lv, Haitao

2018-01-12

Kawasaki disease (KD) is the leading cause of acquired heart disease due to its complicated coronary artery lesions. Up to now, few studies were focused on the status of persistent coronary artery aneurysms (CAA) in KD patients. The present study was designed to identify the coronary artery outcomes and seek the risk factors associated with the regression of CAA in KD patients. One hundred and twenty KD patients with CAA hospitalized in Children's Hospital of Soochow University from Jan 2008 to Dec 2013 were prospectively studied by a 3-year follow-up. Data regarding demographic, clinical, laboratory, and echocardiographic characteristics were documented and further analyzed. It was estimated that 39.2% of the patients had complete regression of CAA within 4 weeks, 59.2% within 8 weeks, and 70.0% within 16 weeks. No fatal cardiac events occurred. We found patients who aged ≤ 1 year, received initial intravenous immunoglobulin (IVIG) treatment after the 10th day of illness, and IVIG non-responders were associated with the regression of persistent CAA. The relative risks were 1.55, 1.87, and 1.88, respectively. Age, initial IVIG treatment, and IVIG response were risk factors of persistent CAA, and more attention should be paid on these patients.

Predicting the characteristics of the aetiological agent for Kawasaki disease from other paediatric infectious diseases in Japan.

PubMed

Nagao, Y; Urabe, C; Nakamura, H; Hatano, N

2016-02-01

Although Kawasaki disease (KD), which was first reported in the 1960s, is assumed to be infectious, its aetiological agent(s) remains unknown. We compared the geographical distribution of the force of infection and the super-annual periodicity of KD and seven other paediatric infectious diseases in Japan. The geographical distribution of the force of infection, which was estimated as the inverse of the mean patient age, was similar in KD and other paediatric viral infections. This similarity was due to the fact that the force of infection was determined largely by the total fertility rate. This finding suggests that KD shares a transmission route, i.e. sibling-to-sibling infection, with other paediatric infections. The super-annual periodicity, which is positively associated with the sum of an infectious disease's incubation period and infectious period, was much longer for KD and exanthema subitum than other paediatric infectious diseases. The virus for exanthema subitum is known to persist across the host's lifespan, which suggests that the aetiological agent for KD may also be capable of persistent infection. Taken together, these findings suggest that the aetiological agent for KD is transmitted through close contact and persists asymptomatically in most hosts.

Psoriasiform Eruptions During Kawasaki Disease: A Distinct Phenotype

PubMed Central

Haddock, Ellen S.; Calame, Antoanella; Shimizu, Chisato; Tremoulet, Adriana H.; Burns, Jane C.; Tom, Wynnis L.

2016-01-01

Background A psoriasis-like eruption develops in a subset of patients with Kawasaki disease (KD). Objective To systematically compare KD-associated psoriasiform eruptions with classic psoriasis and the outcomes of KD in children with and without this rash. Methods This was a retrospective study of 11 KD cases with a psoriasiform eruption matched 1:2 by age, gender, and ethnicity with psoriasis-only and KD-only controls. Genotyping was performed in 10 cases for a deletion of two late cornified envelope (LCE) genes, LCE3C_LCE3B-del, associated with increased risk for pediatric-onset psoriasis. Results Similar to classic psoriasis, KD-associated eruptions were characterized clinically by well-demarcated, scaly pink plaques and histopathologically by intraepidermal neutrophils, suprabasilar keratin 16 expression, and increased Ki-67 expression. They showed less frequent diaper area involvement, more crust and serous exudate, and an enduring remission (91% vs. 23% with confirmed resolution; p < 0.001). Frequency of LCE3C_LCE3B-del and major KD outcomes were similar between cases and controls. Limitations The study was limited by the small number of cases, treatment variation, and availability of skin biopsy specimens. Conclusions Although the overall clinical and histopathologic findings were similar to conventional psoriasis, this appears to be a distinct phenotype with significantly greater propensity for remission. No adverse effect on KD outcomes was noted. PMID:26946987

Importance of anatomical dominance in the evaluation of coronary dilatation in Kawasaki disease.

PubMed

Dionne, Audrey; Hanna, Baher; Trinh Tan, Frédérick; Desjardins, Laurent; Lapierre, Chantale; Déry, Julie; Fournier, Anne; Dahdah, Nagib

2017-07-01

Introduction In Kawasaki disease, although coronary dilatation is attributed to vasculitis, the effect of myocardial inflammation is underestimated. Coronary dilatations are determined by Z-scores, which do not take into account dominance. The aim of the present study was to describe the impact of coronary dominance on dilatation in Kawasaki disease. We performed a retrospective analysis of coronary dilatations according to angiography categorisation of dominance. Of 28 patients (2.6 [0.2-10.1] years), right dominance was present in 15 patients and left in 13. Early dilatation was present in all patients, of whom 11 were ipsilateral to the dominant segment and 17 contralateral. Ipsilateral dilatations were present at diagnosis (9/11 versus 6/17, p=0.02) compared with contralateral dilatations, which developed 2 weeks after diagnosis (9/11 versus 16/17, p=0.29). Coronary artery Z-scores of patients with contralateral dilatation increased at 2 weeks, before returning to baseline values (2.0±2.2 at diagnosis, 4.1±1.8 at 2 weeks, 1.8±1.2 at 3-6 months, p=0.001), compared with patients with ipsilateral dilatation in whom Z-scores were maximal at diagnosis and remained stable (3.0±0.9, 2.7±1.1 and 2.6±1.5, respectively, p=0.13). Dominant coronary artery Z-scores were higher compared with non-dominant segments at diagnosis (3.0±0.9 versus 1.0±0.8, p<0.001) and at late follow-up (2.6±1.5 versus 0.4±1.4, p=0.002) in patients with ipsilateral dilatation. Progression of coronary dilatation after diagnosis may be a sign of dilatation secondary to vasculitis, as opposed to regression of Z-scores in ipsilateral dilatations, probably related to physiological vasodilatation in response to carditis. This needs to be validated in larger studies against vasculitic and myocardial inflammatory markers.

A 5-year-old boy with only fever and giant coronary aneurysms: the enigma of Kawasaki disease?

PubMed

Vignesh, Pandiarajan; Bhattad, Sagar; Singhal, Manphool; Singh, Surjit

2016-08-01

Epidemiological case definition of Kawasaki disease (KD) by the American Heart Association requires the presence of fever and four of the following: eye signs, oral mucosal changes, skin rashes, limb edema, and unilateral cervical lymphadenopathy. Incomplete KD is a well-known entity where there is lack of some of mucocutaneous features, and this occurs more often in infants. We report a 5-year-old boy with KD and giant coronary aneurysms, who presented only with fever and there is complete lack of skin and mucosal manifestations at presentation.

Assessment Of Coronary Artery Aneurysms Using Transluminal Attenuation Gradient And Computational Modeling In Kawasaki Disease Patients

NASA Astrophysics Data System (ADS)

Grande Gutierrez, Noelia; Kahn, Andrew; Shirinsky, Olga; Gagarina, Nina; Lyskina, Galina; Fukazawa, Ryuji; Owaga, Shunichi; Burns, Jane; Marsden, Alison

2015-11-01

Kawasaki Disease (KD) can result in coronary artery aneurysms (CAA) in up to 25% of patients, putting them at risk of thrombus formation, myocardial infarction and sudden death. Clinical guidelines recommend CAA diameter >8 mm as the arbitrary criterion for initiating systemic anticoagulation. KD patient specific modeling and flow simulations suggest that hemodynamic data can predict regions at increased risk of thrombosis. Transluminal Attenuation Gradient (TAG) is determined from the change in radiological attenuation per vessel length and has been proposed as a non-invasive method for characterizing coronary stenosis from CT Angiography. We hypothesized that CAA abnormal flow could be quantified using TAG. We computed hemodynamics for patient specific coronary models using a stabilized finite element method, coupled numerically to a lumped parameter network to model the heart and vascular boundary conditions. TAG was quantified in the major coronary arteries. We compared TAG for aneurysmal and normal arteries and we analyzed TAG correlation with hemodynamic and geometrical parameters. Our results suggest that TAG may provide hemodynamic data not available from anatomy alone. TAG represents a possible extension to standard CTA that could help to better evaluate the risk of thrombus formation in KD.

Diagnosis of systemic-onset juvenile idiopathic arthritis after treatment for presumed Kawasaki disease.

PubMed

Dong, Siwen; Bout-Tabaku, Sharon; Texter, Karen; Jaggi, Preeti

2015-05-01

To estimate the incidence of systemic-onset juvenile idiopathic arthritis (SoJIA) within 6 months after treatment for presumed Kawasaki disease (KD) (presumed patients with KD with subsequent diagnosis of SoJIA [pKD/SoJIA]) and describe presentation differences from sole KD. We identified patients treated for KD at Nationwide Children's Hospital and from the Pediatric Health Information System from 2009-2013. We then identified the subset of children, pKD/SoJIA, who received an International Classification of Diseases, Ninth Revision code for SoJIA and had it listed at least once 3 months after and within 6 months after KD diagnosis. Demographic characteristics, readmission rates, treatments, and complications were noted. A literature review was also performed to identify clinical, laboratory, and echocardiographic data of previously documented patients with KD later diagnosed with SoJIA. There were 6745 total treated patients with KD in the Pediatric Health Information System database during the study period; 10 patients were identified to have pKD/SoJIA (0.2% of cohort). Those with pKD/SoJIA were predominantly Caucasian compared with patients with KD (90% and 46.8%, respectively; P=.003). Macrophage activation syndrome was more common in patients with pKD/SoJIA than in sole patients with KD (30% and 0.30%, respectively; P<.001). Fifteen cases of pKD/SoJIA were identified by literature and chart review, 12 of whom were initially diagnosed with incomplete KD. We reported a 0.2% incidence of pKD/SoJIA, which was associated with Caucasian race, macrophage activation syndrome, and an incomplete KD phenotype. Copyright © 2015 Elsevier Inc. All rights reserved.

Resistance to intravenous immunoglobulin in children with Kawasaki disease

PubMed Central

Tremoulet, Adriana H.; Best, Brookie M.; Song, Sungchan; Wang, Susan; Corinaldesi, Elena; Eichenfield, Julia R.; Martin, Danielle D.; Newburger, Jane W.; Burns, Jane C.

2008-01-01

Objectives To explore the increased incidence of intravenous immunoglobulin (IVIG) resistance among San Diego County Kawasaki disease (KD) patients in 2006 and to evaluate a scoring system to predict IVIG-resistant patients with KD. Study design We performed a retrospective review of patients with KD treated within 10 days of fever onset. Using multivariate analysis, independent predictors of IVIG-resistance were combined into a scoring system. Results In 2006, 38.3 % of patients with KD in San Diego County were IVIG-resistant, a significant increase over previous years. IVIG-resistance was not associated with a particular brand or lot of IVIG. Resistant patients were diagnosed earlier, had higher % bands, and higher concentrations of C-reactive protein, alanine aminotransferase, and γ-glutamyl transferase (GGT). They also had lower platelet counts and age-adjusted hemoglobin (zHgb) concentrations and were more likely to have aneurysms (p=0.0008). A scoring system developed to predict IVIG-resistant patients using illness day, % bands, GGT, and zHgb, had a sensitivity of 73.3% and specificity of 61.9%. Conclusions An unexplained increase in IVIG-resistance was noted among patients with KD in San Diego County in 2006. Scoring systems based on demographic and laboratory data were insufficiently accurate to be clinically useful in our ethnically diverse population. PMID:18571548

Revisiting the role of environmental and climate factors on the epidemiology of Kawasaki disease.

PubMed

Rodó, Xavier; Ballester, Joan; Curcoll, Roger; Boyard-Micheau, Joseph; Borràs, Sílvia; Morguí, Josep-Anton

2016-10-01

Can environmental factors, such as air-transported preformed toxins, be of key relevance to the health outcomes of poorly understood human ailments (e.g., rheumatic diseases such as vasculitides, some inflammatory diseases, or even severe childhood acquired heart diseases)? Can the physical, chemical, or biological features of air masses be linked to the emergence of diseases such as Kawasaki disease (KD), Henoch-Schönlein purpura, Takayasu's aortitis, and ANCA-associated vasculitis? These diseases surprisingly share some common epidemiological features. For example, they tend to appear as clusters of cases grouped geographically and temporarily progress in nonrandom sequences that repeat every year in a similar way. They also show concurrent trend changes within regions in countries and among different world regions. In this paper, we revisit transdisciplinary research on the role of environmental and climate factors in the epidemiology of KD as a paradigmatic example of this group of diseases. Early-warning systems based on environmental alerts, if successful, could be implemented as a way to better inform patients who are predisposed to, or at risk for, developing KD. Further research on the etiology of KD could facilitate the development of vaccines and specific medical therapies. © 2016 New York Academy of Sciences.

N-terminal pro-brain natriuretic peptide in acute Kawasaki disease correlates with coronary artery involvement.

PubMed

Adjagba, Philippe M; Desjardins, Laurent; Fournier, Anne; Spigelblatt, Linda; Montigny, Martine; Dahdah, Nagib

2015-10-01

We have lately documented the importance of N-terminal pro-brain natriuretic peptide in aiding the diagnosis of Kawasaki disease. We sought to investigate the potential value of N-terminal pro-brain natriuretic peptide pertaining to the prediction of coronary artery dilatation (Z-score>2.5) and/or of resistance to intravenous immunoglobulin therapy. We hypothesised that increased serum N-terminal pro-brain natriuretic peptide level correlates with increased coronary artery dilatation and/or resistance to intravenous immunoglobulin. We carried out a prospective study involving newly diagnosed patients treated with 2 g/kg intravenous immunoglobulin within 5-10 days of onset of fever. Echocardiography was performed in all patients at onset, then weekly for 3 weeks, then at month 2, and month 3. Coronary arteries were measured at each visit, and coronary artery Z-score was calculated. All the patients had N-terminal pro-brain natriuretic peptide serum level measured at onset, and the Z-score calculated. There were 109 patients enrolled at 6.58±2.82 days of fever, age 3.79±2.92 years. High N-terminal pro-brain natriuretic peptide level was associated with coronary artery dilatation at onset in 22.2 versus 5.6% for normal N-terminal pro-brain natriuretic peptide levels (odds ratio 4.8 [95% confidence interval 1.05-22.4]; p=0.031). This was predictive of cumulative coronary artery dilatation for the first 3 months (p=0.04-0.02), but not during convalescence at 2-3 months (odds ratio 1.28 [95% confidence interval 0.23-7.3]; p=non-significant). Elevated N-terminal pro-brain natriuretic peptide levels did not predict intravenous immunoglobulin resistance, 15.3 versus 13.5% (p=1). Elevated N-terminal pro-brain natriuretic peptide level correlates with acute coronary artery dilatation in treated Kawasaki disease, but not with intravenous immunoglobulin resistance.

Elevation of Serum Acid Sphingomyelinase Activity in Acute Kawasaki Disease.

PubMed

Konno, Yuuki; Takahashi, Ikuko; Narita, Ayuko; Takeda, Osamu; Koizumi, Hiromi; Tamura, Masamichi; Kikuchi, Wataru; Komatsu, Akira; Tamura, Hiroaki; Tsuchida, Satoko; Noguchi, Atsuko; Takahashi, Tsutomu

2015-10-01

Kawasaki disease (KD) is an acute systemic vasculitis that affects both small and medium-sized vessels including the coronary arteries in infants and children. Acid sphingomyelinase (ASM) is a lysosomal glycoprotein that hydrolyzes sphingomyelin to ceramide, a lipid, that functions as a second messenger in the regulation of cell functions. ASM activation has been implicated in numerous cellular stress responses and is associated with cellular ASM secretion, either through alternative trafficking of the ASM precursor protein or by means of an unidentified mechanism. Elevation of serum ASM activity has been described in several human diseases, suggesting that patients with diseases involving vascular endothelial cells may exhibit a preferential elevation of serum ASM activity. As acute KD is characterized by systemic vasculitis that could affect vascular endothelial cells, the elevation of serum ASM activity should be considered in these patients. In the present study, serum ASM activity in the sera of 15 patients with acute KD was determined both before and after treatment with infusion of high-dose intravenous immunoglobulin (IVIG), a first-line treatment for acute KD. Serum ASM activity before IVIG was significantly elevated in KD patients when compared to the control group (3.85 ± 1.46 nmol/0.1 ml/6 h vs. 1.15 ± 0.10 nmol/0.1 ml/6 h, p < 0.001), suggesting that ASM activation may be involved in the pathophysiology of this condition. Serum ASM activity before IVIG was significantly correlated with levels of C-reactive protein (p < 0.05). These results suggest the involvement of sphingolipid metabolism in the pathophysiology of KD.

Hemodynamic simulations in coronary aneurysms of children with Kawasaki disease

NASA Astrophysics Data System (ADS)

Sengupta, Dibyendu; Burns, Jane; Marsden, Alison

2009-11-01

Kawasaki disease (KD) is a serious pediatric illness affecting the cardiovascular system. One of the most serious complications of KD, occurring in about 25% of untreated cases, is the formation of large aneurysms in the coronary arteries, which put patients at risk for myocardial infarction. In this project we performed patient specific computational simulations of blood flow in aneurysmal left and right coronary arteries of a KD patient to gain an understanding about their hemodynamics. Models were constructed from CT data using custom software. Typical pulsatile flow waveforms were applied at the model inlets, while resistance and RCR lumped models were applied and compared at the outlets. Simulated pressure waveforms compared well with typical physiologic data. High wall shear stress values are found in the narrow region at the base of the aneurysm and low shear values occur in regions of recirculation. A Lagrangian approach has been adopted to perform particle tracking and compute particle residence time in the recirculation. Our long-term goal will be to develop links between hemodynamics and the risk for thrombus formation in order to assist in clinical decision-making.

The Clinical Profile of Kawasaki Disease in Algerian Children: A Single Institution Experience.

PubMed

Boudiaf, Houda; Achir, Moussa

2016-04-01

Kawasaki disease (KD) in an acute vasculitis of unknown etiology. The epidemiological data available for Algerian patients remains insufficient. To describe the demographic, clinical features of children with KD and to identify the risk factors for developing coronary artery lesions (CAL). This retrospective study included children admitted with KD at the pediatric hospital in Algiers from January 2005 to December 2014. One hundred thirty-three patients (82 boys and 51 girls) with a mean age of 31 months were identified. The most common sign was fever, rash, oral changes and conjunctivitis. The cardiac complications were CAL (22.5%), pericarditis (2%) and myocarditis (1.5%). The independent variable for prediction of CAL was duration of fever >10 days, male gender and platelet count >450,000/mm3 CONCLUSION: The incidence of cardiovascular complications is high. Knowledge of KD among Algerian pediatricians should be enhanced to guarantee appropriate treatment of this disease. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Characterization of T cell repertoire changes in acute Kawasaki disease

PubMed Central

1993-01-01

Kawasaki disease (KD) is an acute multisystem vasculitis of unknown etiology that is associated with marked activation of T cells and monocyte/macrophages. Using a quantitative polymerase chain reaction (PCR) technique, we recently found that the acute phase of KD is associated with the expansion of T cells expressing the V beta 2 and V beta 8.1 gene segments. In the present work, we used a newly developed anti-V beta 2 monoclonal antibody (mAb) and studied a new group of KD patients to extend our previous PCR results. Immunofluorescence analysis confirmed that V beta 2-bearing T cells are selectively increased in patients with acute KD. The increase occurred primarily in the CD4 T cell subset. The percentages of V beta 2+ T cells as determined by mAb reactivity and flow cytometry correlated linearly with V beta expression as quantitated by PCR. However, T cells from acute KD patients appeared to express proportionately higher levels of V beta 2 transcripts per cell as compared with healthy controls or convalescent KD patients. Sequence analysis of T cell receptor beta chain genes of V beta 2 and V beta 8.1 expressing T cells from acute KD patients showed extensive junctional region diversity. These data showing polyclonal expansion of V beta 2+ and V beta 8+ T cells in acute KD provide additional insight into the immunopathogenesis of this disease. PMID:8094737

Whole blood transcriptional profiles as a prognostic tool in complete and incomplete Kawasaki Disease.

PubMed

Jaggi, Preeti; Mejias, Asuncion; Xu, Zhaohui; Yin, Han; Moore-Clingenpeel, Melissa; Smith, Bennett; Burns, Jane C; Tremoulet, Adriana H; Jordan-Villegas, Alejandro; Chaussabel, Damien; Texter, Karen; Pascual, Virginia; Ramilo, Octavio

2018-01-01

Early identification of children with Kawasaki Disease (KD) is key for timely initiation of intravenous immunoglobulin (IVIG) therapy. However, the diagnosis of the disease remains challenging, especially in children with an incomplete presentation (inKD). Moreover, we currently lack objective tools for identification of non-response (NR) to IVIG. Children with KD were enrolled and samples obtained before IVIG treatment and sequentially at 24 h and 4-6 weeks post-IVIG in a subset of patients. We also enrolled children with other febrile illnesses [adenovirus (AdV); group A streptococcus (GAS)] and healthy controls (HC) for comparative analyses. Blood transcriptional profiles were analyzed to define: a) the cKD and inKD biosignature, b) compare the KD signature with other febrile illnesses and, c) identify biomarkers predictive of clinical outcomes. We identified a cKD biosignature (n = 39; HC, n = 16) that was validated in two additional cohorts of children with cKD (n = 37; HC, n = 20) and inKD (n = 13; HC, n = 8) and was characterized by overexpression of inflammation, platelets, apoptosis and neutrophil genes, and underexpression of T and NK cell genes. Classifier genes discriminated KD from adenovirus with higher sensitivity and specificity (92% and 100%, respectively) than for GAS (75% and 87%, respectively). We identified a genomic score (MDTH) that was higher at baseline in IVIG-NR [median 12,290 vs. 5,572 in responders, p = 0.009] and independently predicted IVIG-NR. A reproducible biosignature from KD patients was identified, and was similar in children with cKD and inKD. A genomic score allowed early identification of children at higher risk for non-response to IVIG.

Classification of coronary artery tissues using optical coherence tomography imaging in Kawasaki disease

NASA Astrophysics Data System (ADS)

Abdolmanafi, Atefeh; Prasad, Arpan Suravi; Duong, Luc; Dahdah, Nagib

2016-03-01

Intravascular imaging modalities, such as Optical Coherence Tomography (OCT) allow nowadays improving diagnosis, treatment, follow-up, and even prevention of coronary artery disease in the adult. OCT has been recently used in children following Kawasaki disease (KD), the most prevalent acquired coronary artery disease during childhood with devastating complications. The assessment of coronary artery layers with OCT and early detection of coronary sequelae secondary to KD is a promising tool for preventing myocardial infarction in this population. More importantly, OCT is promising for tissue quantification of the inner vessel wall, including neo intima luminal myofibroblast proliferation, calcification, and fibrous scar deposits. The goal of this study is to classify the coronary artery layers of OCT imaging obtained from a series of KD patients. Our approach is focused on developing a robust Random Forest classifier built on the idea of randomly selecting a subset of features at each node and based on second- and higher-order statistical texture analysis which estimates the gray-level spatial distribution of images by specifying the local features of each pixel and extracting the statistics from their distribution. The average classification accuracy for intima and media are 76.36% and 73.72% respectively. Random forest classifier with texture analysis promises for classification of coronary artery tissue.

Suppressed plasmablast responses in febrile infants, including children with Kawasaki disease

PubMed Central

Martin, Meghan; Wrotniak, Brian H.

2018-01-01

Background Kawasaki disease (KD), the leading cause of acquired heart disease in children, primarily affects infants and toddlers. Investigations on immune responses during KD are hampered by a limited understanding of normal immune responses in these ages. It’s well known that Infants have poorer vaccine responses and difficulty with maintaining prolonged serum immunity, but there are few studies on human infants detailing immune deficiencies. Limited studies propose an inability to maintain life-long bone marrow plasma cells. Plasmablasts are a transitional cell form of B cells that lead to long-term Plasma cells. Plasmablasts levels rise in the peripheral blood after exposure to a foreign antigen. In adult studies, these responses are both temporally and functionally well characterized. To date, there have been few studies on plasmablasts in the predominant age range of KD. Methods Children presenting to an urban pediatric emergency room undergoing laboratory evaluation, who had concern of KD or had fever and symptoms overlapping those of KD, were recruited. Peripheral blood mononuclear cells were isolated and evaluated utilizing flow cytometry with specific B cell markers from 18 KD subjects and 69 febrile controls. Results Plasmablast numbers and temporal formation are similar between infectious disease controls and KD subjects. In both groups, infants have diminished plasmablast responses compared to older children. Conclusion In this single-time point survey, infants have a blunted peripheral plasmablast response. Overall, similar plasmablast responses in KD and controls support an infectious disease relationship to KD. Future time-course studies of plasmablasts in infants are warranted as this phenomenon may contribute to observed immune responses in this age group. PMID:29579044

Identification of candidate diagnostic serum biomarkers for Kawasaki disease using proteomic analysis

PubMed Central

Kimura, Yayoi; Yanagimachi, Masakatsu; Ino, Yoko; Aketagawa, Mao; Matsuo, Michie; Okayama, Akiko; Shimizu, Hiroyuki; Oba, Kunihiro; Morioka, Ichiro; Imagawa, Tomoyuki; Kaneko, Tetsuji; Yokota, Shumpei; Hirano, Hisashi; Mori, Masaaki

2017-01-01

Kawasaki disease (KD) is a systemic vasculitis and childhood febrile disease that can lead to cardiovascular complications. The diagnosis of KD depends on its clinical features, and thus it is sometimes difficult to make a definitive diagnosis. In order to identify diagnostic serum biomarkers for KD, we explored serum KD-related proteins, which differentially expressed during the acute and recovery phases of two patients by mass spectrometry (MS). We identified a total of 1,879 proteins by MS-based proteomic analysis. The levels of three of these proteins, namely lipopolysaccharide-binding protein (LBP), leucine-rich alpha-2-glycoprotein (LRG1), and angiotensinogen (AGT), were higher in acute phase patients. In contrast, the level of retinol-binding protein 4 (RBP4) was decreased. To confirm the usefulness of these proteins as biomarkers, we analyzed a total of 270 samples, including those collected from 55 patients with acute phase KD, by using western blot analysis and microarray enzyme-linked immunosorbent assays (ELISAs). Over the course of this experiment, we determined that the expression level of these proteins changes specifically in the acute phase of KD, rather than the recovery phase of KD or other febrile illness. Thus, LRG1 could be used as biomarkers to facilitate KD diagnosis based on clinical features. PMID:28262744

Epidemiologic survey of Kawasaki disease in Inner Mongolia, China, between 2001 and 2013

PubMed Central

Zhang, Xiaomei; Liang, Yanyan; Feng, Wanyu; Su, Xuewen; Zhu, Hua

2016-01-01

The epidemiologic features of Kawasaki disease (KD) in the Inner Mongolia Autonomous Region of China has not been previously determined, to the best of our knowledge. Therefore, the aim of the present study was to investigate the epidemiology of KD in Inner Mongolia. Clinical data from 518 patients treated for KD in Inner Mongolia between January 2001 and December 2013 were analyzed. The results indicated that the mean annual incidence rate was 3.55±2.96 per 100,000 children under the age of 5 years between 2001 and 2013. The age at diagnosis ranged between 49 days and 14 years, while the disease occurred more frequently in the spring and summer. In addition, the incidence of coronary artery lesion (CAL) was reported to be 40.2% in the present survey. KD patients in the Han Chinese ethnic group were more likely to be complicated by CAL, whereas patients with incidence of KD in July were less likely to be complicated by CAL. In conclusion, the incidence of KD was observed to be increasing in Inner Mongolia, while the ethnic group and month of onset may be associated with the incidence of CAL in KD patients. PMID:27446347

Can a systems biology approach unlock the mysteries of Kawasaki disease?

PubMed

Rowley, Anne H

2013-01-01

Kawasaki disease (KD) is a systemic inflammatory illness of childhood that particularly affects the coronary arteries. It can lead to coronary artery aneurysms, myocardial infarction, and sudden death. Clinical and epidemiologic data support an infectious cause, and the etiology remains unknown, but recent data support infection with a 'new' virus. Genetic factors influence KD susceptibility; the incidence is 10-fold higher in children of Asian when compared with Caucasian ethnicity. Recent research has identified genes affecting immune response that are associated with KD susceptibility and outcome. A re-examination of the pathologic features of KD has yielded a three process model of KD vasculopathy, providing a framework for understanding the KD arterial immune response and the damage it inflicts and for identifying new therapeutic targets for KD patients with coronary artery abnormalities. The researcher is faced with many challenges in determining the pathogenesis of KD. A systems biology approach incorporating genomics, proteomics, transcriptomics, and microbial bioinformatics analysis of high-throughput sequence data from KD tissues could provide the keys to unlocking the mysteries of this potentially fatal illness of childhood. Copyright © 2013 Wiley Periodicals, Inc.

An MBO Scheme for Minimizing the Graph Ohta-Kawasaki Functional

NASA Astrophysics Data System (ADS)

van Gennip, Yves

2018-06-01

We study a graph-based version of the Ohta-Kawasaki functional, which was originally introduced in a continuum setting to model pattern formation in diblock copolymer melts and has been studied extensively as a paradigmatic example of a variational model for pattern formation. Graph-based problems inspired by partial differential equations (PDEs) and variational methods have been the subject of many recent papers in the mathematical literature, because of their applications in areas such as image processing and data classification. This paper extends the area of PDE inspired graph-based problems to pattern-forming models, while continuing in the tradition of recent papers in the field. We introduce a mass conserving Merriman-Bence-Osher (MBO) scheme for minimizing the graph Ohta-Kawasaki functional with a mass constraint. We present three main results: (1) the Lyapunov functionals associated with this MBO scheme Γ -converge to the Ohta-Kawasaki functional (which includes the standard graph-based MBO scheme and total variation as a special case); (2) there is a class of graphs on which the Ohta-Kawasaki MBO scheme corresponds to a standard MBO scheme on a transformed graph and for which generalized comparison principles hold; (3) this MBO scheme allows for the numerical computation of (approximate) minimizers of the graph Ohta-Kawasaki functional with a mass constraint.

Kawasaki Disease With Coronary Artery Aneurysms: Psychosocial Impact on Parents and Children.

PubMed

Chahal, Nita; Jelen, Ahlexxi; Rush, Janet; Manlhiot, Cedric; Boydell, Katherine M; Sananes, Renee; McCrindle, Brian W

For those living with Kawasaki disease and coronary artery aneurysms, little is known about the psychosocial burden faced by parents and their children. Exploratory, descriptive, mixed-methods design examining survey and interview data about health-related uncertainty, intrusiveness, and self-efficacy. Parents' uncertainty was associated with missed diagnosis, higher income, and maternal education. Higher uncertainty scores among children were associated with absence of chest pain and lower number of echocardiograms. High intrusiveness scores among parents were associated with previous cardiac catheterization, use of anticoagulants, lower parent education and income, and missed diagnosis. High intrusiveness scores among children were associated with high paternal education. Children's total self-efficacy scores increased with chest pain and larger aneurysm size. Qualitative analysis showed two central themes: Psychosocial Struggle and Cautious Optimism. Negative illness impact is associated with a more intense medical experience and psychosocial limitations. Timely assessment and support are warranted to meet parents' and children's needs. Copyright © 2016 National Association of Pediatric Nurse Practitioners. Published by Elsevier Inc. All rights reserved.

Kawasaki disease in Sicily: clinical description and markers of disease severity.

PubMed

Maggio, Maria Cristina; Corsello, Giovanni; Prinzi, Eugenia; Cimaz, Rolando

2016-11-02

Kawasaki disease (KD) is an acute systemic vasculitis of small and middle size arteries; 15-25 % of untreated patients and 5 % of patients treated with intravenous immunoglobulin (IVIG) develop coronary artery lesions (CAL). Many studies tried to find the most effective treatment in the management of resistant KD and to select the risk factors for CAL. Our data are assessed on children from west Sicily, characterized by a genetic heterogeneity. We studied the clinical data of 70 KD Sicilian children (36 males: 51 %; 34 females: 49 %), analysed retrospectively, including: demographic and laboratory parameters; echocardiographic findings at diagnosis, at 2, 6 and 8 weeks, and at 1 year after the onset of the illness. Forty-seven had Typical KD, three Atypical KD and twenty Incomplete KD. Age at the disease onset ranged from 0.1 to 8.9 years. IVIG were administered 5 ± 2 days after the fever started. Defervescence occurred 39 ± 26 hours after the first IVIG infusion. Fifty-six patients (80 %) received 1 dose of IVIG (responders); 14 patients (20 %) had a resistant KD, with persistent fever after the first IVIG dose (non responders). Ten (14 %) non responders responded to the second dose, 4 (5 %) responded to three doses; one needed treatment with high doses of steroids and Infliximab. Cardiac involvement was documented in twenty-two cases (eighteen with transient dilatation/ectasia, fifteen with aneurysms). Pericardial effusion, documented in eleven, was associated with coronaritis and aneurysms, and was present earlier than coronary involvement in seven. Hypoalbuminemia, D-dimer pre-IVIG, gamma-GT pre-IVIG showed a statistically significant direct correlation with IVIG doses, highlighting the role of these parameters as predictor markers of refractory disease. The persistence of elevated CRP, AST, ALT levels, a persistent hyponatremia and hypoalbuminemia after IVIG therapy, also had a statistical significant correlation with IVIG doses. Non responders

Whole blood transcriptional profiles as a prognostic tool in complete and incomplete Kawasaki Disease

PubMed Central

Xu, Zhaohui; Yin, Han; Moore-Clingenpeel, Melissa; Smith, Bennett; Burns, Jane C.; Tremoulet, Adriana H.; Jordan-Villegas, Alejandro; Chaussabel, Damien; Texter, Karen; Pascual, Virginia; Ramilo, Octavio

2018-01-01

Background Early identification of children with Kawasaki Disease (KD) is key for timely initiation of intravenous immunoglobulin (IVIG) therapy. However, the diagnosis of the disease remains challenging, especially in children with an incomplete presentation (inKD). Moreover, we currently lack objective tools for identification of non-response (NR) to IVIG. Methods Children with KD were enrolled and samples obtained before IVIG treatment and sequentially at 24 h and 4–6 weeks post-IVIG in a subset of patients. We also enrolled children with other febrile illnesses [adenovirus (AdV); group A streptococcus (GAS)] and healthy controls (HC) for comparative analyses. Blood transcriptional profiles were analyzed to define: a) the cKD and inKD biosignature, b) compare the KD signature with other febrile illnesses and, c) identify biomarkers predictive of clinical outcomes. Results We identified a cKD biosignature (n = 39; HC, n = 16) that was validated in two additional cohorts of children with cKD (n = 37; HC, n = 20) and inKD (n = 13; HC, n = 8) and was characterized by overexpression of inflammation, platelets, apoptosis and neutrophil genes, and underexpression of T and NK cell genes. Classifier genes discriminated KD from adenovirus with higher sensitivity and specificity (92% and 100%, respectively) than for GAS (75% and 87%, respectively). We identified a genomic score (MDTH) that was higher at baseline in IVIG-NR [median 12,290 vs. 5,572 in responders, p = 0.009] and independently predicted IVIG-NR. Conclusion A reproducible biosignature from KD patients was identified, and was similar in children with cKD and inKD. A genomic score allowed early identification of children at higher risk for non-response to IVIG. PMID:29813106

Transforming Growth Factor-β Signaling Pathway in Patients with Kawasaki Disease

PubMed Central

Shimizu, Chisato; Jain, Sonia; Lin, Kevin O.; Molkara, Delaram; Frazer, Jeffrey R.; Sun, Shelly; Baker, Annette L.; Newburger, Jane W.; Rowley, Anne H.; Shulman, Stanford T.; Davila, Sonia; Hibberd, Martin L.; Burgner, David; Breunis, Willemijn B.; Kuijpers, Taco W.; Wright, Victoria J.; Levin, Michael; Eleftherohorinou, Hariklia; Coin, Lachlan; Popper, Stephen J.; Relman, David A.; Fury, Wen; Lin, Calvin; Mellis, Scott; Tremoulet, Adriana H.; Burns, Jane C.

2011-01-01

Background Transforming growth factor (TGF)-β is a multifunctional peptide that is important in T-cell activation and cardiovascular remodeling, both of which are important features of Kawasaki disease (KD). We postulated that variation in TGF-β signaling might be important in KD susceptibility and disease outcome. Methods and Results We investigated genetic variation in 15 genes belonging to the TGF-β pathway in a total 771 KD subjects of mainly European descendent from the US, UK, Australia and the Netherlands. We analyzed transcript abundance patterns using microarray and RT-PCR for these same genes and measured TGF-β2 protein levels in plasma. Genetic variants in TGFB2, TGFBR2 and SMAD3 and their haplotypes were consistently and reproducibly associated with KD susceptibility, coronary artery aneurysm formation, aortic root dilatation, and intravenous immunoglobulin treatment response in different cohorts. A SMAD3 haplotype associated with KD susceptibility replicated in two independent cohorts and an intronic SNP in a separate haplotype block was also strongly associated (A/G, rs4776338) (p=0.000022, OR 1.50, 95% CI 1.25-1.81). Pathway analysis using all 15 genes further confirmed the importance of the TGF-β pathway in KD pathogenesis. Whole blood transcript abundance for these genes and TGF-β2 plasma protein levels changed dynamically over the course of the illness. Conclusions These studies suggest that genetic variation in the TGF-β pathway influences KD susceptibility, disease outcome, and response to therapy and that aortic root and coronary artery Z scores can be used for phenotype/genotype analyses. Analysis of transcript abundance and protein levels further support the importance of this pathway in KD pathogenesis. PMID:21127203

Genetic variants of CD209 associated with Kawasaki disease susceptibility.

PubMed

Kuo, Ho-Chang; Huang, Ying-Hsien; Chien, Shu-Chen; Yu, Hong-Ren; Hsieh, Kai-Sheng; Hsu, Yu-Wen; Chang, Wei-Chiao

2014-01-01

Kawasaki disease (KD) is a systemic vasculitis with unknown etiology mainly affecting children in Asian countries. Dendritic cell-specific intercellular adhesion molecule-3 grabbing non-integrin (DC-SIGN, CD209) in humans was showed to trigger an anti-inflammatory cascade and associated with KD susceptibility. This study was conducted to investigate the association between genetic polymorphisms of CD209 and the risk KD. A total of 948 subjects (381 KD and 567 controls) were recruited. Nine tagging SNPs (rs8112310, rs4804800, rs11465421, rs1544766, rs4804801, rs2287886, rs735239, rs735240, rs4804804) were selected for TaqMan allelic discrimination assay. Clinical phenotypes, coronary artery lesions (CAL) and intravenous immunoglobulin (IVIG) treatment outcomes were collected for analysis. Significant associations were found between CD209 polymorphisms (rs4804800, rs2287886, rs735240) and the risk of KD. Haplotype analysis for CD209 polymorphisms showed that A/A/G haplotype (P = 0.0002, OR = 1.61) and G/A/G haplotype (P = 0.0365, OR = 1.52) had higher risk of KD as compared with G/G/A haplotype in rs2287886/rs735239/rs735240 pairwise allele analysis. There were no significant association in KD with regards to CAL formation and IVIG treatment responses. CD209 polymorphisms were responsible for the susceptibility of KD, but not CAL formation and IVIG treatment responsiveness.

Soy isoflavone intake is associated with risk of Kawasaki disease

PubMed Central

Portman, Michael A.; Navarro, Sandi L.; Bruce, Margaret E.; Lampe, Johanna W.

2016-01-01

Kawasaki disease (KD) is an acute vasculitis affecting children. Incidence of KD varies according to ethnicity and is highest in Asian populations. Although genetic differences may explain this variation, dietary or environmental factors could also be responsible. The objectives of this study were to determine dietary soy and isoflavone consumption in a cohort of KD children just before disease onset and their mothers' intake during pregnancy and nursing. We tested the hypothesis that soy isoflavone consumption is associated with risk of KD in US children, potentially explaining some of the ethnic-cultural variation in incidence. We evaluated soy food intake and isoflavone consumption in nearly 200 US KD cases and 200 age-matched controls using a food frequency questionnaire for children and in their mothers. We used a logistic regression model to test the association of isoflavones and KD. Maternal surveys on soy intake during pregnancy and nursing showed no significant differences in isoflavone consumption between groups. However, we identified significantly increased KD risk in children for total isoflavone (odds ratio [OR], 2.33; 95%confidence interval [CI], 1.37–3.96) and genistein (OR, 2.46; 95% CI, 1.46–4.16) intakes, when comparing high soy consumers vs nonconsumers. In addition, significantly increased KD risk occurred in Asian-American children with the highest consumption (total isoflavones: OR, 7.29; 95% CI, 1.73–30.75; genistein: OR, 8.33; 95% CI, 1.92–36.24) compared to whites. These findings indicate that childhood dietary isoflavone consumption, but not maternal isoflavone intake during pregnancy and nursing, relates to KD risk in an ethnically diverse US population. PMID:27440537

Infliximab for the Treatment of Refractory Kawasaki Disease: A Nationwide Survey in Japan.

PubMed

Masuda, Hiroshi; Kobayashi, Tohru; Hachiya, Akira; Nakashima, Yasutaka; Shimizu, Hiroyuki; Nozawa, Tomo; Ogihara, Yoshihito; Ito, Shuichi; Takatsuki, Shinichi; Katsumata, Nobuyuki; Suzuki, Yasuo; Takenaka, Satoshi; Hirono, Keiichi; Kobayashi, Tomio; Suzuki, Hiroshi; Suganuma, Eisuke; Takahashi, Kei; Saji, Tsutomu

2018-04-01

To assess the safety and efficacy of infliximab (IFX) for the treatment of patients with Kawasaki disease (KD). This was a nationwide survey of 274 Japanese institutions exploring how IFX was used to treat patients with KD. The patients' sex, age, treatment course, pre- and post-IFX therapy blood test results, coronary artery lesions (CALs), and adverse events (AEs) were evaluated. We analyzed 434 patients with KD who received IFX between March 2005 and November 2014. The median age at onset was 33 months (range 1-138), and 66 patients (15.2%) were under 1 year old. In all cases, IFX was administered as additional treatment. The median days of illness at the initiation of IFX was 9 days. In 275 patients (63.4%), IFX was administered as third-line treatment, and in 106 patients (24.4%), IFX was administered as fourth-line treatment. Single dose IFX 5 mg/kg was administered to 412 patients (94.9%). After IFX, 363 patients (83.6%) became afebrile within 2 days, and the white blood cell count, percentage of neutrophils, and serum C-reactive protein levels significantly decreased (P < .001), although 119 patients (27.4%) received additional treatment. Before IFX, 132 patients (30.4%) had already developed CALs. In patients without CALs before IFX, 31 patients (10.3%) newly developed CAL after IFX, whereas 32 patients (24.2%) with CAL before IFX showed increased CAL severity. Eighty AEs were observed in 69 patients (15.9%); however, serious AEs were few and reversible. IFX might be an effective and tolerable treatment for refractory KD. Copyright © 2017 Elsevier Inc. All rights reserved.

Laboratory Biomarkers to Facilitate Differential Diagnosis between Measles and Kawasaki Disease in a Pediatric Emergency Room: A Retrospective Study.

PubMed

Buonsenso, Danilo; Macchiarulo, Giulia; Supino, Maria Chiara; La Penna, Francesco; Scateni, Simona; Marchesi, Alessandra; Reale, Antonino; Boccuzzi, Elena

2018-01-01

This retrospective study was conducted to analyze clinical and laboratoristic parameters to individuate specific differences and facilitate differential diagnosis between Measles and Kawasaki Disease (KD) at first evaluation in an emergency room. We found similar clinical features as duration of fever and number of KD criteria (p > 0.5) but significant differences in white blood cell count, neutrophils, CRP and LDH levels (p < 0.001). LDH value ≥ 800 mg/dl had sensibility of 89% and specificity of 90% for Measles while CRP ≥ 3 mg/dl had sensibility 89% and specificity of 85% for KD. The combined use of CRP, LDH and AST showed accuracy of 86.67%.

ST-elevation myocardial infarction in a young adult secondary to giant coronary aneurysm thrombosis: an important sequela of Kawasaki disease and a management challenge.

PubMed

Potter, Elizabeth L; Meredith, Ian T; Psaltis, Peter James

2016-01-20

Thrombosis of a coronary artery aneurysm (CAA) is a rare trigger for ST-elevation myocardial infarction (STEMI) and an important cause of STEMI in young adults previously affected by Kawasaki disease. Initial management should proceed in line with standard STEMI-management guidelines advocating antiplatelet medication and emergency coronary angiography. Acute CAA thrombosis presents the interventional cardiologist with unique challenges during attempted percutaneous revascularisation. In the absence of consensus guidelines, experiential reporting can therefore be of great value. We report on a 36-year-old Vietnamese woman presenting with an inferior STEMI secondary to two giant thrombosed aneurysms of the right coronary artery. Coronary wiring and thrombus aspiration temporarily improved coronary flow but recurrent thrombus with distal embolisation resulted in ventricular fibrillation and cardiogenic shock. Emergency surgical revascularisation subsequently provided a definitive and successful outcome. We discuss the challenges of percutaneous coronary intervention in this scenario and review previous reports to give an overview of principles of decision-making and management. 2016 BMJ Publishing Group Ltd.

Atrioventricular depolarization differences identify coronary artery anomalies in Kawasaki disease.

PubMed

Cortez, Daniel; Sharma, Nandita; Jone, Pei-Ni

2017-03-01

Kawasaki disease (KD) is the leading cause of acquired heart disease in children. Signal average electrocardiogram changes in patients during the acute phase of KD with coronary artery anomalies (CAA) include depolarization changes. We set out to determine if 12-lead-derived atrioventricular depolarization differences can identify CAA in patients with KD. A blinded, retrospective case-control study of patients with KD was performed. Deep Q waves, corrected QT-intervals (QTc), spatial QRS-T angles, T-wave vector magnitudes (RMS-T), and a novel parameter for assessment of atrioventricular depolarization difference (the spatial PR angle) and a two dimensional PR angle were assessed. Comparisons between groups were performed to test for significant differences. One hundred one patients with KD were evaluated, with 68 having CAA (67.3%, mean age 3.6 ± 3.0 years, 82.6% male), and 32 without CAA (31.7%, mean age 2.7 ± 3.2 years, 70.4% male). The spatial PR angle significantly discriminated KD patients with CAA from those without, 59.7° ± 31.1° versus 41.6° ± 11.5° (p < .001). A spatial PR angle cutoff value of 56.9° gave positive/negative predictive values and odds ratios of 93.8%, 43.5%, and 11.5% (95% confidence interval (CI) 2.6-52.2). The two dimensional PR angle either below 7° or above 92° gave positive/negative predictive values and odds ratios of 100.0%, 38.8%, and 21.1% (95% CI 1.2-362.8). No other parameters significantly differentiated the groups. Atrioventricular depolarization differences, measured by the spatial or two dimensional PR angle differentiate KD patients with CAA versus those without. © 2016 Wiley Periodicals, Inc.

Genetic Variants of CD209 Associated with Kawasaki Disease Susceptibility

PubMed Central

Kuo, Ho-Chang; Huang, Ying-Hsien; Chien, Shu-Chen; Yu, Hong-Ren; Hsieh, Kai-Sheng; Hsu, Yu-Wen; Chang, Wei-Chiao

2014-01-01

Background Kawasaki disease (KD) is a systemic vasculitis with unknown etiology mainly affecting children in Asian countries. Dendritic cell-specific intercellular adhesion molecule-3 grabbing non-integrin (DC-SIGN, CD209) in humans was showed to trigger an anti-inflammatory cascade and associated with KD susceptibility. This study was conducted to investigate the association between genetic polymorphisms of CD209 and the risk KD. Methods A total of 948 subjects (381 KD and 567 controls) were recruited. Nine tagging SNPs (rs8112310, rs4804800, rs11465421, rs1544766, rs4804801, rs2287886, rs735239, rs735240, rs4804804) were selected for TaqMan allelic discrimination assay. Clinical phenotypes, coronary artery lesions (CAL) and intravenous immunoglobulin (IVIG) treatment outcomes were collected for analysis. Results Significant associations were found between CD209 polymorphisms (rs4804800, rs2287886, rs735240) and the risk of KD. Haplotype analysis for CD209 polymorphisms showed that A/A/G haplotype (P = 0.0002, OR = 1.61) and G/A/G haplotype (P = 0.0365, OR = 1.52) had higher risk of KD as compared with G/G/A haplotype in rs2287886/rs735239/rs735240 pairwise allele analysis. There were no significant association in KD with regards to CAL formation and IVIG treatment responses. Conclusion CD209 polymorphisms were responsible for the susceptibility of KD, but not CAL formation and IVIG treatment responsiveness. PMID:25148534

Ambient air pollution, temperature and kawasaki disease in Shanghai, China.

PubMed

Lin, Zhijing; Meng, Xia; Chen, Renjie; Huang, Guoying; Ma, Xiaojing; Chen, Jingjing; Huang, Min; Huang, Meirong; Gui, Yonghao; Chu, Chen; Liu, Fang; Kan, Haidong

2017-11-01

Kawasaki disease (KD) is a kind of pediatric vasculitis of unknown etiology which mainly affects the development of coronary artery aneurysms. Few studies have explored the potential environmental risk factors on KD incidence. We performed a time-series analysis to investigate the associations between air pollution and temperature and KD in Shanghai, China. We collected daily-hospitalized KD patients that were admitted in major pediatric specialty hospitals located in the urban areas of Shanghai from 2001 to 2010. The over-dispersed generalized additive model was used to estimate the effects of air pollutants on KD incidence on each day. Then, this model was combined with a distributed lag non-linear model to estimate the cumulative effects of temperature over a week. There were positive but statistically insignificant associations between three major air pollutants and KD incidence. The association between daily mean temperature and KD was generally J-shaped with higher risks on hot days. The cumulative relative risk of KD at extreme hot temperature (99th percentile, 32.4 °C) over a week was 1.91 [95% confidence interval (CI): 1.13, 3.23], compared with the referent temperature (10.0 °C). This study suggested that a short-term exposure to high temperature may significantly increase the incidence of KD, and the evidence linking air pollution and KD incidence was limited. Copyright © 2017 Elsevier Ltd. All rights reserved.

Ethnic Kawasaki Disease Risk Associated with Blood Mercury and Cadmium in U.S. Children

PubMed Central

Yeter, Deniz; Portman, Michael A.; Aschner, Michael; Farina, Marcelo; Chan, Wen-Ching; Hsieh, Kai-Sheng; Kuo, Ho-Chang

2016-01-01

Kawasaki disease (KD) primarily affects children <5 years of age (75%–80%) and is currently the leading cause of acquired heart disease in developed nations. Even when residing in the West, East Asian children are 10 to 20 times more likely to develop KD. We hypothesized cultural variations influencing pediatric mercury (Hg) exposure from seafood consumption may mediate ethnic KD risk among children in the United States. Hospitalization rates of KD in US children aged 0–4 years (n = 10,880) and blood Hg levels in US children aged 1–5 years (n = 713) were determined using separate US federal datasets. Our cohort primarily presented with blood Hg levels <0.1 micrograms (µg) per kg bodyweight (96.5%) that are considered normal and subtoxic. Increased ethnic KD risk was significantly associated with both increasing levels and detection rates of blood Hg or cadmium (Cd) in a linear dose-responsive manner between ethnic African, Asian, Caucasian, and Hispanic children in the US (p ≤ 0.05). Increasing low-dose exposure to Hg or Cd may induce KD or contribute to its later development in susceptible children. However, our preliminary results require further replication in other ethnic populations, in addition to more in-depth examination of metal exposure and toxicokinetics. PMID:26742052

Thrombospondin-2 predicts response to treatment with intravenous immunoglobulin in children with Kawasaki disease.

PubMed

Yang, Shuai; Song, Ruixia; Li, Xiaohui; Zhang, Ting; Fu, Jin; Cui, Xiaodai

2018-01-01

To investigate the predictive value of thrombospondin-2 (TSP-2) in assessing the response to intravenous immunoglobulin (IVIG) in children with acute Kawasaki disease (KD). This was a cohort study with controls. 71 children with KD were recruited as the case group, including IVIG non-responder (n=17) and IVIG responder (n=54), and healthy children (n=27) and febrile children (n=30) were used as control groups. ELISA was used to measure plasma TSP-2 and TSP-1 levels. The rank-sum test was used to compare groups of non-normally distributed data. Predictive value was evaluated through the receiver operating characteristic (ROC) curve. Compared with the control groups, the plasma TSP-2 levels in acute KD were significantly elevated (TSP-2: 31.00 (24.02, 39.28) vs 21.93 (17.00, 24.73) vs 16.23 (14.00, 19.64) ng/mL, P<0.001). The plasma TSP-2 level in the IVIG non-responder was significantly higher than the responder group (37.58 (31.86, 43.98) vs 27.84 (21.88, 33.48) ng/mL, P=0.002). When using an ROC curve to analyse the predictive effect of TSP-2 on non-responsiveness to IVIG treatment, the area under the curve was 0.752 (0.630, 0.875) (P=0.002). When the cut-off value for TSP-2 was 31.50 ng/mL, the sensitivity was 82.35%, the specificity was 64.81%. The plasma TSP-2 level was elevated in acute KD and it might be a novel predictor for IVIG resistance, which could help guide clinicians to choose individualised initial therapeutic regimens.

The biophysical properties of the aorta are altered following Kawasaki disease.

PubMed

Vaujois, Laurence; Dallaire, Frédéric; Maurice, Roch L; Fournier, Anne; Houde, Christine; Thérien, Johanne; Cartwright, Daniel; Dahdah, Nagib

2013-12-01

The long-term sequelae of Kawasaki disease (KD) are based on the coronary complications. Because KD causes generalized vasculitis, with documented aneurysms in the femoral, iliac, renal, axillary, and brachial arteries, the aim of this study was to assess the biophysical properties of the aorta (BPA) after KD. The BPA are biometric measurements representing vascular structural and dynamic changes in response to cardiac work. Anthropometric and echocardiographic measurements of the aorta in a series of patients with KD were compared with those of healthy subjects. The BPA were calculated noninvasively by extrapolating previously validated equations that were conceived for invasive measurements. Because BPA vary with body habitus, control subjects were used to normalize BPA parameters for height to compute BPA Z-score equations. Between June 2007 and February 2010, BPA were recorded in 57 patients with KD >1 year after the onset of the disease, 45 without and 12 with coronary artery sequelae. The mean intervals between the acute onset of KD and enrollment were 10.0 ± 5.0 and 5.8 ± 4.5 years for patients with and without coronary artery sequelae, respectively (P = .008). Patients with KD with coronary artery sequelae had significantly altered Z scores of aortic diameter modulation, Peterson's elastic modulus, and β stiffness index (P = .001-.016). Patients with KD without coronary artery sequelae also exhibited altered elasticity, stiffness, and pulse-wave velocity (P = .001-.026). Altered BPA after KD are detectible despite apparent resolution of acute vasculitis. Future directions toward determining multilevel and multilayer vascular impact, including vascular autonomous homeostasis, require thorough investigation. Copyright © 2013 American Society of Echocardiography. Published by Mosby, Inc. All rights reserved.

Kawasaki Disease

MedlinePlus

... descent. The disease is more likely to affect boys than girls. Most cases occur in children younger than 5 ... descent. The disease is more likely to affect boys than girls. Most cases occur in children younger than 5 ...

Atypical desquamation in a 2.5-year-old boy with Kawasaki disease: A case report.

PubMed

Adib, Ali; Fazel, Ali; Nabavizadeh, Seyed Hesamedin; Alyasin, Sohaila; Kashef, Sara

2017-02-01

Kawasaki disease (KD) is a vasculitis that mostly affects children under 5 years of age. This article presents a 2.5-year-old boy who presented with 6 days of fever, generalized maculopapular rash, bilateral non-exudative conjunctivitis, cracked lips, right cervical lymphadenopathy, erythematous extremities, and perianal desquamation. Laboratory studies showed leukocytosis and sterile pyuria. Because diagnosis of KD was proved, oral acetylsalicylic acid with the anti-inflammatory dose and intravenous immunoglobulin were started for him. On the seventh day of admission time, he developed desquamation and erythema on the site of his right cervical lymphadenopathy as well as periungual scaling. About three weeks after starting the treatment, scaling of the cervical lymphadenopathy and periungual area stopped. Echocardiography was performed for him three times: at the time of diagnosis, four weeks, and 6 months later and revealed normal coronary arteries. We report this sign, desquamation on the site of cervical lymphadenopathy, as a new finding.

Kawasaki Disease

MedlinePlus

... is to relieve symptoms and prevent long-term damage. Most children who have the rare disease require a hospital ... stay home from school or day care. Some children may need ongoing treatment. This is necessary if they suffer damage or are at risk of health disease. Questions ...

Acute kidney injury and cholestasis associated with Kawasaki disease in a 9-year-old: Case report.

PubMed

Martínez Vázquez, José Allan; Sánchez García, Carlos; Rodríguez Muñoz, Lorena; Martínez Ramírez, Rogelio Osvaldo

2017-12-15

Kawasaki disease (KD) is a systemic vasculitis frequent in children younger than 5 years of age. It involves coronary arteries and other medium-sized vessels. There also exists evidence of inflammatory and proliferative changes affecting the biliary tract and lymphocyte infiltration of the renal interstitial. We describe the case of a 9-year-old girl who developed high-grade fever, bilateral non-purulent conjunctivitis, «strawberry» tongue, desquamation of the fingers and toes, cholestatic syndrome, edema and elevated serum creatinine. KD is a diagnostic challenge for the pediatrician. In every patient with high-grade fever, cholestasis and acute kidney injury, KD should be included in the differential diagnosis, even though more research is necessary to evaluate this atypical association. Copyright © 2017 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

Cardiac Complications in 38 Cases of Kawasaki Disease with Coronary Artery Aneurysm Diagnosed by Echocardiography.

PubMed

Wei, Ya Juan; Zhao, Xiao Lan; Liu, Bao Min; Niu, Hua; Li, Qian

2016-05-01

The long-term prognosis of patients with Kawasaki disease (KD) complicated by coronary artery aneurysm (CAA) is unclear. The aim of this study was to evaluate the complications of KD with CAAs. We retrospectively analyzed the clinical data and complications of 38 KD patients with CAAs who were treated and underwent regular follow-up with echocardiography between January 1989 and May 2013. During a period of 29 days to 19 years after disease onset, complications seen included coronary stenosis and occlusion (six patients), thrombosis (17 patients), myocardial infarction (six patients), and calcification of CAAs (seven patients). Rupture of giant CAAs occurred in two patients and caused sudden death in one of these patients at 29 days and in the other patient at 5 months after disease onset. A total of seven deaths occurred, with five deaths caused by myocardial infarction. Three of these had undiagnosed incomplete KD or had not received regular treatment, while two experienced sudden death after several asymptomatic myocardial infarctions. Cardiac complications of KD with CAAs include thrombosis, coronary stenosis, myocardial infarction, sudden death, and calcification. Although rare, rupture of giant CAAs is fatal and might occur earlier after the onset of disease. Mortality occurred primarily in the earlier cases when anticoagulant therapy was insufficient and in patients who did not receive regular treatment. Echocardiography can provide reliable information for assessing the progression and prognosis of this condition. © 2015, Wiley Periodicals, Inc.

Lack of association between miR-218 rs11134527 A>G and Kawasaki disease susceptibility.

PubMed

Pi, Lei; Fu, Lanyan; Xu, Yufen; Che, Di; Deng, Qiulian; Huang, Xijing; Li, Meiai; Zhang, Li; Huang, Ping; Gu, Xiaoqiong

2018-05-01

Abstract Kawasaki disease (KD) is a type of disease that includes the development of a fever that lasts at least five days and involves the clinical manifestation of multicellular vasculitis. KD has become one of the most common pediatric cardiovascular diseases. Previous studies have reported that miR-218 rs11134527 A>G is associated with susceptibility to various cancer risks. However, there is a lack of evidence regarding the relationship between this polymorphism and KD risk. This study explored the correlation between the miR-218 rs11134527 A>G polymorphism and the risk of KD. We recruited 532 patients with KD and 623 controls to genotype the miR-218 rs11134527 A>G polymorphism with a TaqMan allelic discrimination assay. Our results illustrated that the miR-218 rs11134527 A>G polymorphism was not associated with KD risk. In an analysis stratified by age, sex, and coronary artery lesions, we found only that the risk of KD was significantly decreased for children older than 5 years (GG vs. AA/AG: adjusted OR=0.26, 95% CI=0.07-0.94, P =0.041). This study demonstrated that the miR-218 rs1113452 A>G polymorphism may have an age-related relationship with KD susceptibility that has not previously been revealed. ©2018 The Author(s).

Giant aneurysms: A gender-specific complication of Kawasaki disease?

PubMed

Dietz, Sanne M; Kuipers, Irene M; Tacke, Carline E A; Koole, Jeffrey C D; Hutten, Barbara A; Kuijpers, Taco W

2017-10-01

Kawasaki disease (KD) is a pediatric vasculitis of unknown origin. Its main complication is the development of coronary artery aneurysms (CAA) with giant CAA at the end of the spectrum. In this cohort study, we evaluated the association between patient characteristics and the development of giant CAA based on z-scores. Multivariable, multinomial logistic regression analysis was used to identify variables associated with giant CAA. A total of 301 KD patients, comprising 216 patients without enlargement, 45 with small-sized, 19 with medium-sized, and 21 with giant CAA with all echocardiographies at our center were retrospectively included. Remarkably, 95% of patients with giant CAA were boys. In addition to 'no/late intravenous immunoglobulin (IVIG) treatment', 'male gender' (OR 16.23, 95% CI 1.88-140.13), 'age<1 year' (OR 7.49, 95% CI 2.29-24.46), and 'IVIG re-treatment (9.79, 95% CI 2.79-34.37)' were significantly associated with an increased risk of giant CAA, with patients without enlargement as reference. Compared to patients with medium-sized CAA, 'IVIG re-treatment' was significantly associated with giant CAA. The majority of giant CAA continued to increase in size during the first 40 days. We identified risk factors associated with an increased risk of giant CAA. The difference in variables between the giant CAA group and the other CAA subgroups suggests a separation between patients with the treatment-resistant giant CAA and the other IVIG-responsive patients, in which gender may be factored as a most relevant genetic trait. The increase in size during the first 2 months indicates the need for repeated echocardiography. Copyright © 2017 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

Evaluation of echogenicity of the heart in Kawasaki disease.

PubMed

Nagata, Hazumu; Yamamura, Kenichiro; Uike, Kiyoshi; Nakashima, Yasutaka; Hirata, Yuichiro; Morihana, Eiji; Mizuno, Yumi; Ishikawa, Shiro; Hara, Toshiro

2014-08-01

Pathologic studies of the heart in patients with Kawasaki disease (KD) revealed vasculitis, valvulitis, myocarditis, and pericarditis. However, there have been no studies on the quantitative determination of multi-site echogenicity of the heart in KD patients. It is also undetermined whether the degree of echogenicity of each site of the heart in patients with KD might be related to the response to intravenous immunoglobulin (IVIG) treatment. In 81 KD patients and 30 control subjects, we prospectively analyzed echogenicity of the heart. Echogenicity was measured in four sites: coronary artery wall (CAW), mitral valve (MV), papillary muscle (PM), and ascending aortic wall (AAo wall) by the calibrated integrated backscatters (cIBs). The cIB values of all measurement sites at acute phase in KD patients were significantly higher than those in control subjects (KD patients vs control subjects; CAW, 19.8 ± 6.2 dB vs 14.5 ± 2.0 dB, p < 0.05; MV, 23.3 ± 5.3 dB vs 16.0 ± 3.3 dB, p < 0.05; PM, 22.4 ± 5.1 dB vs 12.7 ± 1.9 dB, p < 0.05; AAo wall, 25.3 ± 5.6 dB vs 18.3 ± 3.4 dB, p < 0.05). The cIB values of CAW at the acute phase in IVIG nonresponders were significantly higher than those in responders. Conclusion: Echogenicity of the heart in KD patients at the acute phase increased not only in the coronary artery wall but also in other parts of the heart. Echogenicity of CAW might be helpful in determining the unresponsiveness of IVIG treatment.

Use of Lagrangian transport models and Sterilized High Volume Sampling to pinpoint the source region of Kawasaki disease and determine the etiologic agent

NASA Astrophysics Data System (ADS)

Curcoll Masanes, Roger; Rodó, Xavier; Anton, Jordi; Ballester, Joan; Jornet, Albert; Nofuentes, Manel; Sanchez-Manubens, Judith; Morguí, Josep-Anton

2015-04-01

Kawasaki disease (KD) is an acute, coronary artery vasculitis of young children, and still a medical mystery after more than 40 years. A former study [Rodó et al. 2011] demonstrated that certain patterns of winds in the troposphere above the earth's surface flowing from Asia were associated with the times of the annual peak in KD cases and with days having anomalously high numbers of KD patients. In a later study [Rodó et al. 2014], we used residence times from an Air Transport Model to pinpoint the source region for KD. Simulations were generated from locations spanning Japan from days with either high or low KD incidence. In order to cope with stationarity of synoptic situations, only trajectories for the winter months, when there is the maximum in KD cases, were considered. Trajectories traced back in time 10 days for each dataset and location were generated using the flexible particle Lagrangian dispersion model (FLEXPART Version 8.23 [Stohl et al. 2005]) run in backward mode. The particles modeled were air tracers, with 10,000 particles used on each model run. The model output used was residence time, with an output grid of 0.5° latitude × longitude and a time resolution of 3 h. The data input used for the FLEXPART model was gridded atmospheric wind velocity from the European Center for Medium-Range Weather Forecasts Re-Analysis (ERA-Interim at 1°). Aggregates of winter period back-trajectories were calculated for three different regions of Japan. A common source of wind air masses was located for periods with High Kawasaki disease. Knowing the trajectories of winds from the air transport models, a sampling methodology was developed in order to capture the possible etiological agent or other tracers that could have been released together. This methodology is based on the sterilized filtering of high volumes of the transported air at medium tropospheric levels by aircraft sampling and a later analyze these filters with adequate techniques. High purity

Fluctuations of the Concentration of Cs-137 Aerosol in Chernobyl,Fukushima and Kawasaki

NASA Astrophysics Data System (ADS)

Ota, Yohei; Hatano, Yuko; Okada, Yukiko; Hirose, Katsumi

2017-04-01

Statistical analysis is applied to a time series of the airborne concentration of Cs-137. In order to extract fractal characteristics of the fluctuations, we employed the Hurst analysis. Interestingly, the Hurst index is around 1/3, which is common to the Chernobyl data, Fukushima data, and Kawasaki data. The Kawasaki data is measured by the Tokyo City University, located at 40km south to Tokyo. We proposed a stochastic differential equation, based on an advection equation with winds fluctuating probabilistically. The averaged solution of the equation is compared with measured data. We found that the index of the power of the time is -4/3, which is common to the three cases, Chernobyl, Fukushima and Kawasaki.

[Kawasaki disease is more prevalent in rural areas of Catalonia (Spain)].

PubMed

Sánchez-Manubens, Judith; Antón, Jordi; Bou, Rosa; Iglesias, Estibaliz; Calzada-Hernandez, Joan; Rodó, Xavier; Morguí, Josep-Antón

2017-10-01

Kawasaki disease (KD) is an acute self-limited systemic vasculitis relatively common in childhood. The etiology of KD is still unknown, although clinical, laboratory and epidemiological features suggest an infectious origin or trigger. Differences on incidence between countries have been related to specific genetic factors, ethnicity, country of birth and some other sociocultural and environmental factors. We present a population-based study on incidence of KD in Catalonia (Spain), focusing on differences between patients in rural and non-rural areas of the region. Observational population-based study including all Pediatric Units in Catalan hospitals, between 2004 and 2014. A 12-month (March 2013-March 2014) prospective collection of new cases of KD was carried out to determine the incidence of KD. The rest of the data was retrieved retrospectively. Data from 399 patients over the 10-year study period was analyzed. Among the total KD patients, 353 (88.5%) lived in non-rural areas and 46 (11.5%) in rural areas. It was found that there is a significant difference (P<.001) between the percentage of rural population observed in patients with KD (11.5%), and the expected 5% of the Catalan population. This is the first population-based study showing significant differences on KD incidence rates between rural and non-rural areas. Copyright © 2016 Asociación Española de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.

Incidence, epidemiology and clinical features of Kawasaki disease in Catalonia, Spain.

PubMed

Sánchez-Manubens, Judith; Antón, Jordi; Bou, Rosa; Iglesias, Estíbaliz; Calzada-Hernandez, Joan

2016-01-01

To assess the incidence, epidemiology and clinical features of Kawasaki disease (KD) in Catalonia (northeast region of Spain). This was an observational population-based study including all Paediatric Units in Catalonia, under both public and private management. Retrospective data retrieval was performed for 10 years (2004-2013). A 12-month (March 2013 to March 2014) prospective collection of new cases of KD was carried out to determine the incidence of KD. Data from 399 patients over the 10-year study period was analysed, revealing that 233 (58.4%) had complete KD, 159 (39.8) incomplete KD and 7 (1.7%) were considered atypical KD. Mean annual incidence was 3.5/105 children <14 years old (yo) and 8/105 children <5 yo (mean age 37±33 months, range 1.3-191.3). KD was more frequent in boys (59.6%, p<0.001) and in rural areas (p<0.001). Patients with IVIG non-responsiveness, need of a 2(nd) IVIG dose, delay of treatment >10(th) day of illness, ages <1 yo and >8 yo and the presence of sterile piuria, aseptic meningitis, abdominal pain and uveitis at diagnosis were found to have higher risk of coronary aneurisms (CAA) (p<0.05). This is the first population-based study on the epidemiology of KD in the western Mediterranean area. Incidence, clinical features and treatment plans in our cohort are similar to those described in other European studies.

Kawasaki disease: a rare pediatric pathology in Mexico. Twenty cases report from the Hospital Infantil del Estado de Sonora.

PubMed

Sotelo, Norberto; González, Luis Antonio

2007-01-01

Kawasaki disease (KD) is an etiological illness that is relatively unknown and scarcely identified in Mexico; it affects children mainly aged 1-4 years, evolves with fever, vasculitis in diverse organs, and in the heart the disease mainly affects the coronary arteries. Our aim was to inform the clinical findings and evolution of 20 patients diagnosed with KD. We reviewed the patient clinical files retrospectively and descriptively to obtain information with regard to age, sex, clinical signs, laboratory and consultory results, echocardiography findings, complications, evolution during hospitalization, followup, and out-patient ambulatory consultations. Eighteen patients were male, two were female, six developed coronary damage, two aortic mitral-valve insufficiency, one pericardial shedding, and one, myocarditis. All patients received gamma globulin treatment with aspirin, and 16 were controlled during 6-8 months after the acute medical profile. The opportune clinical diagnostic it is fundamental to establish an early treatment with gammmaglobuline to avoid injuries in the arterial coronary level. This injury may cause eventualy ischemia or myocardial infarct

Hounsfield unit values of retropharyngeal abscess-like lesions seen in Kawasaki disease.

PubMed

Sasaki, Toru; Miyata, Rie; Hatai, Yoshiho; Makita, Kohzoh; Tsunoda, Koichi

2014-04-01

Retropharyngeal abscess-like lesions are occasionally seen in computed tomography (CT) imaging of patients with Kawasaki disease (KD) and these patients often undergo unnecessary surgery. We could distinguish the lesions from true abscesses by measuring their Hounsfield unit values (HUs). To distinguish the retropharyngeal abscess-like lesions from true abscesses without any surgical procedure. We investigated six cases of KD showing such lesions on CTs, both with and without contrast enhancement (CE). We measured the HUs of those lesions and compared them with those of 10 true abscesses as controls. Abscess-like lesions of KD were well enhanced by CE, whereas abscesses showed virtually no enhancement. The mean HU in the six KD cases was 20.0 ± 4.65 (mean ± SD) on plain CTs and 35.6 ± 4.49 on contrast CTs. In abscesses, it was 30.3 ± 4.42 on plain CTs and 30.3 ± 3.57 on contrast CTs. The difference in HU values [(HU on contrast CT) - (HU on plain CT)] was defined as ΔHU. The mean ΔHU was 15.6 ± 5.36 in the six KD lesions and 0.0 ± 2.93 in abscesses, with statistical significance of p < 0.0001 by Student's t test. Thus, ΔHU value may potentially be a useful parameter for their distinction.

Proteomic analysis associated with coronary artery dilatation caused by Kawasaki disease using serum exosomes.

PubMed

Zhang, Li; Wang, Wei; Bai, Jun; Xu, Yu-Fen; Li, Lai-Qing; Hua, Liang; Deng, Li; Jia, Hong-Ling

2016-05-01

The aim of this study was to investigate the serum exosome proteome profile of coronary artery dilatation (CAD) caused by Kawasaki disease (KD). Two-dimensional electrophoresis was implemented on proteins of serum exosomes obtained from children with CAD caused by KD and from healthy controls. Differentially expressed proteins were identified by matrix-assisted laser desorption/ionization time-of-flight/time-of-flight mass spectrometry analysis. We identified 38 differentially expressed proteins (13 up-regulated and 25 down-regulated) from serum exosomes of patients with CAD caused by KD compared with healthy controls. Expression levels of three differentially expressed proteins (leucine-rich alpha-2-glycoprotein, sex hormone-binding globulin, and serotransferrin) were validated using western blot analysis. Classification and protein-protein network analysis showed that they are associated with multiple functional groups involved in the acute inflammatory response, defense response, complement activation, humoral immune response, and response to wounding. The majority of the proteins are involved in the inflammation and coagulation cascades. These findings establish a comprehensive proteome profile of CAD caused by KD and increase our knowledge of scientific insight into its mechanisms. Copyright © 2016 Sociedade Portuguesa de Cardiologia. Published by Elsevier España. All rights reserved.

Levels of intra- and extracellular heat shock protein 60 in Kawasaki disease patients treated with intravenous immunoglobulin.

PubMed

Yin Ji, Xu; Kang, Mi-Ran; Choi, Jong-Sung; Jeon, Hak-Soo; Han, Heon-Seok; Kim, Ji-Yoon; Son, Bo-Ra; Lee, Young-Min; Hahn, Youn-Soo

2007-09-01

Immune reactivity to autologous heat shock protein 60 (HSP60) has been reported to be associated with a favorable prognosis in autoimmune diseases. To provide a clue for the possible role of HSP60 in Kawasaki disease (KD), we investigated the levels of intra- and extracellular HSP60 in the course of KD. In KD patients, autologous HSP60 was abundantly expressed in CD11c(+) cells during the acute phase and subsequently decreased during the subacute phase. Most of HSP60-expressing CD11c(+) cells observed in the acute phase was composed of CD11c(low) cells instead of CD11c(high) cells, which were dominant in the subacute phase. In contrast, circulating HSP60 levels were higher in the subacute phase than those in the acute phase, reflecting higher level of HSP60 exposure to the immune system of patients during recovery. These changes in the levels of intra- and extracellular HSP60 were not observed in patients with other febrile diseases. The observed features of HSP60 expression in patients with KD are in favor of a role for autologous HSP60 as a regulator for control of inflammation, rather than a proinflammatory mediator in KD.

Epidemiologic Features of Kawasaki Disease in Shanghai From 2008 Through 2012.

PubMed

Chen, Jing-Jing; Ma, Xiao-Jing; Liu, Fang; Yan, Wei-Li; Huang, Mei-Rong; Huang, Min; Huang, Guo-Ying

2016-01-01

This study was to investigate the epidemiologic trends of Kawasaki disease (KD) and coronary arterial lesions (CALs) in Shanghai from 2008 through 2012. Data were collected by using the network of the KD research group established during the first survey in Shanghai to conduct the third survey, covering the period from 2008 through 2012. Clinical records of 2304 patients with acute KD were retrospectively reviewed. Epidemiologic features of KD were investigated. Univariate and multivariate analyses were performed to identify the risk factors for CAL in patients with KD. The data were compared with the previous 2 surveys covering the periods from 1998 to 2002 and 2003 to 2007, respectively. The average incidence of KD was 30.3 to 71.9 per 100,000 children aged 0-4 years from 2008 through 2012. Age at onset ranged from 32 days to 11.7 years (median: 2.3 years). The occurrence of KD was more common in summer and spring. A total of 365 (15.9%) cases developed CAL defined as ectasia or aneurysm. Male, age ≤ 1 year, intravenous immunoglobulin (IVIG) unresponsiveness, a smaller administrative dosage and the delayed administration of IVIG (>10 days) were independent risk factors for CAL. The occurrence of CAL seemed less frequent in patients who received IVIG within 5 days after onset of illness. The incidence of KD in children has increased over time, and the development of CAL decreased in the past 5 years in Shanghai. Earlier treatment with IVIG (<5 days) was associated with reduced CAL among patients with KD.

Renormalized dynamics of the Dean-Kawasaki model

NASA Astrophysics Data System (ADS)

Bidhoodi, Neeta; Das, Shankar P.

2015-07-01

We study the model of a supercooled liquid for which the equation of motion for the coarse-grained density ρ (x ,t ) is the nonlinear diffusion equation originally proposed by Dean and Kawasaki, respectively, for Brownian and Newtonian dynamics of fluid particles. Using a Martin-Siggia-Rose (MSR) field theory we study the renormalization of the dynamics in a self-consistent form in terms of the so-called self-energy matrix Σ . The appropriate model for the renormalized dynamics involves an extended set of field variables {ρ ,θ } , linked through a nonlinear constraint. The latter incorporates, in a nonperturbative manner, the effects of an infinite number of density nonlinearities in the dynamics. We show that the contributing element of Σ which renormalizes the bare diffusion constant D0 to DR is same as that proposed by Kawasaki and Miyazima [Z. Phys. B Condens. Matter 103, 423 (1997), 10.1007/s002570050396]. DR sharply decreases with increasing density. We consider the likelihood of a ergodic-nonergodic (ENE) transition in the model beyond a critical point. The transition is characterized by the long-time limit of the density correlation freezing at a nonzero value. From our analysis we identify an element of Σ which arises from the above-mentioned nonlinear constraint and is key to the viability of the ENE transition. If this self-energy would be zero, then the model supports a sharp ENE transition with DR=0 as predicted by Kawasaki and Miyazima. With the full model having nonzero value for this self-energy, the density autocorrelation function decays to zero in the long-time limit. Hence the ENE transition is not supported in the model.

Usefulness of Age-Stratified N-Terminal Prohormone of Brain Natriuretic Peptide for Diagnosing Kawasaki Disease

PubMed Central

Lee, Sang Hoon; Yoon, Somy; Hong, Seunghee; Yang, Eun Mi; Eom, Gwang Hyeon

2017-01-01

N-terminal prohormone of brain natriuretic peptide (NT-proBNP) was recently reported as a biomarker for diagnosing Kawasaki disease (KD). The basal NT-proBNP level, however, gradually decreases with age. We investigated the usefulness of an age-stratified cutoff value of NT-proBNP for diagnosing KD. All the patients enrolled in this study visited Chonnam National University Hospital between December 2007 and March 2016. The KD groups consisted of 214 patients with complete KD and 129 patients with incomplete KD. The control group included 62 children with simple febrile illness but without heart disease. Laboratory data including NT-proBNP level were evaluated. Each group was divided into subgroups according to patient age (<6 months, 6–12 months, 12–24 months, and >24 months), and different cutoff values of NT-proBNP were calculated. The cutoff values of NT-proBNP used to diagnose total KD and incomplete KD were 762 and 762 pg/mL (<6 months), 310 and 310 pg/mL (6–12 months), 326 and 326 pg/mL (12–24 months), and 208 and 137 pg/mL (>24 months), respectively. In conclusion, age-stratified NT-proBNP is a useful biomarker for the differential diagnosis of KD in patients with a simple febrile illness. PMID:29358841

Pro-inflammatory cytokine single nucleotide polymorphisms in Kawasaki disease.

PubMed

Assari, Raheleh; Aghighi, Yahya; Ziaee, Vahid; Sadr, Maryam; Rahmani, Farzaneh; Rezaei, Arezou; Sadr, Zeinab; Moradinejad, Mohammad Hassan; Raeeskarami, Seyed Reza; Rezaei, Nima

2016-07-25

Kawasaki disease (KD) is a systemic vasculitis of children associated with cardiovascular sequelae. Proinflammatory cytokines play a major role in KD pathogenesis. However, their role is both influenced and modified by regulatory T-cells. IL-1 gene cluster, IL-6 and TNF-α polymorphisms have shown significant associations with some vasculitides. Herein we investigated their role in KD. Fifty-five patients with KD who were randomly selected from referrals to the main pediatric hospital were enrolled in this case-control study. Single nucleotide polymorphisms (SNPs) of the following genes were assessed in patients and 140 healthy subjects as control group: IL-1α at -889 (rs1800587), IL-1β at -511 (rs16944), IL-1β at +3962 (rs1143634), IL-1R at Pst-I 1970 (rs2234650), IL-1RN/A at Mspa-I 11100 (rs315952), TNF-α at -308 (rs1800629), TNF-α at -238, IL-6 at -174 (rs1800795) and IL-6 at +565. Twenty-one percent of the control group had A allele at TNF-α -238 while only 8% of KD patients had A allele at this position (P = 0.003, OR [95%CI] = 0.32 [0.14-0.71]). Consistently, TNF-α genotype GG at -238 had significant association with KD (OR [95% CI] = 4.31 [1.79-10.73]). Most controls carried the CG genotype at IL-6 -174 (n = 93 [66.9%]) while GG genotype was the most common genotype (n = 27 [49%]) among patients. Carriers of the GG haplotype at TNF-α (-308, -238) were significantly more prevalent among the KD group. No association was found between IL-1 gene cluster, allelic or haplotypic variants and KD. TNF-α GG genotype at -238 and GG haplotype at positions -308 and -238 were associated with KD in an Iranian population. © 2016 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.

CFD-based Thrombotic Risk Assessment in Kawasaki Disease Patients with Coronary Artery Aneurysms

NASA Astrophysics Data System (ADS)

Sengupta, Dibyendu; Kung, Ethan; Kahn, Andrew; Burns, Jane; Marsden, Alison

2012-11-01

Coronary aneurysms occur in 25% of untreated Kawasaki Disease (KD) patients and put patients at increased risk for myocardial infarction and sudden death. Clinical guidelines recommend using aneurysm diameter >8 mm as the arbitrary criterion for treating with anti-coagulation therapy. This study uses patient-specific modeling to non-invasively determine hemodynamic parameters and quantify thrombotic risk. Anatomic models were constructed from CT angiographic image data from 5 KD aneurysm patients and one normal control. CFD simulations were performed to obtain hemodynamic data including WSS and particle residence times (PRT). Thrombosis was clinically observed in 4/9 aneurysmal coronaries. Thrombosed vessels required twice as many cardiac cycles (mean 8.2 vs. 4.2) for particles to exit, and had lower mean WSS (1.3 compared to 2.8 dynes/cm2) compared to vessels with non-thrombosed aneurysms of similar max diameter. 1 KD patient in the cohort with acute thrombosis had diameter < 8 mm. Regions of low WSS and high PRT predicted by simulations correlated with regions of subsequent thrombus formation. Thrombotic risk stratification for KD aneurysms may be improved by incorporating both hemodynamic and geometric quantities. Current clinical guidelines to assess patient risk based only on aneurysm diameter may be misleading. Further prospective study is warranted to evaluate the utility of patient-specific modeling in risk stratifying KD patients with coronary aneurysms. NIH R21.

Kawasaki syndrome: a controlled study of an outbreak in Wisconsin.

PubMed

Klein, B S; Rogers, M F; Patrican, L A; White, M C; Burgdorfer, W; Schell, W L; Kochel, R L; Marchette, N J; McPherson, J T; Nelson, D B

1986-08-01

The etiology of Kawasaki syndrome remains unestablished, although a possible role has been suggested for exposure to the application of carpet shampoo, house dust mites, and rickettsial infection. During an outbreak of 20 cases of Kawasaki syndrome that occurred in southeastern Wisconsin from November 1982 through March 1983, a case-control study was done of 15 cases and 30 matched controls. The study included questionnaire administration, dust collection from homes, and serum specimen collection. Only one patient had been exposed to a shampooed carpet within 30 days before onset of illness. No differences were noted between cases and controls in the degree of exposure to house dust mite-associated factors in the home, nor in the occurrence, density and species-specific prevalence of house dust mites in the home. Meadow voles exposed to house dust mites from the homes of patients did not develop serologic or pathologic evidence of infection due to rickettsiae in the spotted fever and typhus groups or Coxiella burnetii. Anti-mite-specific immunoglobulin E was not detected in serum specimens from cases or controls. Results from this study do not support hypotheses suggesting that the development of Kawasaki syndrome is associated with exposure to application of carpet shampoo, house dust mites, or rickettsial infection.

Usefulness of Single Photon Emission Computed Tomography/Computed Tomography Fusion-Hybrid Imaging to Evaluate Coronary Artery Disorders in Patients with a History of Kawasaki Disease.

PubMed

Abe, Masanori; Fukazawa, Ryuji; Ogawa, Shunichi; Watanabe, Makoto; Fukushima, Yoshimitsu; Kiriyama, Tomonari; Hayashi, Hiromitsu; Itoh, Yasuhiko

2016-01-01

The coronary arterial lesions of Kawasaki disease are mainly dilative lesions, aneurysms, and stenotic lesions formed before, after, and between aneurysms; these lesions develop in multiple branches resulting in complex coronary hemodynamics. Diagnosis of myocardial ischemia and infarction and evaluation of the culprit coronary arteries and regions is critical to evaluating the treatment and prognosis of patients. This study used hybrid imaging, in which multidetector computed tomographic (CT) images for coronary CT angiography (CCTA) and stress myocardial perfusion single-photon emission CT (SPECT) images were fused. We investigated the diagnosis of blood vessels and regions responsible for myocardial ischemia and infarction in patients with complex coronary arterial lesions; in addition, we evaluated myocardial lesions that developed directly under giant coronary artery aneurysms. The subjects were 17 patients with Kawasaki disease with multiple coronary arterial lesions (median age, 18.0 years; 16 male). Both CCTA using 64-row CT and adenosine-loading myocardial SPECT were performed. Three branches, the right coronary artery (RCA), left anterior descending branch (LAD), and left circumflex branch, were evaluated with the conventional side-by-side interpretation, in which the images were lined up for diagnosis, and hybrid imaging, in which the CCTA and SPECT images were fused with computer processing. In addition, the myocardial lesions directly under giant coronary artery aneurysms were investigated with fusion imaging. Images sufficient for evaluation were acquired in all 17 patients. In the RCA, coronary arterial lesions were detected with CCTA in 16 patients. The evaluations were consistent between the side-by-side and fusion interpretation in 14 patients, and the blood vessel responsible for the myocardial ischemic region was identified in 2 patients. In the left circumflex branch, coronary arterial lesions were confirmed with 3-dimensional CT in 5 patients

Pregnancy in women with a history of Kawasaki disease: management and outcomes.

PubMed

Gordon, C T; Jimenez-Fernandez, S; Daniels, L B; Kahn, A M; Tarsa, M; Matsubara, T; Shimizu, C; Burns, J C; Gordon, J B

2014-10-01

To characterise the obstetrical management and outcomes in a series of women with a history of Kawasaki disease (KD) in childhood. Retrospective case series. Tertiary healthcare setting in the USA. Women with a history of KD in childhood. Women completed a detailed health questionnaire and participated in research imaging studies as part of the San Diego Adult KD Collaborative Study. Obstetrical management, complications during pregnancy and delivery, and infant outcomes. Ten women with a history of KD in childhood carried a total of 21 pregnancies to term. There were no cardiovascular complications during labour and delivery despite important cardiovascular abnormalities in four of the ten subjects. Pregnancy was complicated by pre-eclampsia and the post-partum course was complicated by haemorrhage in one subject each. Two of the 21 progeny subsequently developed KD. Women with important cardiovascular sequelae from KD in childhood should be managed by a team that includes both a maternal-fetal medicine specialist and a cardiologist. Pre-pregnancy counselling should include delineation of the woman's current functional and structural cardiovascular status and appropriate adjustment of medications, but excellent outcomes are possible with appropriate care. Review of the English and Japanese literature on KD and pregnancy revealed the occurrence of myocardial infarction during pregnancy in women with missed KD and aneurysms that were not diagnosed until their acute event. Our study highlights the need for counselling with regard to the increased genetic risk of KD in offspring born to these mothers. © 2014 Royal College of Obstetricians and Gynaecologists.

Axillary, Oral and Rectal Routes of Temperature Measurement During Treatment of Acute Kawasaki Disease.

PubMed

Kanegaye, John T; Jones, Jefferson M; Burns, Jane C; Jain, Sonia; Sun, Xiaoying; Jimenez-Fernandez, Susan; Berry, Erika; Pancheri, Joan M; Jaggi, Preeti; Ramilo, Octavio; Tremoulet, Adriana H

2016-01-01

Important therapeutic decisions are made based on the presence or absence of fever in patients with Kawasaki disease (KD), yet no standard method or threshold exists for temperature measurement during the diagnosis and treatment of these patients. We sought to compare surface and internal (rectal or oral) routes of temperature measurement for the detection of fever as a marker of treatment resistance. From a randomized, placebo-controlled trial of infliximab as an adjunct to primary intravenous immunoglobulin treatment for acute KD, we collected concurrent (within 5 minutes) axillary and internal temperature measurements and performed receiver-operating characteristic and Bland-Altman analyses. We also determined the ability of surface temperatures to detect treatment resistance defined by internal temperature measurements. Among 452 oral-axillary and 439 rectal-axillary pairs from 159 patients, mean axillary temperatures were 0.25 and 0.43 °C lower than oral and rectal temperatures and had high receiver-operating characteristic areas under curves. However, axillary temperatures ≥ 38.0 °C had limited sensitivity to detect fever defined by internal temperatures. Axillary thresholds of 37.5 and 37.2 °C provided maximal sensitivity and specificity to detect oral and rectal temperatures ≥ 38.0 °C, respectively. Axillary temperatures are an insensitive metric for fevers defining treatment resistance. Clinical trials should adopt temperature measurement by the oral or rectal routes for adjudication of treatment resistance in KD.

A comparison of efficacy of six prediction models for intravenous immunoglobulin resistance in Kawasaki disease.

PubMed

Qian, Weiguo; Tang, Yunjia; Yan, Wenhua; Sun, Ling; Lv, Haitao

2018-03-09

Kawasaki disease (KD) is the most common pediatric vasculitis. Several models have been established to predict intravenous immunoglobulin (IVIG) resistance. The present study was aimed to evaluate the efficacy of prediction models using the medical data of KD patients. We collected the medical records of patients hospitalized in the Department of Cardiology in Children's Hospital of Soochow University with a diagnosis of KD from Jan 2015 to Dec 2016. IVIG resistance was defined as recrudescent or persistent fever ≥36 h after the end of their IVIG infusion. Patients with IVIG resistance tended to be younger, have higher occurrence of rash and changes of extremities. They had higher levels of c-reactive protein, aspartate aminotransferase, neutrophils proportion (N%), total bilirubin and lower level of albumin. Our prediction model had a sensitivity of 0.72 and a specificity of 0.75. Sensitivity of Kobayashi, Egami, Kawamura, Sano and Formosa were 0.72, 0.44, 0.48, 0.20, and 0.68, respectively. Specificity of these models were 0.62, 0.82, 0.66, 0.91, and 0.48, respectively. Our prediction model had a powerful predictive value in this area, followed by Kobayashi model while all the other prediction models had less excellent performances than ours.

Value of amino-terminal pro B-natriuretic peptide in diagnosing Kawasaki disease.

PubMed

McNeal-Davidson, Ariane; Fournier, Anne; Spigelblatt, Linda; Saint-Cyr, Claire; Mir, Thomas S; Nir, Amiram; Dallaire, Frédéric; Cousineau, Jocelyne; Delvin, Edgard; Dahdah, Nagib

2012-10-01

The aim of the present study was to investigate the diagnostic value of the N-terminal B-type natriuretic peptide (NT-proBNP) in acute Kawasaki disease (KD) given that the clinical criteria and the current basic laboratory tests lack the necessary specificity for accurate diagnosis. Basic biological tests and serum NT-proBNP levels obtained from acute KD patients were compared to that of febrile controls. NT-proBNP was considered abnormal based on the following definitions: above a cut-off determined on receiver operator characteristic (ROC) analysis, above the upper limit for age, or above 2 SD calculated from healthy children. Analyses were also performed for KD cases with complete or incomplete criteria combined and separately. There were 81 patients and 49 controls aged 3.60 ± 2.77 versus 4.25 ± 3.88 years (P= 0.69). ROC analysis yielded significant area under the curve for NT-proBNP. The sensitivity, specificity, positive and negative predictive values were 70.4-88.9%, 69.4-91.8%, 82.8-93.4%, and 65.2-79.1%. The odds ratios based on NT-proBNP definitions varied between 18.13 (95% confidence interval [CI]: 7.21-45.57), 20.82 (95%CI: 8.18-53.0), and 26.71 (95%CI: 8.64-82.57; P < 0.001). Results were reproducible for cases with complete or incomplete criteria separately. NT-proBNP is a reliable marker for the diagnosis of KD. Prospective clinical studies with emphasis on NT-proBNP in a diagnostic algorithm are needed. © 2012 The Authors. Pediatrics International © 2012 Japan Pediatric Society.

Revisiting Kawasaki dynamics in one dimension

NASA Astrophysics Data System (ADS)

Grynberg, M. D.

2010-11-01

Critical exponents of the Kawasaki dynamics in the Ising chain are re-examined numerically through the spectrum gap of evolution operators constructed both in spin and domain-wall representations. At low-temperature regimes the latter provides a rapid finite-size convergence to these exponents, which tend to z≃3.11 for instant quenches under ferromagnetic couplings, while approaching to z≃2 in the antiferro case. The spin representation complements the evaluation of dynamic exponents at higher temperature scales, where the kinetics still remains slow.

Increased Kawasaki Disease Incidence Associated With Higher Precipitation and Lower Temperatures, Japan, 1991-2004.

PubMed

Abrams, Joseph Y; Blase, Jennifer L; Belay, Ermias D; Uehara, Ritei; Maddox, Ryan A; Schonberger, Lawrence B; Nakamura, Yosikazu

2018-06-01

Kawasaki disease (KD) is an acute febrile vasculitis, which primarily affects children. The etiology of KD is unknown; while certain characteristics of the disease suggest an infectious origin, genetic or environmental factors may also be important. Seasonal patterns of KD incidence are well documented, but it is unclear whether these patterns are caused by changes in climate or by other unknown seasonal effects. The relationship between KD incidence and deviations from expected temperature and precipitation were analyzed using KD incidence data from Japanese nationwide epidemiologic surveys (1991-2004) and climate data from 136 weather stations of the Japan Meteorological Agency. Seven separate Poisson-distributed generalized linear regression models were run to examine the effects of temperature and precipitation on KD incidence in the same month as KD onset and the previous 1, 2, 3, 4, 5 and 6 months, controlling for geography as well as seasonal and long-term trends in KD incidence. KD incidence was negatively associated with temperature in the previous 2, 3, 4 and 5 months and positively associated with precipitation in the previous 1 and 2 months. The model that best predicted variations in KD incidence used climate data from the previous 2 months. An increase in total monthly precipitation by 100 mm was associated with increased KD incidence (rate ratio [RR] 1.012, 95% confidence interval [CI]: 1.005-1.019), and an increase of monthly mean temperature by 1°C was associated with decreased KD incidence (RR 0.984, 95% CI: 0.978-0.990). KD incidence was significantly affected by temperature and precipitation in previous months independent of other unknown seasonal factors. Climate data from the previous 2 months best predicted the variations in KD incidence. Although fairly minor, the effect of temperature and precipitation independent of season may provide additional clues to the etiology of KD.

State-of-the-art acute phase management of Kawasaki disease after 2017 scientific statement from the American Heart Association.

PubMed

Liu, Yi-Ching; Lin, Ming-Tai; Wang, Jou-Kou; Wu, Mei-Hwan

2018-03-30

Kawasaki disease (KD) has become the most common form of pediatric systemic vasculitis. Although patients with KD received intravenous immunoglobulin (IVIG) therapy, coronary arterial lesions (CALs) still occurred in 5%-10% of these patients during the acute stage. CALs may persist and even progress to stenosis or obstruction. Therefore, CALs following KD are currently the leading cause of acquired heart diseases in children. The etiology of CALs remains unknown despite more than four decades of research. Two unsolved problems are IVIG unresponsiveness and the diagnosis of incomplete KD. The two subgroups of KD patients with these problems have a high risk of CAL. In April 2017, the American Heart Association (AHA) updated the guidelines for the diagnosis, treatment, and long-term management of KD. Compared with the previous KD guidelines published in 2004, the new guidelines provide solutions to the aforementioned two problems and emphasize risk stratification by using coronary artery Z score systems, as well as coronary severity-based management and long-term follow-up. Therefore, in this study, we merged the AHA Scientific Statement in 2017 with recent findings for Taiwanese KD patients to provide potential future care directions for Taiwanese patients with KD. Copyright © 2018. Published by Elsevier B.V.

Kawasaki Disease (For Parents)

MedlinePlus

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[Development of the community mental health system and activities of the community mental health team in Kawasaki City].

PubMed

Ito, Masato

2012-01-01

Since the 1960s, Kawasaki City has been leading the nation in its efforts regarding community mental health practices. Public institutions such as the Psychiatric Rehabilitation Center in the central area of the city and the Mental Health and Welfare Center in the southern area have mainly developed the psychiatric rehabilitation system. However, since 2000, new mental health needs have emerged, as the target of mental health and welfare services has been diversified to include people with developmental disorders, higher brain dysfunction, or social withdrawal, in addition to those with schizophrenia. Therefore, Kawasaki City's plan for community-based rehabilitation was drawn up, which makes professional support available for individuals with physical, intellectual, and mental disabilities. As the plan was being implemented, in 2008, the Northern Community Rehabilitation Center was established by both the public and private sectors in partnership. After the community mental health teams were assigned to both southern and northern areas of the city, the community partnership has been developed not only for individual support but also for other objectives that required the partnership. Takeshima pointed out that the local community should be inclusive of the psychiatric care in the final stage of community mental health care in Japan. Because of the major policies regarding people with disabilities, the final stage has been reached in the northern area of Kawasaki City. This also leads to improvement in measures for major issues in psychiatry, such as suicide prevention and intervention in psychiatric disease at an early stage.

Remote sensing observation of annual dust cycles and possible causality of Kawasaki disease outbreaks in Japan

PubMed Central

LaHaye, Nick; Linstead, Erik; Sprigg, William A.; Yacoub, Magdi

Kawasaki disease (KD) is a rare vascular disease that, if left untreated, can result in irreparable cardiac damage in children. While the symptoms of KD are well-known, as are best practices for treatment, the etiology of the disease and the factors contributing to KD outbreaks remain puzzling to both medical practitioners and scientists alike. Recently, a fungus known as Candida, originating in the farmlands of China, has been blamed for outbreaks in China and Japan, with the hypothesis that it can be transported over long ranges via different wind mechanisms. This paper provides evidence to understand the transport mechanisms of dust at different geographic locations and the cause of the annual spike of KD in Japan. Candida is carried along with many other dusts, particles or aerosols, of various sizes in major seasonal wind currents. The evidence is based upon particle categorization using the Moderate Resolution Imaging Spectrometer (MODIS) Aerosol Optical Depth (AOD), Fine Mode Fraction (FMF) and Ångström Exponent (AE), the Cloud-Aerosol Lidar and Infrared Pathfinder Satellite Observation (CALIPSO) attenuated backscatter and aerosol subtype, and the Aerosol Robotic Network’s (AERONET) derived volume concentration. We found that seasonality associated with aerosol size distribution at different geographic locations plays a role in identifying dominant abundance at each location. Knowing the typical size of the Candida fungus, and analyzing aerosol characteristics using AERONET data reveals possible particle transport association with KD events at different locations. Thus, understanding transport mechanisms and accurate identification of aerosol sources is important in order to understand possible triggers to outbreaks of KD. This work provides future opportunities to leverage machine learning, including state-of-the-art deep architectures, to build predictive models of KD outbreaks, with the ultimate goal of early forecasting and intervention within a

Role of Interleukin-1 Signaling in a Mouse Model of Kawasaki Disease-Associated Abdominal Aortic Aneurysm.

PubMed

Wakita, Daiko; Kurashima, Yosuke; Crother, Timothy R; Noval Rivas, Magali; Lee, Youngho; Chen, Shuang; Fury, Wen; Bai, Yu; Wagner, Shawn; Li, Debiao; Lehman, Thomas; Fishbein, Michael C; Hoffman, Hal M; Shah, Prediman K; Shimada, Kenichi; Arditi, Moshe

2016-05-01

Kawasaki disease (KD) is the most common cause of acquired cardiac disease in US children. In addition to coronary artery abnormalities and aneurysms, it can be associated with systemic arterial aneurysms. We evaluated the development of systemic arterial dilatation and aneurysms, including abdominal aortic aneurysm (AAA) in the Lactobacillus casei cell-wall extract (LCWE)-induced KD vasculitis mouse model. We discovered that in addition to aortitis, coronary arteritis and myocarditis, the LCWE-induced KD mouse model is also associated with abdominal aorta dilatation and AAA, as well as renal and iliac artery aneurysms. AAA induced in KD mice was exclusively infrarenal, both fusiform and saccular, with intimal proliferation, myofibroblastic proliferation, break in the elastin layer, vascular smooth muscle cell loss, and inflammatory cell accumulation in the media and adventitia. Il1r(-/-), Il1a(-/-), and Il1b(-/-) mice were protected from KD associated AAA. Infiltrating CD11c(+) macrophages produced active caspase-1, and caspase-1 or NLRP3 deficiency inhibited AAA formation. Treatment with interleukin (IL)-1R antagonist (Anakinra), anti-IL-1α, or anti-IL-1β mAb blocked LCWE-induced AAA formation. Similar to clinical KD, the LCWE-induced KD vasculitis mouse model can also be accompanied by AAA formation. Both IL-1α and IL-1β play a key role, and use of an IL-1R blocking agent that inhibits both pathways may be a promising therapeutic target not only for KD coronary arteritis, but also for the other systemic arterial aneurysms including AAA that maybe seen in severe cases of KD. The LCWE-induced vasculitis model may also represent an alternative model for AAA disease. © 2016 American Heart Association, Inc.

Pathogenesis of systemic inflammatory diseases in childhood: "Lessons from clinical trials of anti-cytokine monoclonal antibodies for Kawasaki disease, systemic onset juvenile idiopathic arthritis, and cryopyrin-associated periodic fever syndrome".

PubMed

Yokota, Shumpei; Kikuchi, Masako; Nozawa, Tomo; Kanetaka, Taichi; Sato, Tomomi; Yamazaki, Kazuko; Sakurai, Nodoka; Hara, Ryoki; Mori, Masaaki

2015-01-01

Inflammation has often been considered to be a nonspecific response and to play a bridging role in the activation of adaptive immunity. However, it is now accepted that inflammation is the product of an independent innate immune system closely linked to the adaptive immune system. The key mediators of inflammation are inflammatory cytokines, as determined by multiple lines of evidence both in vitro and in vivo. Due to the crucial role of inflammatory cytokines in the pathogenesis of autoimmune disorders, anti-cytokine treatment has been developed as a therapy for rheumatoid arthritis, juvenile idiopathic arthritis (JIA), and inflammatory bowel diseases. We recently completed several clinical trials of anti-cytokine treatment for children with systemic inflammatory diseases: anti-IL-6 receptor monoclonal antibody (tocilizumab) for children with two subtypes of JIA (poly-JIA and systemic JIA), anti-TNF-α monoclonal antibody (infliximab) for children with Kawasaki disease, and anti-IL-1-β monoclonal antibody (canakinumab) for children with cryopyrin-associated periodic syndrome. This review summarizes the basis of inflammation in terms of innate immunity and adaptive immunity in these systemic inflammatory diseases, clinical efficacy, and tolerability of these biologic agents, and attempts to determine the roles of individual inflammatory cytokines in disease pathogenesis.

Whole genome sequencing of an African American family highlights toll like receptor 6 variants in Kawasaki disease susceptibility.

PubMed

Kim, Jihoon; Shimizu, Chisato; Kingsmore, Stephen F; Veeraraghavan, Narayanan; Levy, Eric; Ribeiro Dos Santos, Andre M; Yang, Hai; Flatley, Jay; Hoang, Long Truong; Hibberd, Martin L; Tremoulet, Adriana H; Harismendy, Olivier; Ohno-Machado, Lucila; Burns, Jane C

2017-01-01

Kawasaki disease (KD) is the most common acquired pediatric heart disease. We analyzed Whole Genome Sequences (WGS) from a 6-member African American family in which KD affected two of four children. We sought rare, potentially causative genotypes by sequentially applying the following WGS filters: sequence quality scores, inheritance model (recessive homozygous and compound heterozygous), predicted deleteriousness, allele frequency, genes in KD-associated pathways or with significant associations in published KD genome-wide association studies (GWAS), and with differential expression in KD blood transcriptomes. Biologically plausible genotypes were identified in twelve variants in six genes in the two affected children. The affected siblings were compound heterozygous for the rare variants p.Leu194Pro and p.Arg247Lys in Toll-like receptor 6 (TLR6), which affect TLR6 signaling. The affected children were also homozygous for three common, linked (r2 = 1) intronic single nucleotide variants (SNVs) in TLR6 (rs56245262, rs56083757 and rs7669329), that have previously shown association with KD in cohorts of European descent. Using transcriptome data from pre-treatment whole blood of KD subjects (n = 146), expression quantitative trait loci (eQTL) analyses were performed. Subjects homozygous for the intronic risk allele (A allele of TLR6 rs56245262) had differential expression of Interleukin-6 (IL-6) as a function of genotype (p = 0.0007) and a higher erythrocyte sedimentation rate at diagnosis. TLR6 plays an important role in pathogen-associated molecular pattern recognition, and sequence variations may affect binding affinities that in turn influence KD susceptibility. This integrative genomic approach illustrates how the analysis of WGS in multiplex families with a complex genetic disease allows examination of both the common disease-common variant and common disease-rare variant hypotheses.

Pyrosequencing Analysis of Norovirus Genogroup II Distribution in Sewage and Oysters: First Detection of GII.17 Kawasaki 2014 in Oysters.

PubMed

Pu, Jian; Kazama, Shinobu; Miura, Takayuki; Azraini, Nabila Dhyan; Konta, Yoshimitsu; Ito, Hiroaki; Ueki, You; Cahyaningrum, Ermaya Eka; Omura, Tatsuo; Watanabe, Toru

2016-12-01

Norovirus GII.3, GII.4, and GII.17 were detected using pyrosequencing in sewage and oysters in January and February 2015, in Japan. The strains in sewage and oyster samples were genetically identical or similar, predominant strains belonging to GII.17 Kawasaki 2014 lineage. This is the first report of GII.17 Kawasaki 2014 in oysters.

Early Differentiation of Kawasaki Disease Shock Syndrome and Toxic Shock Syndrome in a Pediatric Intensive Care Unit.

PubMed

Lin, Ying-Jui; Cheng, Ming-Chou; Lo, Mao-Hung; Chien, Shao-Ju

2015-11-01

Kawasaki disease shock syndrome (KDSS) and toxic shock syndrome (TSS) can present as shock and fever with skin rash, but the management of these 2 groups of patients is different. This report proposes to help clinicians earlier distinguish these 2 diseases and expedite institution of appropriate therapy. We retrospectively reviewed the medical records of patients admitted to the pediatric intensive care unit with the diagnosis of KDSS or TSS from January 2000 through December 2010. Clinical, laboratory and echocardiographic data were collected for analysis of differences between them. Seventeen patients met the inclusion criteria of KDSS and 16 had a confirmed diagnosis of TSS. The mean age of the KDSS group was significantly younger than that of the TSS group (36.8 ± 41.1 vs. 113.3 ± 55.6 months, P < 0.001). Significantly lower hemoglobulin and age-adjusted hemoglobulin concentrations were noted in the KDSS group [Hb, age-adjusted Z score, -1.88 (range, -3.9 to 3.9) vs. 0.89 (range, -6.4 to 10.8), P = 0.006]. The median platelet count of the KDSS group was nearly twice that of the TSS group [312 × 10³ per μL (range, 116-518) vs. 184.5 × 10³ per μL (range: 31-629), P = 0.021]. Echocardiographic abnormalities, such as valvulitis (mitral or tricuspid regurgitation) and coronary artery lesions, were significantly more common in the KDSS group (P = 0.022). Echocardiography, anemia and thrombocytosis are useful early differentiating features between KDSS and TSS patients.

miR-483 Targeting of CTGF Suppresses Endothelial-to-Mesenchymal Transition: Therapeutic Implications in Kawasaki Disease

PubMed Central

He, Ming; Chen, Zhen; Martin, Marcy; Zhang, Jin; Sangwung, Panjamaporn; Woo, Brian; Tremoulet, Adriana H.; Shimizu, Chisato; Jain, Mukesh K.; Burns, Jane C.; Shyy, John Y-J.

2016-01-01

Rationale Endothelial-to-mesenchymal transition (EndoMT) is implicated in myofibroblast-like cell-mediated damage to the coronary arterial wall in acute Kawasaki disease (KD) patients, as evidenced by positive staining for connective tissue growth factor (CTGF) and EndoMT markers in KD autopsy tissues. However, little is known about the molecular basis of EndoMT involved in KD. Objective We investigated the microRNA (miRNA) regulation of CTGF and the consequent EndoMT in KD pathogenesis. As well, the modulation of this process by statin therapy was studied. Methods and Results Sera from healthy children and KD subjects were incubated with human umbilical vein endothelial cells (HUVECs). Cardiovascular disease-related miRNAs, CTGF, and EndoMT markers were quantified using RT-qPCR, ELISA, and Western blotting. Compared to healthy controls, HUVEC incubated with sera from acute KD patients had decreased miR-483, increased CTGF, and increased EndoMT markers. Bioinformatics analysis followed by functional validation demonstrated that Krüppel-like factor 4 (KLF4) transactivates miR-483, which in turn targets the 3′ untranslated region of CTGF mRNA. Overexpression of KLF4 or pre-miR-483 suppressed, whereas knockdown of KLF4 or anti-miR-483 enhanced, CTGF expression in ECs in vitro and in vivo. Furthermore, atorvastatin, currently being tested in a Phase I/IIa clinical trial in KD children, induced KLF4-miR-483, which suppressed CTGF and EndoMT in ECs. Conclusions KD sera suppress the KLF4-miR-483 axis in ECs leading to increased expression of CTGF and induction of EndoMT. This detrimental process in the endothelium may contribute to coronary artery abnormalities in KD patients. Statin therapy may benefit acute KD patients, in part through the restoration of KLF4-miR-483 expression. Clinical Trial Registration NCT01431105 PMID:27923814

A genome-wide association analysis identifies NMNAT2 and HCP5 as susceptibility loci for Kawasaki disease.

PubMed

Kim, Jae-Jung; Yun, Sin Weon; Yu, Jeong Jin; Yoon, Kyung Lim; Lee, Kyung-Yil; Kil, Hong-Ryang; Kim, Gi Beom; Han, Myung-Ki; Song, Min Seob; Lee, Hyoung Doo; Ha, Kee Soo; Sohn, Sejung; Johnson, Todd A; Takahashi, Atsushi; Kubo, Michiaki; Tsunoda, Tatsuhiko; Ito, Kaoru; Onouchi, Yoshihiro; Hong, Young Mi; Jang, Gi Young; Lee, Jong-Keuk

2017-12-01

Kawasaki disease (KD), a systemic vasculitis of infants and children, manifests as fever and mucocutaneous inflammation. Although its etiology is largely unknown, the epidemiological data suggest that genetic factors are important in KD susceptibility. To identify genetic variants influencing KD susceptibility, we performed a genome-wide association study (GWAS) and replication study using a total of 915 children with KD and 4553 controls in the Korean population. Six single-nucleotide polymorphisms (SNPs) in three loci were associated significantly with KD susceptibility (P<1.0 × 10 -5 ), including the previously reported BLK locus (rs6993775, odds ratio (OR)=1.52, P=2.52 × 10 -11 ). The other two loci were newly identified: NMNAT2 on chromosome 1q25.3 (rs2078087, OR=1.33, P=1.15 × 10 -6 ) and the human leukocyte antigen (HLA) region on chromosome 6p21.3 (HLA-C, HLA-B, MICA and HCP5) (rs9380242, rs9378199, rs9266669 and rs6938467; OR=1.33-1.51, P=8.93 × 10 -6 to 5.24 × 10 -8 ). Additionally, SNP rs17280682 in NLRP14 was associated significantly with KD with a family history (18 cases vs 4553 controls, OR=6.76, P=5.46 × 10 -6 ). These results provide new insights into the pathogenesis and pathophysiology of KD.

Marked Acceleration of Atherosclerosis following Lactobacillus casei induced Coronary Arteritis in a Mouse Model of Kawasaki Disease

PubMed Central

Chen, Shuang; Lee, Young Ho; Crother, Timothy R.; Fishbein, Michael; Zhang, Wenxuan; Yilmaz, Atilla; Shimada, Kenichi; Schulte, Danica J; Lehman, Thomas J.A.; Shah, Prediman K.; Arditi, Moshe

2012-01-01

Objective To investigate if Lactobacillus casei cell wall extract (LCWE)-induced Kawasaki Disease (KD) accelerates atherosclerosis in hypercholesterolemic mice. Method and Resuslts Apoe−/− or Ldlr−/− mice were injected with LCWE (KD mice) or PBS, fed high fat diet for 8 weeks, and atherosclerotic lesions in aortic sinuses (AS), arch (AC) and whole aorta were assessed. KD mice had larger, more complex aortic lesions with abundant collagen, and both extracellular and intracellular lipid and foam cells, compared to lesions in control mice despite similar cholesterol levels. Both Apoe−/− KD and Ldlr−/− KD mice showed dramatic acceleration in atherosclerosis vs. controls, with increases in en face aortic atherosclerosis and plaque size in both the AS and AC plaques. Accelerated atherosclerosis was associated with increased circulating IL-12p40, IFN-γ, TNF-α, and increased macrophage, DC, and T cell recruitment in lesions. Furthermore, daily injections of the IL-1Ra, which inhibits LCWE induced KD vasculitis, prevented the acceleration of atherosclerosis. Conclusions Our results suggest an important pathophysiologic link between coronary arteritis/vasculitis in the KD mouse model and subsequent atherosclerotic acceleration, supporting the concept that a similar relation may also be present in KD patients. These results also suggest that KD in childhood may predispose to accelerated and early atherosclerosis as adults. PMID:22628430

Clinical implications in laboratory parameter values in acute Kawasaki disease for early diagnosis and proper treatment.

PubMed

Seo, Yu-Mi; Kang, Hyun-Mi; Lee, Sung-Churl; Yu, Jae-Won; Kil, Hong-Ryang; Rhim, Jung-Woo; Han, Ji-Whan; Lee, Kyung-Yil

2018-05-01

This study aimed to analyse laboratory values according to fever duration, and evaluate the relationship across these values during the acute phase of Kawasaki disease (KD) to aid in the early diagnosis for early-presenting KD and incomplete KD patients. Clinical and laboratory data of patients with KD (n=615) were evaluated according to duration of fever at presentation, and were compared between patients with and without coronary artery lesions (CALs). For evaluation of the relationships across laboratory indices, patients with a fever duration of 5 days or 6 days were used (n=204). The mean fever duration was 6.6±2.3 days, and the proportions of patients with CALs was 19.3% (n=114). C-reactive proteins (CRPs) and neutrophil differential values were highest and hemoglobin, albumin, and lymphocyte differential values were lowest in the 6-day group. Patients with CALs had longer total fever duration, higher CRP and neutrophil differential values and lower hemoglobin and albumin values compared to patients without CALs. CRP, albumin, neutrophil differential, and hemoglobin values at the peak inflammation stage of KD showed positive or negative correlations each other. The severity of systemic inflammation in KD was reflected in the laboratory values including CRP, neutrophil differential, albumin, and hemoglobin. Observing changes in these laboratory parameters by repeated examinations prior to the peak of inflammation in acute KD may aid in diagnosis of early-presenting KD patients.

A national survey on the pediatric cardiologist's clinical approach for patients with Kawasaki disease.

PubMed

Kahwaji, I Y; Connuck, D M; Tafari, N; Dahdah, N S

2002-01-01

In 1994, the American Heart Association (AHA) published the most recent guidelines for long-term cardiovascular management of Kawasaki disease. Since then, recent publications have shed new light on different diagnostic, prognostic, and management issues. We sought the opinion of pediatric cardiologists practicing in U.S. fellowship programs on the subject by means of a multiple-choice survey. Two questions addressed therapy in the acute phase, each preceded by a statement from related literature. Ten duplicate questions addressed the long-term cardiovascular management in five sets of paired questions; each question was first given in reminiscence of a clinical situation and then preceded by a statement from particular publications representative of new information that has become available since the publication of the 1994 AHA guidelines. All questions were provided in the same mailing. Replies were received from 97 participants practicing at 29 institutions. For the acute illness, 21% of respondents do not use high-dose aspirin, and 50% support reassessment of current guidelines. Universal intravenous immune globulin (IVIG) administration is followed by 97%, among whom 20% agree that evaluation of selection criteria is needed. For long-term management, 60-75% advocate regular follow-up of risk level I patients, and 80% favor periodic follow-up, with stress imaging (34-40%), for risk level II. For risk level IV more respondents favor stress echocardiography as opposed to nuclear imaging, in consonance with recent literature. For risk levels III and IV, 36-40% perform coronary angiography on a regular basis, whereas 60% do so when coronary symptoms are present or when stress imaging suggests myocardial ischemia. Finally, 19-25% of respondents do not routinely advise healthy lifestyle to patients free of coronary artery lesions. In conclusion, the guidelines for conventional therapy in the acute phase and long-term cardiovascular management need to be revised.

Analysis of factors associated with development of Bacille Calmette-Guérin inoculation site change in patients with Kawasaki disease.

PubMed

Araki, Tooru; Kodera, Aya; Kitada, Kunimi; Fujiwara, Michimasa; Muraoka, Michiko; Abe, Yoshiko; Ikeda, Masanori; Tsukahara, Hirokazu

2018-04-01

Objective The present study was performed to identify factors associated with a Bacille Calmette-Guérin (BCG) inoculation site change in patients with Kawasaki disease (KD). Methods Among patients who had received BCG vaccination and treatment for KD at our hospital from 2005 through 2016, 177 patients born in 2005 through 2016 were enrolled. The patients were divided into those with (n = 83, change group) and without (n = 94, no-change group) a BCG site change, and the patient demographics, clinical severity, blood examination results, and echocardiographic findings were compared between the two groups. Results The change group was younger at onset and had a shorter interval from vaccination to onset. A BCG site change was observed in patients who developed the onset of KD symptoms from 31 to 806 days after BCG vaccination. Multivariate analysis showed that the interval from vaccination was closely and positively associated with the BCG site change (hazard ratio = 0.995, 95% confidence interval = 0.993-0.997). Conclusion A BCG site change in patients with KD is most closely associated with the interval from BCG vaccination to onset.

Correlation of HAMP gene polymorphisms and expression with the susceptibility and length of hospital stays in Taiwanese children with Kawasaki disease

PubMed Central

Lu, Hsing-Fang; Wong, Henry Sung-Ching; Yu, Hong-Ren; Kuo, Hsing-Chun; Huang, Fu-Chen; Lo, Mao-Hung; Hsieh, Kai-Sheng; Chen, Su-Fen; Chang, Wei-Chiao; Kuo, Ho-Chang

2017-01-01

Kawasaki disease (KD) is a form of systemic vasculitis. Regarding its pathogenesis, HAMP gene encoding hepcidin, which is significant for iron metabolism, has a vital function. In this study, we recruited a total of 381 KD patients for genotyping. Data from 997 subjects (500 subjects from cohort 1; 497 subjects from cohort 2) were used for analysis. Using TaqMan allelic discrimination, we determined five tag SNPs (rs916145, rs10421768, rs3817623, rs7251432, and rs2293689). Treatment outcome data related to such clinical phenotypes as coronary artery lesions (CAL), coronary artery aneurysms (CAA), and intravenous immunoglobulin (IVIG) effects were also collected. Furthermore, we measured plasma hepcidin levels with an enzyme-linked immunosorbent assay. We found that HAMP gene polymorphism (rs7251432, and rs2293689) was significantly correlated with KD risk and that plasma hepcidin levels both before and after IVIG treatment had a significantly positive correlation with length of hospital stays (R = 0.217, p = 0.046 and R = 0.381, p < 0.0001, respectively). In contrast, plasma hepcidin levels has a negative correlation with KD patients’ albumin levels (R = −0.27, p < 0.001) prior to IVIG treatment. This study's findings indicate that HAMP might have a role in the disease susceptibility, as well as its expressions correlated length of hospital stays, and albumin levels in Taiwanese children with KD. PMID:28881695

Genetic epistasis between killer immunoglobulin-like receptors and human leukocyte antigens in Kawasaki disease susceptibility.

PubMed

Bossi, G; Mannarino, S; Pietrogrande, M C; Salice, P; Dellepiane, R M; Cremaschi, A L; Corana, G; Tozzo, A; Capittini, C; De Silvestri, A; Tinelli, C; Pasi, A; Martinetti, M

2015-10-01

Kawasaki disease (KD) is a pediatric acute multisystemic vasculitis complicated by development of coronary artery lesions. The breakthrough theory on KD etiopathogenesis points to pathogens/environmental factors triggered by northeastern wind coming from China. Natural Killer cells and T lymphocytes express the inhibitory/activating Killer Immunoglobulin-like Receptors (KIR) to elicit an immune response against pathogens by binding to human leukocyte antigens (HLA) class I epitopes. We first report on the role of KIR/HLA genetic epistasis in a sample of 100 Italian KD children. We genotyped KIR, HLA-A, HLA-B and HLA-C polymorphisms, and compared KD data with those from 270 Italian healthy donors. The HLA-A*11 ligand for KIR2DS2/2DS4/3DL2 was a KD susceptibility marker by itself (odds ratio (OR)=3.85, confidence interval (CI)=1.55-9.53, P=0.004). Although no epistasis between HLA-A*11 and KIR2DS2/S4 emerged, HLA-A*11 also engages KIR3DL2, a framework gene encoding for a pathogen sensor of CpG-oligodeoxynucleotides (CpG-ODN), and KD blood mononuclear cells are actually prone to pathogen CpG-ODN activation in the acute phase. Moreover, carriers of KIR2DS2/HLA-C1 and KIR2DL2/HLA-C1 were more frequent among KD, in keeping with data demonstrating the involvement of these HLA/KIR couples in autoimmune endothelial damage. The highest KD risk factor was observed among carriers of KIR2DL2 and two or more HLA ligands (OR=10.24, CI=1.87-56.28; P=0.007).

Fine specificities of natural regulatory T cells after IVIG therapy in patients with Kawasaki disease

PubMed Central

Burns, Jane C.; Touma, Ranim; Song, Yali; Padilla, Robert L.; Tremoulet, Adriana H.; Sidney, John; Sette, Alessandro; Franco, Alessandra

2016-01-01

The activation of natural regulatory T cells (nTreg) recognizing the heavy constant region (Fc) of IgG is an important mechanism of action of intravenous immunoglobulin (IVIG) therapy in Kawasaki disease (KD). Lack of circulating Fc-specific nTreg in the sub-acute phase of KD is correlated with the development of coronary artery abnormalities (CAA). Here, we characterize the fine specificity of nTreg in sub-acute (2- to 8-week post-IVIG) and convalescent (1- to 10-year post-IVIG) KD subjects by testing the immunogenicity of 64 peptides, 15 amino acids in length with a 10 amino acid-overlap spanning the entire Fc protein. About 12 Fc peptides (6 pools of 2 consecutive peptides) were recognized by nTreg in the cohorts studied, including two patients with CAA. To test whether IVIG expands the same nTreg populations that maintain vascular homeostasis in healthy subjects, we compared these results with results obtained in healthy adult controls. Similar nTreg fine specificities were observed in KD patients after IVIG and in healthy donors. These results suggest that T cell fitness rather than T cell clonal deletion or anergy is responsible for the lack of Fc-specific nTreg in KD patients who develop CAA. Furthermore, we found that adolescents and adults who had KD during childhood without developing CAA did not respond to the Fc protein in vitro, suggesting that the nTreg response induced by IVIG in KD patients is short-lived. Our results support the concept that peptide epitopes may be a viable therapeutic approach to expand Fc-specific nTreg and more effectively prevent CAA in KD patients. PMID:25822882

Epidemiologic study of Kawasaki disease at a single hospital in Daejeon, Korea (1987 through 2000).

PubMed

Lee, Kyung-Yil; Han, Ji-Whan; Lee, Hyung-Shin; Hong, Ja-Hyun; Hahn, Seung-Hoon; Lee, Joon-Sung; Whang, Kyung-Tai

2004-01-01

We evaluated the epidemiology and a range of clinical characteristics in children with Kawasaki disease (KD) in one area of South Korea. We retrospectively analyzed 506 medical records of children with KD, who were admitted at Daejeon St. Mary's Hospital from January 1987 through December 2000. The mean annual frequency was 36.1 +/- 11.1 cases per year. There were 55 cases (10.9%) in 1993, 50 cases (9.9%) in 1994 and 47 cases (9.3%) in 2000. There was a slightly higher occurrence in summer with no significant difference in seasonal frequency. Age distribution ranged from 2 months to 13 years of age (mean, 2.4 +/- 1.7 years) and 485 children (95.8%) were <5 years of age. The male-to-female ratio was 1.7:1. Of the total cases 0.6% was recurrent, whereas 0.4% occurred between siblings. There were no fatalities. For treatment aspirin alone (65 cases, 12.8%), divided dose intravenous immunoglobulin (IVIG) (400 to 500 mg/day for 4 to 5 days, 231 cases, 45.7%) and one dose IVIG (2.0 g/kg, 210 cases, 41.5%) were used. Between 1996 and 2000, 143 cases were treated with only one dose IVIG, and 21 cases (14.7%) showed coronary artery lesions (CAL). Among the 143 cases 22 cases (15.4%) were retreated with IVIG and/or steroid pulse therapy. The incidence of CAL in this group was 50.0%. In Daejeon, Korea, KD showed slight annual variations without seasonal differences. The rate of CAL in acute stage with one dose IVIG therapy (2 g/kg) was 8.3% in the IVIG responders.

High-density Genotyping of Immune Loci in Kawasaki Disease and IVIG Treatment Response in European-American Case-parent Trio Study

PubMed Central

Shendre, Aditi; Wiener, Howard W.; Zhi, Degui; Vazquez, Ana I; Portman, Michael A.; Shrestha, Sadeep

2014-01-01

Kawasaki disease (KD) is a diffuse and acute small-vessel vasculitis observed in children and has genetic and autoimmune components. We genotyped 112 case-parent trios of European decent (confirmed by AIMS) using the ImmunoChip array and performed association analyses with susceptibility to KD and IVIG non-response. KD susceptibility was assessed using the transmission disequilibrium test whereas IVIG non-response was evaluated using multivariable logistic regression analysis. We replicated SNPs in three gene regions (FCGR, CD40/CDH22, and HLA-DQB2/HLA-DOB) that have been previously associated with KD and provide support to other findings of several novel SNPs in genes with potential pathway in KD pathogenesis. SNP rs838143 in the 3′ UTR of FUT1 gene (2.7×10-5) and rs9847915 in the intergenic region of LOC730109 ∣ BRD7P2 (6.81×10-7) were the top hits for KD susceptibility in additive and dominant models, respectively. The top hits for IVIG responsiveness were rs1200332 in the intergenic region of BAZ1A ∣ C14orf19 (1.4×10-4) and rs4889606 in the intron of the STX1B gene (6.95×10-5) in additive and dominant models, respectively. Our study suggests that genes and biological pathways involved in autoimmune diseases play an important role in the pathogenesis of KD and IVIG response mechanism. PMID:25101798

Anti-inflammatory effect of intravenous immunoglobulin in comparison with dexamethasone in vitro: implication for treatment of Kawasaki disease.

PubMed

Makata, Haruyuki; Ichiyama, Takashi; Uchi, Ryutaro; Takekawa, Tsuyoshi; Matsubara, Tomoyo; Furukawa, Susumu

2006-08-01

High-dose intravenous immunoglobulin (IVIG) is a well-established standard therapy for Kawasaki disease (KD) that reduces the risk of developing coronary artery aneurysms. On the other hand, some reports have recommended an alternative therapy with steroids for KD patients. In this study we investigated the anti-inflammatory effect of IVIG in comparison with dexamethasone at clinical doses in vitro. High-dose IVIG inhibited tumor necrosis factor-alpha (TNF-alpha)-induced activation of nuclear factor-kappaB (NF-kappaB) to a greater degree than dexamethasone in human monocytic U937 cells and human coronary arterial endothelial cells (HCAEC), but not in human T lymphocytic Jurkat cells. IVIG was more potent than dexamethasone in reducing the expression of CD16 (FcgammaRIII) in human monocytic THP-1 cells stimulated with lipopolysaccharide and in Jurkat cells stimulated with dimethyl sulfoxide. In HCAEC exposed to TNF-alpha, IVIG and dexamethasone inhibited interleukin-6 production to a similar degree, whereas the expression of E-selectin was inhibited more strongly by IVIG. Our results show that high-dose IVIG inhibits the activation of monocytes/macrophages and coronary arterial endothelial cells more strongly than that of T cells, whereas dexamethasone inhibits the activation of all three cell types. These findings suggest that IVIG or dexamethasone therapy should be chosen to match the types of cells that are activated during acute KD.

Duration of high-dose aspirin therapy does not affect long-term coronary artery outcomes in Kawasaki disease.

PubMed

Migally, Karl; Braunlin, Elizabeth A; Zhang, Lei; Binstadt, Bryce A

2018-05-02

BackgroundHigh-dose aspirin (HDA) is used with intravenous immunoglobulin (IVIg) in Kawasaki disease (KD). Practice regarding HDA varies, and it is unclear whether HDA duration affects the long-term course.MethodsWe retrospectively studied KD patients at our hospital for over 10 years. Patients were categorized as having received HDA for 0, 1-7, or >7 days. Primary outcome was the maximum coronary Z-score at diagnosis and follow-up; secondary outcomes included inflammatory markers.ResultsOne hundred and three patients had HDA duration documented, of which 35 patients had coronary artery abnormalities (CAAs) at diagnosis. There was no difference in demographics or inflammatory markers between the HDA groups, and no difference in HDA duration between patients with or without CAAs. Seventeen patients received no HDA; they had longer illness and defervescence duration before diagnosis, and were less likely to receive IVIg. For CAAs, multivariate regression revealed that HDA duration did not predict the coronary Z-score at 9-15 months. Higher Z-score at diagnosis was associated with higher Z-score at 9-15 months.ConclusionThe only factor associated with coronary Z-score at 9-15 months was the Z-score at diagnosis. At our institution, longer illness and defervescence duration and the lack of IVIg administration were associated with not administering HDA. HDA duration did not affect the clinically relevant outcomes, particularly CAA persistence.Pediatric Research advance online publication, 2 May 2018; doi:10.1038/pr.2018.44.

Validation study of the Tanaka and Kawasaki equations to estimate the daily sodium excretion by a spot urine sample.

PubMed

Mill, José Geraldo; Rodrigues, Sérgio Lamêgo; Baldo, Marcelo Perim; Malta, Deborah Carvalho; Szwarcwald, Celia Landmann

2015-12-01

To validate Tanaka and Kawasaki's formulas to calculate the salt intake by the sodium/creatinine ratio in spot of urine. Two hundred and seventy two adults (20 - 69 years old; 52.6% women) with 24 h urine collection and two urinary spots collected on the same day (while fasting - spot 1 - or not fasting - spot 2). Anthropometry, blood pressure and fasting blood were measured on the same day. The analysis of agreement between salt consumption measured in the 24 h urine test and urinary spots were determined by the Pearson's correlation (r) and the Bland & Altman method. The mean salt consumption measured by the 24 h sodium excretion was 10.4 ± 5.3 g/day. The correlation between the measured 24 h sodium excretion and the estimation based on spots 1 and 2, respectively, was only moderated according to Tanaka (r = 0.51 and r = 0.55; p < 0.001) and to Kawasaki (r = 0.52 and r = 0.54; p < 0.001). We observed an increasing underestimation of salt consumption by Tanaka to increasing salt consumption and conversely, an overestimation of consumption by the Kawasaki formula. The estimation of salt consumption (difference between measured and calculated salt consumption lower than 1 g/day) was adequate only when the consumption was between 9 - 12 g/day (Tanaka) and 12 - 18 g/day (Kawasaki). Spot urine sampling is adequate to estimate salt consumption only among individuals with an actual consumption near the population mean.

Hepcidin-Induced Iron Deficiency Is Related to Transient Anemia and Hypoferremia in Kawasaki Disease Patients

PubMed Central

Huang, Ying-Hsien; Kuo, Ho-Chang; Huang, Fu-Chen; Yu, Hong-Ren; Hsieh, Kai-Sheng; Yang, Ya-Ling; Sheen, Jiunn-Ming; Li, Sung-Chou; Kuo, Hsing-Chun

2016-01-01

Kawasaki disease (KD) is a type of systemic vasculitis that primarily affects children under the age of five years old. For sufferers of KD, intravenous immunoglobulin (IVIG) has been found to successfully diminish the occurrence of coronary artery lesions. Anemia is commonly found in KD patients, and we have shown that in appropriately elevated hepcidin levels are related to decreased hemoglobin levels in these patients. In this study, we investigated the time period of anemia and iron metabolism during different stages of KD. A total of 100 patients with KD and 20 control subjects were enrolled in this study for red blood cell and hemoglobin analysis. Furthermore, plasma, urine hepcidin, and plasma IL-6 levels were evaluated using enzyme-linked immunosorbent assay in 20 KD patients and controls. Changes in hemoglobin, plasma iron levels, and total iron binding capacity (TIBC) were also measured in patients with KD. Hemoglobin, iron levels, and TIBC were lower (p < 0.001, p = 0.009, and p < 0.001, respectively) while plasma IL-6 and hepcidin levels (both p < 0.001) were higher in patients with KD than in the controls prior to IVIG administration. Moreover, plasma hepcidin levels were positively and significantly correlated with urine hepcidin levels (p < 0.001) prior to IVIG administration. After IVIG treatment, plasma hepcidin and hemoglobin levels significantly decreased (both p < 0.001). Of particular note was a subsequent gradual increase in hemoglobin levels during the three weeks after IVIG treatment; nevertheless, the hemoglobin levels stayed lower in KD patients than in the controls (p = 0.045). These findings provide a longitudinal study of hemoglobin changes and among the first evidence that hepcidin induces transient anemia and hypoferremia during KD’s acute inflammatory phase. PMID:27187366

Tropospheric winds from northeastern China carry the etiologic agent of Kawasaki disease from its source to Japan.

PubMed

Rodó, Xavier; Curcoll, Roger; Robinson, Marguerite; Ballester, Joan; Burns, Jane C; Cayan, Daniel R; Lipkin, W Ian; Williams, Brent L; Couto-Rodriguez, Mara; Nakamura, Yosikazu; Uehara, Ritei; Tanimoto, Hiroshi; Morguí, Josep-Anton

2014-06-03

Evidence indicates that the densely cultivated region of northeastern China acts as a source for the wind-borne agent of Kawasaki disease (KD). KD is an acute, coronary artery vasculitis of young children, and still a medical mystery after more than 40 y. We used residence times from simulations with the flexible particle dispersion model to pinpoint the source region for KD. Simulations were generated from locations spanning Japan from days with either high or low KD incidence. The postepidemic interval (1987-2010) and the extreme epidemics (1979, 1982, and 1986) pointed to the same source region. Results suggest a very short incubation period (<24 h) from exposure, thus making an infectious agent unlikely. Sampling campaigns over Japan during the KD season detected major differences in the microbiota of the tropospheric aerosols compared with ground aerosols, with the unexpected finding of the Candida species as the dominant fungus from aloft samples (54% of all fungal strains). These results, consistent with the Candida animal model for KD, provide support for the concept and feasibility of a windborne pathogen. A fungal toxin could be pursued as a possible etiologic agent of KD, consistent with an agricultural source, a short incubation time and synchronized outbreaks. Our study suggests that the causative agent of KD is a preformed toxin or environmental agent rather than an organism requiring replication. We propose a new paradigm whereby an idiosyncratic immune response, influenced by host genetics triggered by an environmental exposure carried on winds, results in the clinical syndrome known as acute KD.

Tropospheric winds from northeastern China carry the etiologic agent of Kawasaki disease from its source to Japan

PubMed Central

Rodó, Xavier; Curcoll, Roger; Robinson, Marguerite; Ballester, Joan; Burns, Jane C.; Cayan, Daniel R.; Lipkin, W. Ian; Williams, Brent L.; Couto-Rodriguez, Mara; Nakamura, Yosikazu; Uehara, Ritei; Tanimoto, Hiroshi; Morguí, Josep-Anton

2014-01-01

Evidence indicates that the densely cultivated region of northeastern China acts as a source for the wind-borne agent of Kawasaki disease (KD). KD is an acute, coronary artery vasculitis of young children, and still a medical mystery after more than 40 y. We used residence times from simulations with the flexible particle dispersion model to pinpoint the source region for KD. Simulations were generated from locations spanning Japan from days with either high or low KD incidence. The postepidemic interval (1987–2010) and the extreme epidemics (1979, 1982, and 1986) pointed to the same source region. Results suggest a very short incubation period (<24 h) from exposure, thus making an infectious agent unlikely. Sampling campaigns over Japan during the KD season detected major differences in the microbiota of the tropospheric aerosols compared with ground aerosols, with the unexpected finding of the Candida species as the dominant fungus from aloft samples (54% of all fungal strains). These results, consistent with the Candida animal model for KD, provide support for the concept and feasibility of a windborne pathogen. A fungal toxin could be pursued as a possible etiologic agent of KD, consistent with an agricultural source, a short incubation time and synchronized outbreaks. Our study suggests that the causative agent of KD is a preformed toxin or environmental agent rather than an organism requiring replication. We propose a new paradigm whereby an idiosyncratic immune response, influenced by host genetics triggered by an environmental exposure carried on winds, results in the clinical syndrome known as acute KD. PMID:24843117

Coronary artery abnormalities in children with systemic-onset juvenile idiopathic arthritis.

PubMed

Lefèvre-Utile, Alain; Galeotti, Caroline; Koné-Paut, Isabelle

2014-05-01

Still's disease (Systemic-onset Juvenile Idiopathic Arthritis: SoJIA) is characterised by high-spiking daily fevers, arthritis and evanescent rashes. Diagnosis of Still's disease is often challenging. Infectious diseases and other inflammatory conditions, especially in young children, Kawasaki disease may look similar. Clinicians often rely on echocardiographic evidence of coronary artery abnormalities to differentiate between Kawasaki disease and Still's disease. Coronary artery dilation would typically favour the diagnosis of Kawasaki disease. We present four children with Still's disease and coronary artery abnormalities who were initially misdiagnosed as Kawasaki disease. The first patient had pericarditis and an irregular wall of the left coronary artery, without dilation on echocardiography. The second patient had a left coronary artery dilatation and a pericarditis. The third patient had thickened left coronary artery walls, and the fourth patient had a hyperechogenicity of the left and right coronary arteries. They received IVIG without success. The diagnosis of Still's disease was made secondary with evidence of persistent arthritis. All but one patient finally needed biologic treatments. Coronary abnormalities may be observed during various febrile conditions and do not exclude the diagnosis of Still's disease. Copyright © 2013 Société française de rhumatologie. Published by Elsevier SAS. All rights reserved.

Genetics Home Reference: Kawasaki disease

MedlinePlus

... other factors, including changes in other genes, also influence the development of this complex disorder. ... disease appears to be passed through generations in families, but the inheritance pattern is unknown. Children of ...

Information Systems for Government and Business: Trends, Issues, Challenges. Proceedings of the Kawasaki International Seminar on the Information Systems Challenge for Government and Business (2nd, Kawasaki City, Japan, July 21-24, 1987).

ERIC Educational Resources Information Center

United Nations Centre for Regional Development, Nagoya (Japan).

The 25 papers in this proceedings were presented by national and international information systems experts, development planners, and scholars at a seminar that was jointly sponsored by the United Nations Centre for Regional Development and the city of Kawasaki, Japan. Designed to reach a wider group of interested planning practitioners and…

Prediction for Intravenous Immunoglobulin Resistance by Using Weighted Genetic Risk Score Identified From Genome-Wide Association Study in Kawasaki Disease.

PubMed

Kuo, Ho-Chang; Wong, Henry Sung-Ching; Chang, Wei-Pin; Chen, Ben-Kuen; Wu, Mei-Shin; Yang, Kuender D; Hsieh, Kai-Sheng; Hsu, Yu-Wen; Liu, Shih-Feng; Liu, Xiao; Chang, Wei-Chiao

2017-10-01

Intravenous immunoglobulin (IVIG) is the treatment of choice in Kawasaki disease (KD). IVIG is used to prevent cardiovascular complications related to KD. However, a proportion of KD patients have persistent fever after IVIG treatment and are defined as IVIG resistant. To develop a risk scoring system based on genetic markers to predict IVIG responsiveness in KD patients, a total of 150 KD patients (126 IVIG responders and 24 IVIG nonresponders) were recruited for this study. A genome-wide association analysis was performed to compare the 2 groups and identified risk alleles for IVIG resistance. A weighted genetic risk score was calculated by the natural log of the odds ratio multiplied by the number of risk alleles. Eleven single-nucleotide polymorphisms were identified by genome-wide association study. The KD patients were categorized into 3 groups based on their calculated weighted genetic risk score. Results indicated a significant association between weighted genetic risk score (groups 3 and 4 versus group 1) and the response to IVIG (Fisher's exact P value 4.518×10 - 03 and 8.224×10 - 10 , respectively). This is the first weighted genetic risk score study based on a genome-wide association study in KD. The predictive model integrated the additive effects of all 11 single-nucleotide polymorphisms to provide a prediction of the responsiveness to IVIG. © 2017 The Authors.

Identification of Novel Susceptibility Loci for Kawasaki Disease in a Han Chinese Population by a Genome-Wide Association Study

PubMed Central

Huang, Li-Min; Huang, Fu-Yuan; Chiu, Nan-Chang; Chen, Ming-Ren; Chi, Hsin; Lee, Yann-Jinn; Chang, Li-Ching; Liu, Yi-Min; Wang, Hsiang-Hua; Chen, Chien-Hsiun; Chen, Yuan-Tsong; Wu, Jer-Yuarn

2011-01-01

Kawasaki disease (KD) is an acute systemic vasculitis syndrome that primarily affects infants and young children. Its etiology is unknown; however, epidemiological findings suggest that genetic predisposition underlies disease susceptibility. Taiwan has the third-highest incidence of KD in the world, after Japan and Korea. To investigate novel mechanisms that might predispose individuals to KD, we conducted a genome-wide association study (GWAS) in 250 KD patients and 446 controls in a Han Chinese population residing in Taiwan, and further validated our findings in an independent Han Chinese cohort of 208 cases and 366 controls. The most strongly associated single-nucleotide polymorphisms (SNPs) detected in the joint analysis corresponded to three novel loci. Among these KD-associated SNPs three were close to the COPB2 (coatomer protein complex beta-2 subunit) gene: rs1873668 (p = 9.52×10−5), rs4243399 (p = 9.93×10−5), and rs16849083 (p = 9.93×10−5). We also identified a SNP in the intronic region of the ERAP1 (endoplasmic reticulum amino peptidase 1) gene (rs149481, pbest = 4.61×10−5). Six SNPs (rs17113284, rs8005468, rs10129255, rs2007467, rs10150241, and rs12590667) clustered in an area containing immunoglobulin heavy chain variable regions genes, with pbest-values between 2.08×10−5 and 8.93×10−6, were also identified. This is the first KD GWAS performed in a Han Chinese population. The novel KD candidates we identified have been implicated in T cell receptor signaling, regulation of proinflammatory cytokines, as well as antibody-mediated immune responses. These findings may lead to a better understanding of the underlying molecular pathogenesis of KD. PMID:21326860

N-terminal pro-B-type natriuretic peptide diagnostic algorithm versus American Heart Association algorithm for Kawasaki disease.

PubMed

Dionne, Audrey; Meloche-Dumas, Léamarie; Desjardins, Laurent; Turgeon, Jean; Saint-Cyr, Claire; Autmizguine, Julie; Spigelblatt, Linda; Fournier, Anne; Dahdah, Nagib

2017-03-01

Diagnosis of Kawasaki disease (KD) can be challenging in the absence of a confirmatory test or pathognomonic finding, especially when clinical criteria are incomplete. We recently proposed serum N-terminal pro-B-type natriuretic peptide (NT-proBNP) as an adjunctive diagnostic test. We retrospectively tested a new algorithm to help KD diagnosis based on NT-proBNP, coronary artery dilation (CAD) at onset, and abnormal serum albumin or C-reactive protein (CRP). The goal was to assess the performance of the algorithm and compare its performance with that of the 2004 American Heart Association (AHA)/American Academy of Pediatrics (AAP) algorithm. The algorithm was tested on 124 KD patients with NT-proBNP measured on admission at the present institutions between 2007 and 2013. Age at diagnosis was 3.4 ± 3.0 years, with a median of five diagnostic criteria; and 55 of the 124 patients (44%) had incomplete KD. CA complications occurred in 64 (52%), with aneurysm in 14 (11%). Using this algorithm, 120/124 (97%) were to be treated, based on high NT-proBNP alone for 79 (64%); on onset CAD for 14 (11%); and on high CRP or low albumin for 27 (22%). Using the AHA/AAP algorithm, 22/47 (47%) of the eligible patients with incomplete KD would not have been referred for treatment, compared with 3/55 (5%) with the NT-proBNP algorithm (P < 0.001). This NT-proBNP-based algorithm is efficient to identify and treat patients with KD, including those with incomplete KD. This study paves the way for a prospective validation trial of the algorithm. © 2016 Japan Pediatric Society.

Role of the Egami score to predict immunoglobulin resistance in Kawasaki disease among a Western Mediterranean population.

PubMed

Sánchez-Manubens, Judith; Antón, Jordi; Bou, Rosa; Iglesias, Estíbaliz; Calzada-Hernandez, Joan; Borlan, Sergi; Gimenez-Roca, Clara; Rivera, Josefa

2016-07-01

Kawasaki disease is an acute self-limited systemic vasculitis common in childhood. Intravenous immunoglobulin (IVIG) is an effective treatment, and it reduces the incidence of cardiac complications. Egami score has been validated to identify IVIG non-responder patients in Japanese population, and it has shown high sensitivity and specificity to identify these non-responder patients. Although its effectiveness in Japan, Egami score has shown to be ineffective in non-Japanese populations. The aim of this study was to apply the Egami score in a Western Mediterranean population in Catalonia (Spain). Observational population-based study that includes patients from all Pediatric Units in 33 Catalan hospitals, both public and private management, between January 2004 and March 2014. Sensitivity and specificity for the Egami score was calculated, and a logistic regression analysis of predictors of overall response to IVIG was also developed. Predicting IVIG resistance with a cutoff for Egami score ≥3 obtained 26 % sensitivity and 82 % specificity. Negative predictive value was 85 % and positive predictive value 22 %. This low sensitivity implies that three out of four non-responders will not be identified by the Egami score. Besides, logistic regression models did not found significance for the use of the Egami score to predict IVIG resistance in Catalan population although having an area under the ROC curve of 0.618 (IC 95 % 0.538-0.698, p < 0.001). Although regression models found an area under the ROC curve >0.5 to predict IVIG resistance, the low sensitivity excludes the Egami score as a useful tool to predict IVIG resistance in Catalan population.

Human herpes virus type 6 can cause skin lesions at the BCG inoculation site similar to Kawasaki Disease.

PubMed

Kakisaka, Yosuke; Ohara, Tomoichiro; Katayama, Saori; Suzuki, Tasuku; Sasai, Shu; Hino-Fukuyo, Naomi; Kure, Shigeo

2012-12-01

Kawasaki Disease (KD) is acute, febrile, multisystem vasculitis of early childhood, the detailed mechanism of which is still unclear. Skin symptoms occur in KD, such as edema of the hands and feet with subsequent desquamation and redness at the inoculation site of bacillus Calmette-Guerin (BCG). The change at the BCG inoculation site has been considered as a specific feature of KD, although its mechanism is not fully understood. We present an 11-month-old boy who developed fever with redness of the BCG site due to infection with human herpes virus type 6 (HHV6). At the age of 3 months, the patient received BCG. His fever remitted 7 days after the onset of skin redness, with sequential desquamation at the BCG site and extremities, which is not a common feature of HHV6 infection that typically lasts for 3 days. The final diagnosis was exanthema subitum. Characteristically, the HHV6 infection in our patient appeared to be associated with the invigoration of the T cell system, as represented by the elevated serum levels of soluble interleukin-2 receptor (3,490 U/ml vs. normal range 145-519 U/ml). This patient clearly showed redness and crusting at the BCG inoculation site, suggesting that HHV6 infection might cause skin changes similar to those of KD via an unknown mechanism. In addition, we suggest that the activation of the T cell system may account for the skin lesions in KD, characterized by redness and subsequent crusting of the BCG inoculation site and desquamation of the extremities.

Sequence of the toxic shock syndrome toxin gene (tstH) borne by strains of Staphylococcus aureus isolated from patients with Kawasaki syndrome.

PubMed Central

Deresiewicz, R L; Flaxenburg, J; Leng, K; Kasper, D L

1996-01-01

To explore whether a novel staphylococcal clone or structural variant of toxic shock syndrome toxin 1 is associated with Kawasaki syndrome, six toxigenic strains of Staphylococcus aureus from Kawasaki syndrome patients were studied. The strains were divisible into two groups based on phenotypic and genotypic characteristics and are therefore unequivocally not clonal. Portions of the tstH genes of each strain were sequenced. Three were sequenced in their entirety, while the remainder were sequenced from codon 66 to codon 137 of the mature protein only. Two of the former group differed slightly in the sequences of their signal peptides relative to the sequence published for the tstH signal peptide. Those differences did not affect toxin processing or secretion. The sequenced portions of the regions encoding mature toxic shock syndrome toxin 1 were identical in all six strains and corresponded exactly to the published sequence of tstH. No evidence was found for the existence of a structural variant of tstH uniquely associated with Kawasaki syndrome. PMID:8757881

Association of Severity of Coronary Artery Aneurysms in Patients With Kawasaki Disease and Risk of Later Coronary Events.

PubMed

Miura, Masaru; Kobayashi, Tohru; Kaneko, Tetsuji; Ayusawa, Mamoru; Fukazawa, Ryuji; Fukushima, Naoya; Fuse, Shigeto; Hamaoka, Kenji; Hirono, Keiichi; Kato, Taichi; Mitani, Yoshihide; Sato, Seiichi; Shimoyama, Shinya; Shiono, Junko; Suda, Kenji; Suzuki, Hiroshi; Maeda, Jun; Waki, Kenji; Kato, Hitoshi; Saji, Tsutomu; Yamagishi, Hiroyuki; Ozeki, Aya; Tomotsune, Masako; Yoshida, Makiko; Akazawa, Yohei; Aso, Kentaro; Doi, Shouzaburoh; Fukasawa, Yoshi; Furuno, Kenji; Hayabuchi, Yasunobu; Hayashi, Miyuki; Honda, Takafumi; Horita, Norihisa; Ikeda, Kazuyuki; Ishii, Masahiro; Iwashima, Satoru; Kamada, Masahiro; Kaneko, Masahide; Katyama, Hiroshi; Kawamura, Yoichi; Kitagawa, Atushi; Komori, Akiko; Kuraishi, Kenji; Masuda, Hiroshi; Matsuda, Shinichi; Matsuzaki, Satoshi; Mii, Sayaka; Miyamoto, Tomoyuki; Moritou, Yuji; Motoki, Noriko; Nagumo, Kiyoshi; Nakamura, Tsuneyuki; Nishihara, Eiki; Nomura, Yuichi; Ogata, Shohei; Ohashi, Hiroyuki; Okumura, Kenichi; Omori, Daisuke; Sano, Tetsuya; Suganuma, Eisuke; Takahashi, Tsutomu; Takatsuki, Shinichi; Takeda, Atsuhito; Terai, Masaru; Toyono, Manatomo; Watanabe, Kenichi; Watanabe, Makoto; Yamamoto, Masaki; Yamamura, Kenichiro

2018-05-07

Few studies with sufficient statistical power have shown the association of the z score of the coronary arterial internal diameter with coronary events (CE) in patients with Kawasaki disease (KD) with coronary artery aneurysms (CAA). To clarify the association of the z score with time-dependent CE occurrence in patients with KD with CAA. This multicenter, collaborative retrospective cohort study of 44 participating institutions included 1006 patients with KD younger than 19 years who received a coronary angiography between 1992 and 2011. The time-dependent occurrence of CE, including thrombosis, stenosis, obstruction, acute ischemic events, and coronary interventions, was analyzed for small (z score, <5), medium (z score, ≥5 to <10; actual internal diameter, <8 mm), and large (z score, ≥10 or ≥8 mm) CAA by the Kaplan-Meier method. The Cox proportional hazard regression model was used to identify risk factors for CE after adjusting for age, sex, size, morphology, number of CAA, resistance to initial intravenous immunoglobulin (IVIG) therapy, and antithrombotic medications. Of 1006 patients, 714 (71%) were male, 341 (34%) received a diagnosis before age 1 year, 501 (50%) received a diagnosis between age 1 and 5 years, and 157 (16%) received a diagnosis at age 5 years or older. The 10-year event-free survival rate for CE was 100%, 94%, and 52% in men (P < .001) and 100%, 100%, and 75% in women (P < .001) for small, medium, and large CAA, respectively. The CE-free rate was 100%, 96%, and 79% in patients who were not resistant to IVIG therapy (P < .001) and 100%, 96%, and 51% in patients who were resistant to IVIG therapy (P < .001), respectively. Cox regression analysis revealed that large CAA (hazard ratio, 8.9; 95% CI, 5.1-15.4), male sex (hazard ratio, 2.8; 95% CI, 1.7-4.8), and resistance to IVIG therapy (hazard ratio, 2.2; 95% CI, 1.4-3.6) were significantly associated with CE. Classification using the internal diameter z score is useful for

Augmented TLR2 expression on monocytes in both human Kawasaki disease and a mouse model of coronary arteritis.

PubMed

Lin, I-Chun; Kuo, Ho-Chang; Lin, Ying-Jui; Wang, Feng-Shen; Wang, Lin; Huang, Shun-Chen; Chien, Shao-Ju; Huang, Chien-Fu; Wang, Chih-Lu; Yu, Hong-Ren; Chen, Rong-Fu; Yang, Kuender D

2012-01-01

Kawasaki disease (KD) of unknown immunopathogenesis is an acute febrile systemic vasculitis and the leading cause of acquired heart diseases in childhood. To search for a better strategy for the prevention and treatment of KD, this study compared and validated human KD immunopathogenesis in a mouse model of Lactobacillus casei cell wall extract (LCWE)-induced coronary arteritis. Recruited subjects fulfilled the criteria of KD and were admitted for intravenous gamma globulin (IVIG) treatment at the Kaohsiung Chang Gung Memorial Hospital from 2001 to 2009. Blood samples from KD patients were collected before and after IVIG treatment, and cardiovascular abnormalities were examined by transthoracic echocardiography. Wild-type male BALB/c mice (4-week-old) were intraperitoneally injected with LCWE (1 mg/mL) to induce coronary arteritis. The induced immune response in mice was examined on days 1, 3, 7, and 14 post injections, and histopathology studies were performed on days 7 and 14. Both human KD patients and LCWE-treated mice developed coronary arteritis, myocarditis, valvulitis, and pericarditis, as well as elevated plasma levels of interleukin (IL)-2, IL-6, IL-10, monocyte chemoattractant protein (MCP)-1, and tumor necrosis factor (TNF)-α in acute phase. Most of these proinflammatory cytokines declined to normal levels in mice, whereas normal levels were achieved in patients only after IVIG treatment, with a few exceptions. Toll-like receptor (TLR)-2, but not TLR4 surface enhancement on circulating CD14+ monocytes, was augmented in KD patients before IVIG treatment and in LCWE-treated mice, which declined in patients after IVIG treatment. This result suggests that that not only TLR2 augmentation on CD14+ monocytes might be an inflammatory marker for both human KD patients and LCWE-induced CAL mouse model but also this model is feasible for studying therapeutic strategies of coronary arteritis in human KD by modulating TLR2-mediated immune activation on CD14

Augmented TLR2 Expression on Monocytes in both Human Kawasaki Disease and a Mouse Model of Coronary Arteritis

PubMed Central

Lin, I-Chun; Kuo, Ho-Chang; Lin, Ying-Jui; Wang, Feng-Shen; Wang, Lin; Huang, Shun-Chen; Chien, Shao-Ju; Huang, Chien-Fu; Wang, Chih-Lu; Yu, Hong-Ren; Chen, Rong-Fu; Yang, Kuender D.

2012-01-01

Background Kawasaki disease (KD) of unknown immunopathogenesis is an acute febrile systemic vasculitis and the leading cause of acquired heart diseases in childhood. To search for a better strategy for the prevention and treatment of KD, this study compared and validated human KD immunopathogenesis in a mouse model of Lactobacillus casei cell wall extract (LCWE)-induced coronary arteritis. Methods Recruited subjects fulfilled the criteria of KD and were admitted for intravenous gamma globulin (IVIG) treatment at the Kaohsiung Chang Gung Memorial Hospital from 2001 to 2009. Blood samples from KD patients were collected before and after IVIG treatment, and cardiovascular abnormalities were examined by transthoracic echocardiography. Wild-type male BALB/c mice (4-week-old) were intraperitoneally injected with LCWE (1 mg/mL) to induce coronary arteritis. The induced immune response in mice was examined on days 1, 3, 7, and 14 post injections, and histopathology studies were performed on days 7 and 14. Results Both human KD patients and LCWE-treated mice developed coronary arteritis, myocarditis, valvulitis, and pericarditis, as well as elevated plasma levels of interleukin (IL)-2, IL-6, IL-10, monocyte chemoattractant protein (MCP)-1, and tumor necrosis factor (TNF)-α in acute phase. Most of these proinflammatory cytokines declined to normal levels in mice, whereas normal levels were achieved in patients only after IVIG treatment, with a few exceptions. Toll-like receptor (TLR)-2, but not TLR4 surface enhancement on circulating CD14+ monocytes, was augmented in KD patients before IVIG treatment and in LCWE-treated mice, which declined in patients after IVIG treatment. Conclusion This result suggests that that not only TLR2 augmentation on CD14+ monocytes might be an inflammatory marker for both human KD patients and LCWE-induced CAL mouse model but also this model is feasible for studying therapeutic strategies of coronary arteritis in human KD by modulating TLR2

Cardiopulmonary Function, Exercise Capacity, and Echocardiography Finding of Pediatric Patients With Kawasaki Disease

PubMed Central

Tuan, Sheng-Hui; Li, Min-Hui; Hsu, Miao-Ju; Tsai, Yun-Jeng; Chen, Yin-Han; Liao, Tin-Yun; Lin, Ko-Long

2016-01-01

Abstract Coronary artery (CA) abnormalities influence exercise capacity (EC) of patients with Kawasaki disease (KD), and Z-score of CA is a well established method for detecting CA aneurysm. We studied the influence of KD on cardiopulmonary function and EC; meanwhile we analyzed echocardiographic findings of KD patients. We also assessed the correlation between CA Z-score and EC of KD patients to see if CA Z-score of KD patients could reflect EC during exercise. Sixty-three KD patients were recruited as KD group 1 from children (aged 5–18 y) who received transthoracic echocardiographic examinations and symptom-limited treadmill exercise test for regular follow-up of KD from January 2010 to October 2014 in 1 medical center. We then divided KD group 1 into KD group 2 (<5 y, n = 12) and KD group 3 (≥5 y, n = 51) according to time interval between KD onset to when patients received test. Control groups were matched by age, sex, and body mass index. Max-Z of CA was defined as the maximal Z-score of the proximal LCA or RCA by Dalliarre equation or Fuse calculator. All routine parameters measured during standard exercise test were similar between KD and control groups, except that peak rate pressure products (PRPPs) in KD group 1 to 3 were all lower than corresponding control groups significantly (P = 0.010, 0.020, and 0.049, respectively). PRPPs correlated with Max-Z of CA by both equations modest inversely (by Dallaire, P = 0.017, Spearman rho = −0.301; by Fuse, P = 0.014, Spearman rho = −0.309). Our study recruited larger number of KD patients and provided a newer data of EC of KD patients. Our finding suggests that after acute stage of KD, patients could maintain normal cardiorespiratory fitness. Therefore, we believe that it is important to promote cardiovascular health to KD patients and KD patients should exercise as normal peers. However, since KD patients might still have compromised coronary perfusion during exercise, it

Pattern of subcutaneous fat during follow-up of a cohort of North Indian children with Kawasaki disease: a preliminary study.

PubMed

Suthar, Renu; Singh, Surjit; Bhalla, Anil Kumar; Attri, Savita Verma

2014-03-01

Kawasaki disease (KD) has been associated with abnormal lipid profiles. The latter, in turn, have been linked to changes in subcutaneous fat. In this comparative cross-sectional study we have quantified distribution of subcutaneous fat during follow-up of a cohort of North Indian children with KD. We compared 35 KD children (at least 2 years after disease) and 33 healthy controls. Study parameters included weight, height and skinfold thickness (SFT) over biceps, triceps, midaxillary, subscapular, medial calf and suprailiac areas. Waist and hip circumferences were also recorded. All parameters were measured four times at 6-monthly intervals using standardized techniques. Serum lipids were assayed in the study group. Study children were enrolled 3.7 ± 2.5 years after KD and mean age at enrolment was 8.26 ± 3.65 years. Suprailiac SFT measured higher in boys with KD (P ≤ 0.05). Biceps SFT was higher in the study group, but the difference was not significant. Other SFT were not affected. Waist and hip circumference was higher in the study group than controls (P ≤ 0.05). Waist/hip circumference ratio was not affected. Serum low-density lipoprotein cholesterol (LDL-C) and triglycerides were higher in the study group as compared to historical controls (95.60 ± 36.12 and 129.40 ± 64.62 mg/dL vs. 80.10 ± 2.20 and 91.1 ± 29.85; P ≤ 0.05). Total cholesterol and high-density lipoprotein cholesterol levels remained unaffected. Children with KD (especially boys) had increased subcutaneous fat deposition in the suprailiac region and waist, during follow-up. Serum LDL-C and triglycerides were elevated. KD children may have a tendency to develop central obesity. Further studies, with longer follow-up, would be necessary to show whether this has implications for development of coronary artery disease later in life. © 2014 Asia Pacific League of Associations for Rheumatology and Wiley Publishing Asia Pty Ltd.

Building a Natural Language Processing Tool to Identify Patients With High Clinical Suspicion for Kawasaki Disease from Emergency Department Notes.

PubMed

Doan, Son; Maehara, Cleo K; Chaparro, Juan D; Lu, Sisi; Liu, Ruiling; Graham, Amanda; Berry, Erika; Hsu, Chun-Nan; Kanegaye, John T; Lloyd, David D; Ohno-Machado, Lucila; Burns, Jane C; Tremoulet, Adriana H

2016-05-01

Delayed diagnosis of Kawasaki disease (KD) may lead to serious cardiac complications. We sought to create and test the performance of a natural language processing (NLP) tool, the KD-NLP, in the identification of emergency department (ED) patients for whom the diagnosis of KD should be considered. We developed an NLP tool that recognizes the KD diagnostic criteria based on standard clinical terms and medical word usage using 22 pediatric ED notes augmented by Unified Medical Language System vocabulary. With high suspicion for KD defined as fever and three or more KD clinical signs, KD-NLP was applied to 253 ED notes from children ultimately diagnosed with either KD or another febrile illness. We evaluated KD-NLP performance against ED notes manually reviewed by clinicians and compared the results to a simple keyword search. KD-NLP identified high-suspicion patients with a sensitivity of 93.6% and specificity of 77.5% compared to notes manually reviewed by clinicians. The tool outperformed a simple keyword search (sensitivity = 41.0%; specificity = 76.3%). KD-NLP showed comparable performance to clinician manual chart review for identification of pediatric ED patients with a high suspicion for KD. This tool could be incorporated into the ED electronic health record system to alert providers to consider the diagnosis of KD. KD-NLP could serve as a model for decision support for other conditions in the ED. © 2016 by the Society for Academic Emergency Medicine.

Effective therapy with infliximab for clinically mild encephalitis/encephalopathy with a reversible splenial lesion in an infant with Kawasaki disease.

PubMed

Kurokawa, Yoshie; Masuda, Hiroshi; Kobayashi, Tohru; Ono, Hiroshi; Kato, Hitoshi; Imadome, Ken-Ichi; Abe, Jun; Abe, Yuichi; Ito, Shuichi; Ishiguro, Akira

2017-01-01

Kawasaki disease (KD) is a systemic vasculitis in infants. In KD, encephalopathy is rarely (0.1%) associated, however, clinically mild encephalitis/encephalopathy with a reversible splenial lesion (MERS) has previously been reported in some pediatric patients. Here, we report on a 2-year-old girl who had KD complicated with MERS. The patient experienced generalized clonic convulsion and prolonged consciousness disturbance with fever for 2 days. Her head MRI showed a high signal intensity lesion in the splenium of the corpus callosum in diffusion-weighted images, and low apparent diffusion coefficient (ADC) values on day 3. An electroencephalogram showed high voltage slow waves on the occipital and parietal head. On the same day, it was confirmed that the patient showed all the main symptoms of KD. Based on these findings, we diagnosed her with MERS-complicated KD. Even though she was treated with immunoglobulin (total 4 g/kg) and pulsed-dose methylprednisolone, her fever and consciousness disturbance continued, and blood tests showed that inflammation markers remained high. We then treated the patient with infliximab on day 9, and within a few hours of the treatment her fever dropped and all symptoms of KD and consciousness disturbance disappeared. No recurrence of KD or other complications of KD occurred, and she was discharged on day 23. We propose that infliximab is an effective optional treatment for immunoglobulin/glucocorticoid-resistant KD with MERS. To clarify this possibility, further case accumulation is warranted.

A genome-wide association analysis reveals 1p31 and 2p13.3 as susceptibility loci for Kawasaki disease.

PubMed

Kim, Jae-Jung; Hong, Young Mi; Sohn, Saejung; Jang, Gi Young; Ha, Kee-Soo; Yun, Sin Weon; Han, Myung Ki; Lee, Kyung-Yil; Song, Min Seob; Lee, Hyoung Doo; Kim, Dong Soo; Lee, Jong-Eun; Shin, Eun-Soon; Jang, Ji-Hyun; Lee, Yeon-Su; Kim, Sook-Young; Lee, Jong-Young; Han, Bok-Ghee; Wu, Jer-Yuarn; Kim, Kwi-Joo; Park, Young-Mi; Seo, Eul-Joo; Park, In-Sook; Lee, Jong-Keuk

2011-05-01

Kawasaki disease (KD) is an acute self-limited vasculitis of infants and children that manifests as fever and signs of mucocutaneous inflammation. Coronary artery aneurysms develop in approximately 15-25% of untreated children. Although the etiology of KD is largely unknown, epidemiologic data suggest the importance of genetic factors in the susceptibility to KD. In order to identify genetic variants that influence KD susceptibility, we performed a genome-wide association study (GWAS) using Affymetrix SNP array 6.0 in 186 Korean KD patients and 600 healthy controls; 18 and 26 genomic regions with one or more sequence variants were associated with KD and KD with coronary artery lesions (CALs), respectively (p < 1 × 10(-5)). Of these, one locus on chromosome 1p31 (rs527409) was replicated in 266 children with KD and 600 normal controls (odds ratio [OR] = 2.90, 95% confidence interval [CI] = 1.85-4.54, P (combined) = 1.46 × 10(-6)); and a PELI1 locus on chromosome 2p13.3 (rs7604693) was replicated in 86 KD patients with CALs and 600 controls (OR = 2.70, 95% CI = 1.77-4.12, P (combined) = 2.00 × 10(-6)). These results implicate a locus in the 1p31 region and the PELI1 gene locus in the 2p13.3 region as susceptibility loci for KD and CALs, respectively.

CD8+ T Cells Contribute to the Development of Coronary Arteritis in the Lactobacillus casei Cell Wall Extract-Induced Murine Model of Kawasaki Disease.

PubMed

Noval Rivas, Magali; Lee, Youngho; Wakita, Daiko; Chiba, Norika; Dagvadorj, Jargalsaikhan; Shimada, Kenichi; Chen, Shuang; Fishbein, Michael C; Lehman, Thomas J A; Crother, Timothy R; Arditi, Moshe

2017-02-01

Kawasaki disease (KD) is the leading cause of acquired heart disease among children in developed countries. Coronary lesions in KD in humans are characterized by an increased presence of infiltrating CD3+ T cells; however, the specific contributions of the different T cell subpopulations in coronary arteritis development remain unknown. Therefore, we sought to investigate the function of CD4+ and CD8+ T cells, Treg cells, and natural killer (NK) T cells in the pathogenesis of KD. We addressed the function of T cell subsets in KD development by using a well-established murine model of Lactobacillus casei cell wall extract (LCWE)-induced KD vasculitis. We determined which T cell subsets were required for development of KD vasculitis by using several knockout murine strains and depleting monoclonal antibodies. LCWE-injected mice developed coronary lesions characterized by the presence of inflammatory cell infiltrates. Frequently, this chronic inflammation resulted in complete occlusion of the coronary arteries due to luminal myofibroblast proliferation (LMP) as well as the development of coronary arteritis and aortitis. We found that CD8+ T cells, but not CD4+ T cells, NK T cells, or Treg cells, were required for development of KD vasculitis. The LCWE-induced murine model of KD vasculitis mimics many histologic features of the disease in humans, such as the presence of CD8+ T cells and LMP in coronary artery lesions as well as epicardial coronary arteritis. Moreover, CD8+ T cells functionally contribute to the development of KD vasculitis in this murine model. Therapeutic strategies targeting infiltrating CD8+ T cells might be useful in the management of KD in humans. © 2016, American College of Rheumatology.

Influence of Latitude on the Prevalence of Kawasaki Disease: A Retrospective Cohort Study from the Taiwan National Health Insurance Database and Review of the Literature.

PubMed

Chang, Chaw-Liang; Wong, Chih-Shung; Yang, Yi-Chen; Chiu, Nan-Chang

2018-04-25

Background: Countries at higher latitudes have higher incidence rates of Kawasaki disease (KD) than do countries at lower latitudes in the Asian and West Pacific area. However, the precise influence of latitude on KD incidence rates requires further clarification. Methods: We searched the Longitudinal Health Insurance Database 2005 to retrieve patients’ medical records from 1996 to 2009. The patients with KD were categorized as living in northern, middle, and southern Taiwan; the period prevalence of KD for each area was determined. Climate variables, including temperature, sunshine duration, precipitation, and relative humidity, were collected from the Taiwan Central Weather Bureau. The effect of latitude on the period KD prevalence and the correlation between climate variables and KD prevalence were calculated. Results: After patients without complete data excluded, a total of 61,830 children up to 10 years old were retrieved, from which 404 patients with KD were recognized. The period prevalence of KD increased significantly with latitude ( p = 0.0004). Climate variables associated with high temperature demonstrated a connection with KD prevalence; however, this correlation was not statistically significant. Conclusions: Our study demonstrated that higher latitude is associated with a higher KD prevalence in Taiwan.

[Clinical analysis of 942 cases of Kawasaki disease].

PubMed

Zhang, Wei; Li, Qiu; Zhao, Xiao-dong; Tang, Xue-mei; Wang, Xiao-gang; Wang, Mo; Wu, Dao-qi; Ou, Qian; Yang, Xi-qiang

2006-05-01

The study was designed to investigate the clinical characteristics and the effects of therapeutic proposal on Kawasaki disease (KD). Clinical features, diagnosis and treatment for totally 942 patients with KD hospitalized during Jan, 2000 to Dec, 2004 were reviewed. Clinical features of typical and incomplete KD were compared. Also, influential factors for KD resistant to intravenous immune globulin (IVIG) therapy were analyzed. Five hundred and ten cases were followed up for analyzing the prognosis of coronary artery lesion (CAL). (1) 774 cases were diagnosed as typical KD, and 168 cases as incomplete KD. The incidence of infants with incomplete KD was higher than that of infants with typical KD (18.5% vs. 10.1%, P < 0.01). As compared with typical KD, the cases of incomplete KD had a long duration of fever before final diagnosis [(7.7 +/- 2.9) d vs. (7.0 +/- 2.4) d, P < 0.01], high hemoglobin level [Hb, (106.6 +/- 13.4) g/L vs. (103.5 +/- 12.3) g/L, P < 0.01], high hematocrit [Hct, (32.0 +/- 4.3)% vs. (31.0 +/- 4.0)%, P < 0.01], and high prevalence of CAL (23.8% vs. 16.8%, P < 0.05), respectively. The occurrence rate and emerging time of clinical manifestations in incomplete KD and in typical KD were presented, respectively: non-exudative conjunctivitis [occurrence rate, 64.9% vs. 93.5%; emerging time, (4.4 +/- 1.4) d vs. (4.0 +/- 1.6) d, respectively (P < 0.05 or P < 0.01)], erythema and cracking of lips [occurrence rate, 50.6% vs. 94.8%; emerging time, (4.9 +/- 1.4) d vs. (4.5 +/- 1.6) d, respectively (P < 0.05 or P < 0.01)], rash [occurrence rate, 35.1% vs. 87.7%; emerging time, (3.9 +/- 1.9) d vs. (3.4 +/- 1.7) d, respectively (P < 0.05 or P < 0.01)], erythema and edema of extremity [occurrence rate, 26.8% vs. 71.4%; emerging time, (6.7 +/- 1.5) d vs. (5.3 +/- 1.7) d, respectively (P < 0.01)], cervical lymphadenopathy [occurrence rate, 34.5% vs. 68.0%; emerging time, (4.3 +/- 2.5) d vs. (3.6 +/- 2.2) d, respectively (P < 0.05 or P < 0.01)], strawberry tongue

Kawasaki disease and ENSO-driven wind circulation

NASA Astrophysics Data System (ADS)

Ballester, Joan; Burns, Jane C.; Cayan, Dan; Nakamura, Yosikazu; Uehara, Ritei; Rodó, Xavier

2013-05-01

disease (KD) is the most common cause of acquired heart disease in children worldwide. Recently, a climatological study suggested that KD may be triggered by a windborne agent traveling across the north Pacific through the westerly wind flow prevailing at midlatitudes. Here we use KD records to describe the association between enhanced disease activity on opposite sides of the basin and different phases of the El Niño-Southern Oscillation (ENSO) phenomenon, via the linkage to these tropospheric winds. Results show that years with higher-than-normal KD cases in Japan preferentially occur during either El Niño Modoki or La Niña conditions, while in San Diego during the mature phase of El Niño or La Niña events. Given that ENSO offers a degree of predictability at lead times of 6 months, these modulations suggest that seasonal predictions of KD could be used to alert clinicians to periods of increased disease activity.

Treatment response in Kawasaki disease is associated with sialylation levels of endogenous but not therapeutic intravenous immunoglobulin G.

PubMed

Ogata, Shohei; Shimizu, Chisato; Franco, Alessandra; Touma, Ranim; Kanegaye, John T; Choudhury, Biswa P; Naidu, Natasha N; Kanda, Yutaka; Hoang, Long T; Hibberd, Martin L; Tremoulet, Adriana H; Varki, Ajit; Burns, Jane C

2013-01-01

Although intravenous immunoglobulin (IVIG) is highly effective in Kawasaki disease (KD), mechanisms are not understood and 10-20% of patients are treatment-resistant, manifesting a higher rate of coronary artery aneurysms. Murine models suggest that α2-6-linked sialic acid (α2-6Sia) content of IVIG is critical for suppressing inflammation. However, pro-inflammatory states also up-regulate endogenous levels of β-galactoside:α2-6 sialyltransferase-I (ST6Gal-I), the enzyme that catalyzes addition of α2-6Sias to N-glycans. We asked whether IVIG failures correlated with levels of α2-6Sia on infused IVIG or on the patient's own endogenous IgG. We quantified levels of α2-6Sia in infused IVIG and endogenous IgG from 10 IVIG-responsive and 10 resistant KD subjects using multiple approaches. Transcript levels of ST6GAL1, in patient whole blood and B cell lines were evaluated by RT-PCR. Plasma soluble (s)ST6Gal-I levels were measured by ELISA. There was no consistent difference in median sialylation levels of infused IVIG between groups. However, α2-6Sia levels in endogenous IgG, ST6GAL1 transcript levels, and ST6Gal-I protein in serum from IVIG-resistant KD subjects were lower than in responsive subjects at both pre-treatment and one-year time points (p <0.001, respectively). Our data indicate sialylation levels of therapeutic IVIG are unrelated to treatment response in KD. Rather, lower sialylation of endogenous IgG and lower blood levels of ST6GALI mRNA and ST6Gal-I enzyme predict therapy resistance. These differences were stable over time, suggesting a genetic basis. Because IVIG-resistance increases risk of coronary artery aneurysms, our findings have important implications for the identification and treatment of such individuals.

Recurrent Fever Syndromes in Patients After Recovery From Kawasaki Syndrome

PubMed Central

Tremoulet, Adriana H.; Burns, Jane C.; Bastian, John F.; Hoffman, Hal M.

2011-01-01

The recurrence of fever in a child with a history of Kawasaki syndrome (KS) poses a dilemma for clinicians who must consider the possibility of recurrent KS. In this report we present the cases of 4 patients who presented with classical symptoms of KS, were successfully treated with intravenous immunoglobulin, and later experienced a reappearance of inflammatory symptoms in a pattern consistent with a recurrent fever syndrome. The association of these syndromes within the same patient suggests that some patients may have a genetic propensity toward altered immune responses and autoinflammatory syndromes. We propose that these 2 syndromes exist within a family of febrile disorders related to innate immune dysregulation. PMID:21220401

Ophthalmologic complications of systemic disease.

PubMed

Klig, Jean E

2008-02-01

The human eye, as an organ, can offer critical clues to the presence of systemic disease. This article discusses the various ophthalmologic manifestations of systemic disease that can be evident on examination by an emergency department provider, as well as some findings that can be discerned with specialty consultation. The following topics are reviewed with respect to potential ocular signs and complications: syphilis, herpes zoster, Lyme disease, acquired immunodeficiency syndrome, Reiter's syndrome, Kawasaki's disease, temporal arteritis, endocarditis, hypertension, and diabetes mellitus. Indications for emergent ophthalmologic consultation are also emphasized.

Replication and meta-analysis of GWAS identified susceptibility loci in Kawasaki disease confirm the importance of B lymphoid tyrosine kinase (BLK) in disease susceptibility.

PubMed

Chang, Chia-Jung; Kuo, Ho-Chang; Chang, Jeng-Sheng; Lee, Jong-Keuk; Tsai, Fuu-Jen; Khor, Chiea Chuen; Chang, Li-Ching; Chen, Shih-Ping; Ko, Tai-Ming; Liu, Yi-Min; Chen, Ying-Ju; Hong, Young Mi; Jang, Gi Young; Hibberd, Martin L; Kuijpers, Taco; Burgner, David; Levin, Michael; Burns, Jane C; Davila, Sonia; Chen, Yuan-Tsong; Chen, Chien-Hsiun; Wu, Jer-Yuarn; Lee, Yi-Ching

2013-01-01

The BLK and CD40 loci have been associated with Kawasaki disease (KD) in two genome-wide association studies (GWAS) conducted in a Taiwanese population of Han Chinese ancestry (Taiwanese) and in Japanese cohorts. Here we build on these findings with replication studies of the BLK and CD40 loci in populations of Korean and European descent. The BLK region was significantly associated with KD susceptibility in both populations. Within the BLK gene the rs2736340-located linkage disequilibrium (LD ) comprising the promoter and first intron was strongly associated with KD, with the combined results of Asian studies including Taiwanese, Japanese, and Korean populations (2,539 KD patients and 7,021 controls) providing very compelling evidence of association (rs2736340, OR = 1.498, 1.354-1.657; P = 4.74×10(-31)). We determined the percentage of B cells present in the peripheral blood mononuclear cell (PBMC) population and the expression of BLK in the peripheral blood leukocytes (leukocytes) of KD patients during the acute and convalescent stages. The percentage of B cells in the PBMC population and the expression of BLK in leukocytes were induced in patients in the acute stage of KD. In B cell lines derived from KD patients, and in purified B cells from KD patients obtained during the acute stage, those with the risk allele of rs2736340 expressed significantly lower levels of BLK. These results suggest that peripheral B cells play a pathogenic role during the acute stage of KD. Decreased BLK expression in peripheral blood B cells may alter B cell function and predispose individuals to KD. These associative data suggest a role for B cells during acute KD. Understanding the functional implications may facilitate the development of B cell-mediated therapy for KD.

Kawasaki Disease-Specific Molecules in the Sera Are Linked to Microbe-Associated Molecular Patterns in the Biofilms

PubMed Central

Murata, Kenji; Kanno, Shunsuke; Nishio, Hisanori; Saito, Mitsumasa; Tanaka, Tamami; Yamamura, Kenichiro; Sakai, Yasunari; Takada, Hidetoshi; Miyamoto, Tomofumi; Mizuno, Yumi; Ouchi, Kazunobu; Waki, Kenji; Hara, Toshiro

2014-01-01

Background Kawasaki disease (KD) is a systemic vasculitis of unknown etiology. The innate immune system is involved in its pathophysiology at the acute phase. We have recently established a novel murine model of KD coronary arteritis by oral administration of a synthetic microbe-associated molecular pattern (MAMP). On the hypothesis that specific MAMPs exist in KD sera, we have searched them to identify KD-specific molecules and to assess the pathogenesis. Methods We performed liquid chromatography-mass spectrometry (LC-MS) analysis of fractionated serum samples from 117 patients with KD and 106 controls. Microbiological and LC-MS evaluation of biofilm samples were also performed. Results KD samples elicited proinflammatory cytokine responses from human coronary artery endothelial cells (HCAECs). By LC-MS analysis of KD serum samples collected at 3 different periods, we detected a variety of KD-specific molecules in the lipophilic fractions that showed distinct m/z and MS/MS fragmentation patterns in each cluster. Serum KD-specific molecules showed m/z and MS/MS fragmentation patterns almost identical to those of MAMPs obtained from the biofilms formed in vitro (common MAMPs from Bacillus cereus, Yersinia pseudotuberculosis and Staphylococcus aureus) at the 1st study period, and from the biofilms formed in vivo (common MAMPs from Bacillus cereus, Bacillus subtilis/Bacillus cereus/Yersinia pseudotuberculosis and Staphylococcus aureus) at the 2nd and 3rd periods. The biofilm extracts from Bacillus cereus, Bacillus subtilis, Yersinia pseudotuberculosis and Staphylococcus aureus also induced proinflammatory cytokines by HCAECs. By the experiments with IgG affinity chromatography, some of these serum KD-specific molecules bound to IgG. Conclusions We herein conclude that serum KD-specific molecules were mostly derived from biofilms and possessed molecular structures common to MAMPs from Bacillus cereus, Bacillus subtilis, Yersinia pseudotuberculosis and Staphylococcus

Discovering disease associations by integrating electronic clinical data and medical literature.

PubMed

Holmes, Antony B; Hawson, Alexander; Liu, Feng; Friedman, Carol; Khiabanian, Hossein; Rabadan, Raul

2011-01-01

Electronic health record (EHR) systems offer an exceptional opportunity for studying many diseases and their associated medical conditions within a population. The increasing number of clinical record entries that have become available electronically provides access to rich, large sets of patients' longitudinal medical information. By integrating and comparing relations found in the EHRs with those already reported in the literature, we are able to verify existing and to identify rare or novel associations. Of particular interest is the identification of rare disease co-morbidities, where the small numbers of diagnosed patients make robust statistical analysis difficult. Here, we introduce ADAMS, an Application for Discovering Disease Associations using Multiple Sources, which contains various statistical and language processing operations. We apply ADAMS to the New York-Presbyterian Hospital's EHR to combine the information from the relational diagnosis tables and textual discharge summaries with those from PubMed and Wikipedia in order to investigate the co-morbidities of the rare diseases Kaposi sarcoma, toxoplasmosis, and Kawasaki disease. In addition to finding well-known characteristics of diseases, ADAMS can identify rare or previously unreported associations. In particular, we report a statistically significant association between Kawasaki disease and diagnosis of autistic disorder.

Discovering Disease Associations by Integrating Electronic Clinical Data and Medical Literature

PubMed Central

Holmes, Antony B.; Hawson, Alexander; Liu, Feng; Friedman, Carol; Khiabanian, Hossein; Rabadan, Raul

2011-01-01

Electronic health record (EHR) systems offer an exceptional opportunity for studying many diseases and their associated medical conditions within a population. The increasing number of clinical record entries that have become available electronically provides access to rich, large sets of patients' longitudinal medical information. By integrating and comparing relations found in the EHRs with those already reported in the literature, we are able to verify existing and to identify rare or novel associations. Of particular interest is the identification of rare disease co-morbidities, where the small numbers of diagnosed patients make robust statistical analysis difficult. Here, we introduce ADAMS, an Application for Discovering Disease Associations using Multiple Sources, which contains various statistical and language processing operations. We apply ADAMS to the New York-Presbyterian Hospital's EHR to combine the information from the relational diagnosis tables and textual discharge summaries with those from PubMed and Wikipedia in order to investigate the co-morbidities of the rare diseases Kaposi sarcoma, toxoplasmosis, and Kawasaki disease. In addition to finding well-known characteristics of diseases, ADAMS can identify rare or previously unreported associations. In particular, we report a statistically significant association between Kawasaki disease and diagnosis of autistic disorder. PMID:21731656

Kawasaki disease and toxic shock syndrome--at last the etiology is clear?

PubMed

Curtis, Nigel

2004-01-01

A decade after the superantigen hypothesis for KD was first suggested, it has still not been either proven or refuted conclusively. Although initial optimism for the hypothesis was quashed by a series of published papers apparently refuting the idea, in the last few years there have been a number of good studies providing evidence in support of the superantigen hypothesis. Whether this renewed enthusiasm is justified will hopefully become clear in the near future. Ultimately, accurate diagnosis, more targeted treatment, and preventative strategies depend on the unraveling of the immunopathogenesis of this disease.

Treatment Response in Kawasaki Disease Is Associated with Sialylation Levels of Endogenous but Not Therapeutic Intravenous Immunoglobulin G

PubMed Central

Ogata, Shohei; Shimizu, Chisato; Franco, Alessandra; Touma, Ranim; Kanegaye, John T.; Choudhury, Biswa P.; Naidu, Natasha N.; Kanda, Yutaka; Hoang, Long T.; Hibberd, Martin L.; Tremoulet, Adriana H.; Varki, Ajit; Burns, Jane C.

2013-01-01

Objectives Although intravenous immunoglobulin (IVIG) is highly effective in Kawasaki disease (KD), mechanisms are not understood and 10-20% of patients are treatment-resistant, manifesting a higher rate of coronary artery aneurysms. Murine models suggest that α2-6-linked sialic acid (α2-6Sia) content of IVIG is critical for suppressing inflammation. However, pro-inflammatory states also up-regulate endogenous levels of β-galactoside:α2-6 sialyltransferase-I (ST6Gal-I), the enzyme that catalyzes addition of α2-6Sias to N-glycans. We asked whether IVIG failures correlated with levels of α2-6Sia on infused IVIG or on the patient’s own endogenous IgG. Methods We quantified levels of α2-6Sia in infused IVIG and endogenous IgG from 10 IVIG-responsive and 10 resistant KD subjects using multiple approaches. Transcript levels of ST6GAL1, in patient whole blood and B cell lines were evaluated by RT-PCR. Plasma soluble (s)ST6Gal-I levels were measured by ELISA. Results There was no consistent difference in median sialylation levels of infused IVIG between groups. However, α2-6Sia levels in endogenous IgG, ST6GAL1 transcript levels, and ST6Gal-I protein in serum from IVIG-resistant KD subjects were lower than in responsive subjects at both pre-treatment and one-year time points (p <0.001, respectively). Conclusions Our data indicate sialylation levels of therapeutic IVIG are unrelated to treatment response in KD. Rather, lower sialylation of endogenous IgG and lower blood levels of ST6GALI mRNA and ST6Gal-I enzyme predict therapy resistance. These differences were stable over time, suggesting a genetic basis. Because IVIG-resistance increases risk of coronary artery aneurysms, our findings have important implications for the identification and treatment of such individuals. PMID:24324693

Kawasaki Disease

MedlinePlus

... Life Family Life Family Life Medical Home Family Dynamics Media Work & Play Getting Involved in Your Community ... and Urinary Tract Glands & Growth Head Neck & Nervous System Heart Infections Learning Disabilities Obesity Orthopedic Prevention Sexually ...

Reassessment of carotid intima-media thickness by standard deviation score in children and adolescents after Kawasaki disease.

PubMed

Noto, Nobutaka; Kato, Masataka; Abe, Yuriko; Kamiyama, Hiroshi; Karasawa, Kensuke; Ayusawa, Mamoru; Takahashi, Shori

2015-01-01

Previous studies that used carotid ultrasound have been largely conflicting in regards to whether or not patients after Kawasaki disease (KD) have a greater carotid intima-media thickness (CIMT) than controls. To test the hypothesis that there are significant differences between the values of CIMT expressed as absolute values and standard deviation scores (SDS) in children and adolescents after KD and controls, we reviewed 12 published articles regarding CIMT on KD patients and controls. The mean ± SD of absolute CIMT (mm) in the KD patients and controls obtained from each article was transformed to SDS (CIMT-SDS) using age-specific reference values established by Jourdan et al. (J: n = 247) and our own data (N: n = 175), and the results among these 12 articles were compared between the two groups and the references for comparison of racial disparities. There were no significant differences in mean absolute CIMT and mean CIMT-SDS for J between KD patients and controls (0.46 ± 0.06 mm vs. 0.44 ± 0.04 mm, p = 0.133, and 1.80 ± 0.84 vs. 1.25 ± 0.12, p = 0.159, respectively). However, there were significant differences in mean CIMT-SDS for N between KD patients and controls (0.60 ± 0.71 vs. 0.01 ± 0.65, p = 0.042). When we assessed the nine articles on Asian subjects, the difference of CIMT-SDS between the two groups was invariably significant only for N (p = 0.015). Compared with the reference values, CIMT-SDS of controls was within the normal range at a rate of 41.6 % for J and 91.6 % for N. These results indicate that age- and race-specific reference values for CIMT are mandatory for performing accurate assessment of the vascular status in healthy children and adolescents, particularly in those after KD considered at increased long-term cardiovascular risk.

Cardiopulmonary Function, Exercise Capacity, and Echocardiography Finding of Pediatric Patients With Kawasaki Disease: An Observational Study.

PubMed

Tuan, Sheng-Hui; Li, Min-Hui; Hsu, Miao-Ju; Tsai, Yun-Jeng; Chen, Yin-Han; Liao, Tin-Yun; Lin, Ko-Long

2016-01-01

Coronary artery (CA) abnormalities influence exercise capacity (EC) of patients with Kawasaki disease (KD), and Z-score of CA is a well established method for detecting CA aneurysm. We studied the influence of KD on cardiopulmonary function and EC; meanwhile we analyzed echocardiographic findings of KD patients. We also assessed the correlation between CA Z-score and EC of KD patients to see if CA Z-score of KD patients could reflect EC during exercise.Sixty-three KD patients were recruited as KD group 1 from children (aged 5-18 y) who received transthoracic echocardiographic examinations and symptom-limited treadmill exercise test for regular follow-up of KD from January 2010 to October 2014 in 1 medical center. We then divided KD group 1 into KD group 2 (<5 y, n = 12) and KD group 3 (≥5 y, n = 51) according to time interval between KD onset to when patients received test. Control groups were matched by age, sex, and body mass index. Max-Z of CA was defined as the maximal Z-score of the proximal LCA or RCA by Dalliarre equation or Fuse calculator.All routine parameters measured during standard exercise test were similar between KD and control groups, except that peak rate pressure products (PRPPs) in KD group 1 to 3 were all lower than corresponding control groups significantly (P = 0.010, 0.020, and 0.049, respectively). PRPPs correlated with Max-Z of CA by both equations modest inversely (by Dallaire, P = 0.017, Spearman rho = -0.301; by Fuse, P = 0.014, Spearman rho = -0.309).Our study recruited larger number of KD patients and provided a newer data of EC of KD patients. Our finding suggests that after acute stage of KD, patients could maintain normal cardiorespiratory fitness. Therefore, we believe that it is important to promote cardiovascular health to KD patients and KD patients should exercise as normal peers. However, since KD patients might still have compromised coronary perfusion during exercise, it remains crucial to

Computer-assisted initial diagnosis of rare diseases

PubMed Central

Piñol, Marc; Vilaplana, Jordi; Teixidó, Ivan; Cruz, Joaquim; Comas, Jorge; Vilaprinyo, Ester; Sorribas, Albert

2016-01-01

Introduction. Most documented rare diseases have genetic origin. Because of their low individual frequency, an initial diagnosis based on phenotypic symptoms is not always easy, as practitioners might never have been exposed to patients suffering from the relevant disease. It is thus important to develop tools that facilitate symptom-based initial diagnosis of rare diseases by clinicians. In this work we aimed at developing a computational approach to aid in that initial diagnosis. We also aimed at implementing this approach in a user friendly web prototype. We call this tool Rare Disease Discovery. Finally, we also aimed at testing the performance of the prototype. Methods. Rare Disease Discovery uses the publicly available ORPHANET data set of association between rare diseases and their symptoms to automatically predict the most likely rare diseases based on a patient’s symptoms. We apply the method to retrospectively diagnose a cohort of 187 rare disease patients with confirmed diagnosis. Subsequently we test the precision, sensitivity, and global performance of the system under different scenarios by running large scale Monte Carlo simulations. All settings account for situations where absent and/or unrelated symptoms are considered in the diagnosis. Results. We find that this expert system has high diagnostic precision (≥80%) and sensitivity (≥99%), and is robust to both absent and unrelated symptoms. Discussion. The Rare Disease Discovery prediction engine appears to provide a fast and robust method for initial assisted differential diagnosis of rare diseases. We coupled this engine with a user-friendly web interface and it can be freely accessed at http://disease-discovery.udl.cat/. The code and most current database for the whole project can be downloaded from https://github.com/Wrrzag/DiseaseDiscovery/tree/no_classifiers. PMID:27547534

Weight and the vitamin K expoxide reductase 1 genotype primarily contribute to the warfarin dosing in pediatric patients with Kawasaki disease.

PubMed

Wang, Zhouping; Zhang, Li; Huang, Ping; Gu, Xiaoqiong; Xie, Xiaofei; Wang, Yanfei; Li, Wei; Zeng, Qiyi

2018-05-08

Warfarin therapy is recommended in children with giant coronary artery aneurysms (GCAAs) after Kawasaki disease (KD). Large individual variability makes it difficult to predict the warfarin dose. Polymorphisms in the vitamin K expoxide reductase 1 (VKORC1) and cytochrome P4502C9 (CYP2C9) genes have been reported to influence the warfarin dose. We investigated the effects of the VKORC1 and CYP2C9 genotypes on the warfarin dose in pediatric patients with giant CAAs after KD. We attempted to create a dosing algorithm. The clinical and genetic data of patients were documented. VKORC1 (rs 9923231) and CYP2C9 *3 (rs 1057910) were genotyped using TaqMan real-time polymerase chain reaction. A linear regression analysis was performed to evaluate the contribution of clinical and genetic factors to the warfarin maintenance dose. Forty-seven patients were enrolled. Patients with the CT or CC genotype of VKORC1 had a relatively higher warfarin dose than did those with the TT genotype (p < 0.05). Three patients with CYP2C9*1/*3 had a lower warfarin dose than did those with the wild CYP2C9*1/*1 genotype, but the difference did not reach significance (p > 0.05). Weight and the VKORC1 genotype predominantly contributed to the warfarin dose, with 33.0% and 11.2% of variability, respectively. The observed warfarin dose was correlated with the predicted dose based on the algorithm used in our study (r = 0.45, p < 0.01). Weight and the VKORC1 genotype primarily determined the warfarin dose in Chinese pediatric patients with KD. Further studies are warranted to verify the findings of our study. Copyright © 2018 Elsevier Ltd. All rights reserved.

Mid-term Risk for Subclinical Atherosclerosis and Chronic Myocarditis in Children with Kawasaki Disease and Transient Coronary Abnormalities.

PubMed

Parihar, Mansingh; Singh, Surjit; Vignesh, Pandiarajan; Gupta, Anju; Rohit, Manojkumar

2017-08-01

There is evidence for premature atherosclerosis and systemic arterial stiffening during follow-up of children with Kawasaki disease (KD) and coronary artery abnormalities (CAA). Moreover, patients with KD may also have subclinical myocardial involvement and inhomogeneous ventricular repolarization. The inhomogeneous ventricular repolarization manifests as increased QT dispersion on electrocardiography. There is a paucity of studies in endothelial dysfunction and QT dispersion in children with KD and transient CAA. Twenty children with KD and transient CAA were studied at least 1 year after resolution of CAA. Mean follow-up period between KD onset and enrolment in the study was 53.7 months. Twenty age and sex-matched controls were enrolled. High-resolution B-mode ultrasonography was used to analyze brachial artery dilatation in response to reactive hyperemia (cases and controls) and sublingual nitroglycerine (cases only). Carotid artery intima-media thickness (cIMT) and stiffness index were calculated. The difference between maximum and minimum QTc intervals on 12 lead electrocardiogram was calculated as QTc dispersion (QTcd). No statistically significant difference was noted in percent flow-mediated dilatation of brachial arteries in response to reactive hyperemia between cases (13.31 ± 10.41%) and controls (12.86 ± 7.09%). Sublingual nitroglycerine-mediated dilatation in children with KD was 14.88 ± 12.03%. Mean cIMT was similar in cases (0.036 ± 0.015 cm) and controls (0.035 ± 0.076 cm; p = 0.791). No statistically significant difference between groups was observed in mean QTcd values (0.057 ± 0.018 s vs. 0.059 ± 0.015 s in controls, p = 0.785). No evidence of significant endothelial dysfunction or increased QT dispersion in patients with KD and transient coronary artery abnormalities was found in our cohort when studied at a mean follow-up of 53.7 months. This is reassuring, and indicates that risk of subclinical atherosclerosis

Addison disease - diagnosis and initial management.

PubMed

O'Connell, Susan; Siafarikas, Aris

2010-11-01

Adrenal insufficiency is a rare disease caused by either primary adrenal failure (Addison disease) or by impairment of the hypothalamic-pituitary-adrenal axis. Steroid replacement therapy normalises quality of life, however, adherence can be problematic. This article provides information on adrenal insufficiency focusing on awareness of initial symptoms and on risk scenarios, emergency management and baseline investigations, complete investigations and long term management. Early recognition of adrenal insufficiency is essential to avoid associated morbidity and mortality. Initial diagnosis and decision to treat are based on history and physical examination. Appropriate management includes emergency resuscitation and steroid administration. Initial investigations can include sodium, potassium and blood glucose levels. However, complete investigations can be deferred. Specialist advice should be obtained and long term management includes a Team Care Arrangement. For patients, an emergency plan and emergency identification are essential.

Quantitative assessment of urban and industrial symbiosis in Kawasaki, Japan.

PubMed

Van Berkel, Rene; Fujita, Tsuyoshi; Hashimoto, Shizuka; Fujii, Minoru

2009-03-01

Colocated firms can achieve environmental benefit and competitive advantage from exchanging physical resources (known as industrial symbiosis) with each other or with residential areas (referenced here as urban symbiosis). Past research illustrated that economic and environmental benefits appear self-evident, although detailed quantification has only been attempted of symbioses for energy and water utilities. This article provides a complimentary case studyfor Kawasaki, Japan. The 14 documented symbioses connect steel, cement, chemical, and paperfirms and their spin-off recycling businesses. Seven key material exchanges divert annually at least 565 000 tons of waste from incineration or landfill. Four of these collectively present an estimated economic opportunity of 13.3 billion JPY (approximately 130 million USD) annually. Five symbioses involve utilization of byproduct and two sharing of utilities. The others are traditional or new recycling industries that do not specifically benefit from geographic proximity. The synergistic effect of urban and industrial symbiosis is unique. The legislative framework for a recycling-oriented society has contributed to realization of the symbioses, as has the availability of government subsidies through the Eco-Town program.

Carotid Intima-Media Thickness and Lipid Profile in Children With Kawasaki Disease: A Single-Center Follow-up Study After a Mean Duration of 6.9 Years.

PubMed

Gopalan, Kavitha; Singh, Surjit; Vignesh, Pandiarajan; Gupta, Anju; Rohit, Manojkumar; Attri, Savita Verma

2018-03-13

Kawasaki disease (KD) has a predilection to involve coronary arteries, leading to several long-term cardiovascular sequelae. Apart from coronary artery abnormalities, children with KD are also prone to develop premature atherosclerosis, endothelial dysfunction, and lipid abnormalities. Some of these complications may occur even in children who have received appropriate treatment with intravenous immunoglobulin in the acute phase. In 2009, we had studied carotid intima-media thickness (cIMT) and lipid profile in 27 children with KD at least 1 year after the acute episode. In the present study, we have followed up the same cohort of 27 children at least 5 years after the acute episode of KD. We measured the cIMT, a surrogate marker for premature atherosclerosis, and fasting lipid profile in the cohort and compared the results with values obtained in our previous study. There was significantly higher mean cIMT in children with KD as compared with control subjects. However, there was no significant difference in cIMT among children in the cohort at 1 and 5 years of follow-up. Abnormal lipid profile was seen in 7 of 27 children in the present study, 5 of whom also had had lipid abnormality at 1-year follow-up. This suggests that lipid abnormalities in KD may be long lasting. Children with KD need careful long-term follow-up even when they do not have overt and persistent coronary artery abnormalities. It is possible that consequences of KD in childhood may impact health status of young adults several years later.

Atherosclerotic Cardiovascular Disease Beginning in Childhood

PubMed Central

2010-01-01

Although the clinical manifestations of cardiovascular disease (CVD), such as myocardial infarction, stroke, and peripheral vascular disease, appear from middle age, the process of atherosclerosis can begin early in childhood. The early stage and progression of atherosclerosis in youth are influenced by risk factors that include obesity, hypertension, dyslipidemia, and smoking, and by the presence of specific diseases, such as diabetes mellitus and Kawasaki disease (KD). The existing evidence indicates that primary prevention of atherosclerotic disease should begin in childhood. Identification of children at risk for atherosclerosis may allow early intervention to decrease the atherosclerotic process, thereby preventing or delaying CVD. This review will describe the origin and progression of atherosclerosis in childhood, and the identification and management of known risk factors for atherosclerotic CVD in children and young adults. PMID:20111646

[Changes in peripheral blood T helper 9 cells and interleukin-9 in children in the acute stage of Kawasaki disease].

PubMed

Sun, Rui-Li; Zhu, Shu-Xia; Zhang, Yan-Yan; Wu, Yi-Fei; Wang, Xing-Jian

2016-08-01

To investigate the changes in the expression levels of peripheral blood T helper 9 (Th9) cells and cytokine interleukin-9 (IL-9) in children in the acute stage of Kawasaki disease (KD) and their clinical significance. A total of 45 children in the acute stage of KD who were treated from April 2014 to July 2015 were enrolled, and the children were followed up in the recovery stage. Another 45 healthy children who underwent physical examination were enrolled as the control group. Flow cytometry was used to measure the percentage of peripheral blood Th9 cells, and ELISA was used to measure the serum level of IL-9. The children in the acute stage of KD showed a significantly higher percentage of Th9 cells and a significantly higher serum level of IL-9 compared with those in the recovery stage and the control group (P<0.05). The percentage of Th9 cells and serum level of IL-9 showed no significant differences between the children in the recovery stage and those in the control group (P>0.05). In the acute stage, the percentage of Th9 cells was positively correlated with the levels of IL-9, C-reactive protein (CRP), procalcitonin (PCT), erythrocyte sedimentation rate (ESR), platelet count (PLT), and globulin (r=0.624, 0.324, 0.402, 0.382, 0.467, and 0.386 respectively, all P<0.05), but negatively correlated with serum albumin (r=-0.306, P<0.05). The serum level of IL-9 was positively correlated with the levels of CRP, PCT, ESR, PLT, and globulin (r=0.365, 0.456, 0.403, 0.423, and 0.453 respectively, all P<0.05), but negatively correlated with serum albumin (r=-0.343, P<0.05). The children in the acute stage of KD show significant increases in the percentage of peripheral Th9 cells and serum cytokine IL-9 level, which return to normal in the recovery stage. In the acute stage of KD, the expression levels of Th9 and IL-9 are closely correlated with laboratory markers. The results suggest that Th9 cells and IL-9 play important roles in the pathogenesis and outcome of KD.

Clinical characteristics and serum N-terminal pro-brain natriuretic peptide as a diagnostic marker of Kawasaki disease in infants younger than 3 months of age.

PubMed

Bae, Hyun Kyung; Lee, Do Kyung; Kwon, Jung Hyun; Kim, Hae Soon; Sohn, Sejung; Hong, Young Mi

2014-08-01

The incidence of Kawasaki disease (KD) is rare in young infants (less than 3 months of age), who present with only a few symptoms that fulfill the clinical diagnostic criteria. The diagnosis for KD can therefore be delayed, leading to a high risk of cardiac complications. We examined the clinical characteristics and measured the serum levels of N-terminal pro-brain natriuretic peptide (NT-proBNP) levels of these patients for assessing its value in the early detection of KD. We retrospectively reviewed the data of young infants diagnosed with KD from 2004 to 2012. The control group included 20 hospitalized febrile patients. Laboratory data, including NT-proBNP were obtained for each patient in both groups. Incomplete KD was observed in 21/24 patients (87.5%). The mean fever duration on admission was 1.36±1.0 days in the KD group. Common symptoms included erythema at the site of Bacille Calmette-Guerin inoculation (70.8%), skin rash (50.0%), changes of oropharyngeal mucosa (29.1%), and cervical lymphadenopathy (20.8%). The mean number of major diagnostic criteria fulfilled was 2.8±1.4. Five KD patients (20.8%) had only one symptom matching these criteria. The incidence of coronary artery complications was 12.5%. The mean serum NT-proBNP level in the acute phase, in the KD and control groups, were 4,159±3,714 pg/mL and 957±902 pg/mL, respectively, which decreased significantly in the convalescent phase. Incomplete KD was observed in 87.5% patients. Serum NT-proBNP might be a valuable biomarker for the early detection of KD in febrile infants aged <3 months.

The effect of FcγRIIA and FcγRIIB on coronary artery lesion formation and intravenous immunoglobulin treatment responses in children with Kawasaki disease

PubMed Central

Chang, Ling-Sai; Lo, Mao-Hung; Li, Sung-Chou; Yang, Ming-Yu; Hsieh, Kai-Sheng; Kuo, Ho-Chang

2017-01-01

Previous research has found patients with the FcγRIIIB NA1 variant having increased risk of intravenous immunoglobulin (IVIG) resistance in Kawasaki disease (KD). Our previous studies revealed that elevated FcγRIIA expression correlated with the susceptibility of KD patients. We conducted this research to determine whether and how Fcγ receptors affect the susceptibility, IVIG treatment response, and coronary artery lesions (CAL) of KD patients. The activating FcγRIIA and inhibitory FcγRIIB methylation levels of seven patients with KD and four control subjects were examined using HumanMethylation27 BeadChip. We enrolled a total of 44 KD patients and 10 control subjects with fevers. We performed real-time RT-PCR to determine the FcγRIIA and FcγRIIB expression levels, as well as a luciferase assay of FcγRIIA. We found a considerable increase in methylation of both FcγRIIA and FcγRIIB in KD patients undergoing IVIG treatment. Promoter methylation of FcγRIIA inhibited reporter activity in K562 cells using luciferase assay. The FcγRIIB mRNA expression levels were not found to increase susceptibility, CAL formation, or IVIG resistance. FcγRIIA mRNA expression levels were significantly higher in IVIG-resistant patients than in those that responded to IVIG during the pre-treatment period. Furthermore, the FcγRIIA/IIB mRNA expression ratio was considerably higher in KD patients with CAL than in those without CAL. FcγRIIA and FcγRIIB both demonstrated increased methylation levels in KD patients that underwent IVIG treatment. FcγRIIA expression influenced the IVIG treatment response of KD patients. The FcγRIIA/IIB mRNA expression ratio was greater in KD patients with CAL formation. PMID:27893416

Google-driven search for big data in autoimmune geoepidemiology: analysis of 394,827 patients with systemic autoimmune diseases.

PubMed

Ramos-Casals, Manuel; Brito-Zerón, Pilar; Kostov, Belchin; Sisó-Almirall, Antoni; Bosch, Xavier; Buss, David; Trilla, Antoni; Stone, John H; Khamashta, Munther A; Shoenfeld, Yehuda

2015-08-01

Systemic autoimmune diseases (SADs) are a significant cause of morbidity and mortality worldwide, although their epidemiological profile varies significantly country by country. We explored the potential of the Google search engine to collect and merge large series (>1000 patients) of SADs reported in the Pubmed library, with the aim of obtaining a high-definition geoepidemiological picture of each disease. We collected data from 394,827 patients with SADs. Analysis showed a predominance of medical vs. administrative databases (74% vs. 26%), public health system vs. health insurance resources (88% vs. 12%) and patient-based vs. population-based designs (82% vs. 18%). The most unbalanced gender ratio was found in primary Sjögren syndrome (pSS), with nearly 10 females affected per 1 male, followed by systemic lupus erythematosus (SLE), systemic sclerosis (SSc) and antiphospholipid syndrome (APS) (ratio of nearly 5:1). Each disease predominantly affects a specific age group: children (Kawasaki disease, primary immunodeficiencies and Schonlein-Henoch disease), young people (SLE Behçet disease and sarcoidosis), middle-aged people (SSc, vasculitis and pSS) and the elderly (amyloidosis, polymyalgia rheumatica, and giant cell arteritis). We found significant differences in the geographical distribution of studies for each disease, and a higher frequency of the three SADs with available data (SLE, inflammatory myopathies and Kawasaki disease) in African-American patients. Using a "big data" approach enabled hitherto unseen connections in SADs to emerge. Copyright © 2015 Elsevier B.V. All rights reserved.

Legionnaire's disease surveillance programme (initial survey analysis).

PubMed

O'Neill, K

1990-08-01

In Australia, approximately 150 cases of Legionnaire's Disease are reported annually. Untreated, the mortality rate is estimated at 20%. Australia's largest Legionnaire's Disease epidemic broke out in Wollongong (New South Wales) back in 1987, where some 45 cases required hospitalization and 10 of these died. Local Health Authorities have been advised to conduct initial surveys of their particular municipalities to locate all known water cooling towers and evaporative condensers to establish maintenance standards on such units to overcome possible future outbreaks of this disease with significant mortality.

Imaging findings in systemic childhood diseases presenting with dermatologic manifestations.

PubMed

Fink, Adam Z; Gittler, Julia K; Nakrani, Radhika N; Alis, Jonathan; Blumfield, Einat; Levin, Terry L

Many childhood diseases often present with skin abnormalities with which radiologists are largely unfamiliar. Knowledge of associated dermatologic manifestations may aid the radiologist in confirming the diagnosis and recommending targeted imaging of affected organs. We review the imaging findings in childhood diseases associated with dermatologic manifestations. Diseases include dermatologic findings which herald underlying malignancy (Neuroblastoma, leukemia/lymphoma, Langerhans cell histiocytosis),are associated with risk of malignancy (Epidermolysis Bullosa, basal cell nevus syndrome, Cowden's syndrome, Tuberous Sclerosis),or indicate a systemic inflammatory/immune disorder (Kawasaki's disease, Henoch Schonlein Purpura, systemic lupus erythematosus, scleroderma, sarcoidosis, dermatomyositis and immune thrombocytopenic purpura). Familiarity with pertinent findings in childhood diseases presenting with dermatologic manifestations in childhood diseases aids the radiologist in confirming the diagnosis and guiding imaging workup. Copyright © 2017 Elsevier Inc. All rights reserved.

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

CFD research and systems in Kawasaki Heavy Industries and its future prospects

NASA Astrophysics Data System (ADS)

Hiraoka, Koichi

1990-09-01

KHI Computational Fluid Dynamics (CFD) system is composed of VP100 computer and 2-D and 3-D Euler and/or Navier-Stokes (NS) analysis softwares. For KHI, this system has become a very powerful aerodynamic tool together with the Kawasaki 1 m Transonic Wind Tunnel. The 2-D Euler/NS software, developed in-house, is fully automated, requires no special skill, and was successfully applied to the design of YXX high lift devices and SST supersonic inlet, etc. The 3-D Euler/NS software, developed under joint research with NAL, has an interactively operated Multi-Block type grid generator and can effectively generate grids around complex airplane shapes. Due to the main memory size limitation, 3-D analysis of relatively simple shape, such as SST wing-body, was computed in-house on VP100, otherwise, such as detailed 3-D analyses of ASUKA and HOPE, were computed on NAL VP400, which is 10 times more powerful than VP100, under KHI-NAL joint research. These analysis results have very good correlation with experimental results. However, the present CFD system is less productive than wind tunnel and has applicability limitations.

[Initial diagnosis of Parkinson's disease - neuroradiological diagnosis].

PubMed

Orimo, Satoshi

2013-01-01

Brain MRI is essential for differentiating Parkinson's disease (PD) from other parkinsonian syndromes. The purpose of performing brain MRI is not to make a diagnosis of PD but is to exclude other parkinsonian syndromes. Recently, several new MRI techniques such as voxel based morphometry, relaxometry, magnetization transfer, spectroscopy, tractography, and functional MRI have been introduced in the diagnosis of PD. Neuromelanin imaging is one of the new techniques and can be useful to make an initial diagnosis of PD. MIBG myocardial scintigraphy is a sensitive imaging tool to differentiate PD from other parkinsonian syndromes and is one of the good tools to make an initial diagnosis of PD. Brain perfusion imaging is sometimes useful to make an initial diagnosis of PD, because reduced brain perfusion area can be detected before brain MRI detects morphological changes of the brain. Dopamine transporter imaging, not available in Japan, is a sensitive tool to detect very early parkinsonism and is useful to make an initial diagnosis of PD. However, it is difficult to differentiate PD from other parkinsonian syndromes.

Aneurysmal coronary artery disease: An overview

PubMed Central

ElGuindy, Mohamed S.

Aneurysmal coronary artery disease (ACAD) comprises both coronary artery aneurysms (CAA) and coronary artery ectasia (CAE). The reported prevalence of ACAD varies widely from 0.2 to 10%, with male predominance and a predilection for the right coronary artery (RCA). Atherosclerosis is the commonest cause of ACAD in adults, while Kawasaki disease is the commonest cause in children and adolescents, as well as in the Far East. Most patients are asymptomatic, but when symptoms do exist, they are usually related to myocardial ischemia. Coronary angiography is the mainstay of diagnosis, but follow up is best achieved using noninvasive imaging that does not involve exposure to radiation. The optimal management strategy in patients with ACAD remains controversial. Medical therapy is indicated for the vast majority of patients and includes antiplatelets and/or anticoagulants. Covered stents effectively limit further expansion of the affected coronary segments. Surgical ligation, resection, and coronary artery bypass grafting are appropriate for large lesions and for associated obstructive coronary artery disease. PMID:29564347

Initial treatment of Parkinson's disease.

PubMed

Tarsy, Daniel

2006-05-01

Initial treatment of early idiopathic Parkinson's disease (PD) begins with diagnosis based on clinical evaluation supplemented by laboratory studies and brain imaging to exclude causes of secondary parkinsonism. In most cases, testing is normal and the diagnosis of PD rests on clinical criteria. In patients with mild symptoms and signs, the diagnosis of PD may not initially be apparent, and follow-up evaluation is needed to arrive at a diagnosis. Once the diagnosis is made, pharmacologic treatment may not be the first step. First, patient education is essential, especially because PD is a high-profile disease for which information and misinformation are readily available to patients and families. Counseling concerning prognosis, future symptoms, future disability, and treatment must be provided. Questions from patients concerning diet, lifestyle, and exercise are especially common at this point. The decision of when to initiate treatment is the next major consideration. Much controversy but relatively little light has been brought to bear on this issue. L-dopa was the first major antiparkinson medication to be introduced and remains the "gold standard" of treatment. Next in efficacy are the dopamine agonists (DAs). A debate has raged concerning whether initial dopaminergic treatment should be with L-dopa or DAs. Physicians have been concerned about forestalling the appearance of dyskinesias and motor fluctuations, whereas patients have incorrectly understood that L-dopa and possibly other antiparkinson drugs have a finite duration of usefulness, making it important to defer treatment for as long as possible. This has created "L-dopa phobia," which may stand in the way of useful treatment. In spite of this controversy, there is uniform agreement that the appropriate time to treat is when the patient is beginning to be disabled. This varies from patient to patient and depends on age, employment status, nature of job, level of physical activity, concern about

Phenotypic and Molecular Characterization of Enteroaggregative Escherichia coli Isolated in Kawasaki, Japan.

PubMed

Kubomura, Akiko; Misaki, Takako; Homma, Sachiko; Matsuo, Chiaki; Okabe, Nobuhiko

2017-09-25

Enteroaggregative Escherichia coli (EAEC), an enteric pathogen, causes persistent diarrhea in children, HIV-infected individuals, and travelers in economically developing countries. However, the pathogenesis of EAEC infection is not well understood. This study aimed to characterize EAEC in Japan. Between 2012 and 2014, we identified 40 EAEC strains carrying the aggR gene at the Kawasaki City Institute for Public Health, Japan. We characterized these strains using O:H-antigen typing, polymerase chain reaction (for pCVD432, astA, extended-spectrum beta-lactamase, and 4 aggregative adherence fimbriae genes), HEp-2 cell adherence, clump formation, and antimicrobial susceptibility testing. We were able to classify the 40 EAEC strains into 20 O:H types. Although specific O:H types were not correlated with HEp-2 cell aggregative adherence, all the O99:H10, O131:H27, and O176:H34 EAEC strains that were the most frequent O:H types detected in this study showed co-resistance to ampicillin, sulfamethoxazole-trimethoprim, and tetracycline. Based on results of the adhesion assay and detection of virulence-related genes, no significant difference was found between asymptomatic and symptomatic cases. Irrespective of the origin, their potential for virulence was retained. Further characterization is vital to determine whether EAEC is virulent in Japan.

New Advances in the Treatment of Neurological Diseases Using High Dose Intravenous Immunoglobulins

PubMed Central

2008-01-01

Since the incidental discovery in 1981 that intravenous immunoglobulins (IVIg) are immunomodulatory, they have been investigated in a large number of putative autoimmune diseases. This has led to licensing for idiopathic thrombocytopenic purpura, Kawasaki disease, and in neurological disorders for Guillain-Barré syndrome (GBS). Although not licensed, randomized controlled trials have also shown IVIg efficacy in other neuroimmunological diseases such as multifocal motor neuropathy (MMN), chronic inflammatory demyelinating neuropathy (CIDP), myasthenia gravis, dermatomyositis, and stiff-person syndrome. However, other indications are currently being explored including Alzheimer's disease, postpolio syndrome, and narcolepsy. There are even reports from experimental studies in stroke. The results of recently published clinical trials in both the classical neuroimmunological disorders as well as for new indications are reported and their role in clinical practice is discussed. PMID:21180569

Quality Improvement Initiatives in Inflammatory Bowel Disease.

PubMed

Berry, Sameer K; Siegel, Corey A; Melmed, Gil Y

2017-08-01

This article serves as an overview of several quality improvement initiatives in inflammatory bowel disease (IBD). IBD is associated with significant variation in care, suggesting poor quality of care. There have been several efforts to improve the quality of care for patients with IBD. Quality improvement (QI) initiatives in IBD are intended to be patient-centric, improve outcomes for individuals and populations, and reduce costs-all consistent with "the triple aim" put forth by the Institute for Healthcare Improvement (IHI). Current QI initiatives include the development of quality measure sets to standardize processes and outcomes, learning health systems to foster collaborative improvement, and patient-centered medical homes specific to patients with IBD in shared risk models of care. Some of these programs have demonstrated early success in improving patient outcomes, reducing costs, improving patient satisfaction, and facilitating patient engagement. However, further studies are needed to evaluate and compare the effects of these programs over time on clinical outcomes in order to demonstrate long-term value and sustainability.

Impact of the Alzheimer's Disease Neuroimaging Initiative, 2004 to 2014.

PubMed

Weiner, Michael W; Veitch, Dallas P; Aisen, Paul S; Beckett, Laurel A; Cairns, Nigel J; Cedarbaum, Jesse; Donohue, Michael C; Green, Robert C; Harvey, Danielle; Jack, Clifford R; Jagust, William; Morris, John C; Petersen, Ronald C; Saykin, Andrew J; Shaw, Leslie; Thompson, Paul M; Toga, Arthur W; Trojanowski, John Q

2015-07-01

The Alzheimer's Disease Neuroimaging Initiative (ADNI) was established in 2004 to facilitate the development of effective treatments for Alzheimer's disease (AD) by validating biomarkers for AD clinical trials. We searched for ADNI publications using established methods. ADNI has (1) developed standardized biomarkers for use in clinical trial subject selection and as surrogate outcome measures; (2) standardized protocols for use across multiple centers; (3) initiated worldwide ADNI; (4) inspired initiatives investigating traumatic brain injury and post-traumatic stress disorder in military populations, and depression, respectively, as an AD risk factor; (5) acted as a data-sharing model; (6) generated data used in over 600 publications, leading to the identification of novel AD risk alleles, and an understanding of the relationship between biomarkers and AD progression; and (7) inspired other public-private partnerships developing biomarkers for Parkinson's disease and multiple sclerosis. ADNI has made myriad impacts in its first decade. A competitive renewal of the project in 2015 would see the use of newly developed tau imaging ligands, and the continued development of recruitment strategies and outcome measures for clinical trials. Copyright © 2015 The Alzheimer's Association. All rights reserved.

76 FR 28437 - Disease, Disability, and Injury Prevention and Control Special Interest Project (SIP): Initial...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-05-17

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Centers for Disease Control and Prevention Disease, Disability, and Injury Prevention and Control Special Interest Project (SIP): Initial Review The meeting... Disease or Treated by Assisted Reproductive Technology, SIP11-048, Panel F,'' initial review In accordance...

Long-term effect of initiating pramipexole vs levodopa in early Parkinson disease.

PubMed

2009-05-01

To compare the long-term outcomes of subjects initially treated with pramipexole dihydrochloride with those of subjects initially treated with levodopa in the Comparison of the Agonist Pramipexole With Levodopa on Motor Complications of Parkinson's Disease (CALM-PD) trial. Up to 2 years of open extended follow-up of the CALM-PD subjects. Academic movement disorders clinics at 22 sites in the United States and Canada. Patients Patients with early Parkinson disease (N = 301) who required dopaminergic therapy to treat emerging disability were enrolled between October 1996 and August 1997, a subset of whom consented to extended follow-up until August 2003 (n = 222). Intervention Subjects were randomized to receive initial treatment with either pramipexole (n = 151) or levodopa (n = 150). Investigators were permitted to add open-label levodopa or other antiparkinsonian medications to treat ongoing or emerging disability. The primary outcome variable was the time-weighted average of self-reported disability scores in the "on" and "off" states as measured by the Schwab and England Activities of Daily Living Scale at the final visit. Secondary outcomes included the Unified Parkinson's Disease Rating Scale score, the presence and severity of dopaminergic motor complications, quality-of-life scale scores, Geriatric Depression Scale score, Epworth Sleepiness Scale score, and adverse events. After a mean (SD) follow-up of 6.0 (0.2) years, mean (SD) self-reported weighted Schwab and England Activities of Daily Living Scale scores were similar in the initial pramipexole (79.9 [16.2]) and initial levodopa (82.5 [14.6]) groups (P = .19). Dopaminergic motor complications (wearing off, on-off effects, or dyskinesias) were more common in the initial levodopa group (68.4%) than in the initial pramipexole group (50.0%) (P = .002), although disabling dyskinesias were uncommon in both groups. The mean (SD) Epworth Sleepiness Scale score was significantly higher in the initial pramipexole

Occurrence of Autoimmune Diseases Related to the Vaccine against Yellow Fever

PubMed Central

Oliveira, Ana Cristina Vanderley; Maria Henrique da Mota, Licia; dos Santos-Neto, Leopoldo Luiz; De Carvalho, Jozélio Freire; Caldas, Iramaya Rodrigues; Martins Filho, Olindo Assis; Tauil, Pedro Luis

2014-01-01

Yellow fever is an infectious disease, endemic in South America and Africa. This is a potentially serious illness, with lethality between 5 and 40% of cases. The most effective preventive vaccine is constituted by the attenuated virus strain 17D, developed in 1937. It is considered safe and effective, conferring protection in more than 90% in 10 years. Adverse effects are known as mild reactions (allergies, transaminases transient elevation, fever, headache) and severe (visceral and neurotropic disease related to vaccine). However, little is known about its potential to induce autoimmune responses. This systematic review aims to identify the occurrence of autoinflammatory diseases related to 17D vaccine administration. Six studies were identified describing 13 possible cases. The diseases were Guillain-Barré syndrome, multiple sclerosis, multiple points evanescent syndrome, acute disseminated encephalomyelitis, autoimmune hepatitis, and Kawasaki disease. The data suggest that 17D vaccination may play a role in the mechanism of loss of self-tolerance. PMID:25405025

[Initial deficits in Alzheimer's disease: 3 practical examples].

PubMed

Jódar-Vicente, M

The aim of the first studies to determine the neuropsychological features of Alzheimer's disease (AD) were based on the concept of the disease as an homogeneous entity. However, clinical observations and the most recent research studies have demonstrated that Alzheimer's disease may present several other neuropsychological deficits on its clinical onset. in the initial process of cognitive function loss, memory deficits are seen as a consequence of hippocampal degeneration; however, a great interindividual variability is observed in the appearance of other cortical deficits. In addiction, new advances in epidemiology, neurochemistry and neuropathology support the idea that AD represents a neuropsychologically heterogeneous disorder. In AD three different subgroups have been established: patients with initial deficits in visuospatial abilities, patients with a major deterioration of linguistic abilities, and a third group with altered visuospatial and linguistic abilities. The most sensitive neuropsychological tests capable of distinguish among these differences were The Boston Naming Test (BNT) and the copy of a drawing. These results have been confirmed with single photon emission computed tomography (SPECT) images, and has been observed that patients with a pattern of a elevated right-hemispheric deterioration presented also a higher right-hipofunctionality. At the same time, patients with an elevated linguistic deficit showed a higher hipofunctionality image in the left hemisphere. In this work we present three patients from a prospective study in course, who have similar background, education, gender and disease evolution, but with an onset of the illness corresponding to each of the patterns previously described All three patients were explored with an extense neuropsychological battery of tests specially chosen for this study.

Impact of the Alzheimer’s Disease Neuroimaging Initiative, 2004 to 2014

PubMed Central

Weiner, Michael W.; Veitch, Dallas P.; Aisen, Paul S.; Beckett, Laurel A.; Cairns, Nigel J.; Cedarbaum, Jesse; Donohue, Michael C.; Green, Robert C.; Harvey, Danielle; Jack, Clifford R.; Jagust, William; Morris, John C.; Petersen, Ronald C.; Saykin, Andrew J.; Shaw, Leslie; Thompson, Paul M.; Toga, Arthur W.; Trojanowski, John Q.

2015-01-01

Introduction The Alzheimer’s Disease Neuroimaging Initiative (ADNI) was established in 2004 to facilitate the development of effective treatments for Alzheimer’s disease (AD) by validating biomarkers for AD clinical trials. Methods We searched for ADNI publications using established methods. Results ADNI has (1) developed standardized biomarkers for use in clinical trial subject selection and as surrogate outcome measures; (2) standardized protocols for use across multiple centers; (3) initiated worldwide ADNI; (4) inspired initiatives investigating traumatic brain injury and post-traumatic stress disorder in military populations, and depression, respectively, as an AD risk factor; (5) acted as a data-sharing model; (6) generated data used in over 600 publications, leading to the identification of novel AD risk alleles, and an understanding of the relationship between biomarkers and AD progression; and (7) inspired other public-private partnerships developing biomarkers for Parkinson’s disease and multiple sclerosis. Discussion ADNI has made myriad impacts in its first decade. A competitive renewal of the project in 2015 would see the use of newly developed tau imaging ligands, and the continued development of recruitment strategies and outcome measures for clinical trials. PMID:26194320

Coronary heart disease mortality and hormone therapy before and after the Women's Health Initiative.

PubMed

Tuomikoski, Pauliina; Lyytinen, Heli; Korhonen, Pasi; Hoti, Fabian; Vattulainen, Pia; Gissler, Mika; Ylikorkala, Olavi; Mikkola, Tomi S

2014-11-01

To assess whether coronary heart disease mortality in Finnish hormone therapy (HT) users differed before and after 2002 when the Women's Health Initiative study was published. The risks of coronary heart disease death in HT users in relation to the age-matched background population were compared between the pre- (1995-2001) and post- (2002-2009) Women's Health Initiative eras. We used a nationwide register on HT (ie, estradiol with or without progestin) reimbursement and linked them to causes of death in 290,272 women aged 40 years or older. Exposure to HT for 1 year or less was accompanied by a 29% reduction (0.71; 0.63-0.80; three per 10,000 fewer deaths) and an exposure of 1-8 years with a 43% reduction (0.57; 0.48-0.66; three per 10,000 fewer deaths) in the risk of coronary heart disease death in the pre-Women's Health Initiative era. In the post-Women's Health Initiative era, HT use of 1 year or less was associated with an 18% reduction (0.82; 0.76-1.00; one per 10,000 fewer deaths) and an exposure of 1-8 years with a 54% reduction (0.46; 0.32-0.64; two per 10,000 fewer deaths) in coronary heart disease mortality. Discontinuation of HT was associated with an increased risk of cardiac death of 42% (1.42; 1.17-1.71; seven per 10,000 extra deaths) in the pre-Women's Health Initiative era and 31% (1.31; 0.92-1.82; two per 10,000 extra deaths) in the post-Women's Health Initiative era during the first posttreatment year. This risk increase vanished in further follow-up during both eras. Changes in HT use after the Women's Health Initiative failed to affect coronary heart disease mortality of HT users in this nationwide study.

Effects of auditory cues on gait initiation and turning in patients with Parkinson's disease.

PubMed

Gómez-González, J; Martín-Casas, P; Cano-de-la-Cuerda, R

2016-12-08

To review the available scientific evidence about the effectiveness of auditory cues during gait initiation and turning in patients with Parkinson's disease. We conducted a literature search in the following databases: Brain, PubMed, Medline, CINAHL, Scopus, Science Direct, Web of Science, Cochrane Database of Systematic Reviews, Cochrane Library Plus, CENTRAL, Trip Database, PEDro, DARE, OTseeker, and Google Scholar. We included all studies published between 2007 and 2016 and evaluating the influence of auditory cues on independent gait initiation and turning in patients with Parkinson's disease. The methodological quality of the studies was assessed with the Jadad scale. We included 13 studies, all of which had a low methodological quality (Jadad scale score≤2). In these studies, high-intensity, high-frequency auditory cues had a positive impact on gait initiation and turning. More specifically, they 1) improved spatiotemporal and kinematic parameters; 2) decreased freezing, turning duration, and falls; and 3) increased gait initiation speed, muscle activation, and gait speed and cadence in patients with Parkinson's disease. We need studies of better methodological quality to establish the Parkinson's disease stage in which auditory cues are most beneficial, as well as to determine the most effective type and frequency of the auditory cue during gait initiation and turning in patients with Parkinson's disease. Copyright © 2016 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

Reproductive Health in Men and Women With Vasculitis

ClinicalTrials.gov

2014-06-25

Giant Cell Arteritis; Takayasu's Arteritis; Polyarteritis Nodosa; Wegener's Granulomatosis; Microscopic Polyangiitis; Churg-Strauss Syndrome; Behcet's Disease; Kawasaki Disease; Henoch-schoenlein Purpura; Vasculitis, Central Nervous System; Drug-induced Necrotizing Vasculitis

78 FR 17412 - Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Initial Review

Federal Register 2010, 2011, 2012, 2013, 2014

2013-03-21

... Control of Neglected Tropical Diseases in Africa, FOA GH13-002, initial review. In accordance with Section... Neglected Tropical Diseases in Africa, FOA GH13-002, initial review.'' Contact Person for More Information...

Degree of host susceptibility in the initial disease outbreak influences subsequent epidemic spread

PubMed Central

Severns, Paul M.; Estep, Laura K.; Sackett, Kathryn E.; Mundt, Christopher C.

2014-01-01

Summary Disease epidemics typically begin as an outbreak of a relatively small, spatially explicit population of infected individuals (focus), in which disease prevalence increases and rapidly spreads into the uninfected, at-risk population. Studies of epidemic spread typically address factors influencing disease spread through the at-risk population, but the initial outbreak may strongly influence spread of the subsequent epidemic.We initiated wheat stripe rust Puccinia striiformis f. sp. tritici epidemics to assess the influence of the focus on final disease prevalence when the degree of disease susceptibility differed between the at-risk and focus populations.When the focus/at-risk plantings consisted of partially genetic resistant and susceptible cultivars, final disease prevalence was statistically indistinguishable from epidemics produced by the focus cultivar in monoculture. In these experimental epidemics, disease prevalence was not influenced by the transition into an at-risk population that differed in disease susceptibility. Instead, the focus appeared to exert a dominant influence on the subsequent epidemic.Final disease prevalence was not consistently attributable to either the focus or the at-risk population when focus/at-risk populations were planted in a factorial set-up with a mixture (~28% susceptible and 72% resistant) and susceptible individuals. In these experimental epidemics, spatial heterogeneity in disease susceptibility within the at-risk population appeared to counter the dominant influence of the focus.Cessation of spore production from the focus (through fungicide/glyphosate application) after 1.3 generations of stripe rust spread did not reduce final disease prevalence, indicating that the focus influence on disease spread is established early in the epidemic.Synthesis and applications. Our experiments indicated that outbreak conditions can be highly influential on epidemic spread, even when disease resistance in the at-risk population

Coronary aneurysms in a child: an unusual presentation of pseudovasculitis.

PubMed

Seguro, Luciana P C; Freire de Carvalho, Jozelio; Lianza, Alessandro C; Pereira, Rosa M R

2013-01-01

Abnormalities of the coronary arteries in children are rare and Kawasaki disease is the most common cause of acquired coronary disease in a paediatric population. We report a case of a female child with coronary artery aneurysms and convulsions, who was diagnosed with Kawasaki disease. Due to systemic arterial hypertension and persistence of high inflammatory markers after treatment with high dose glucocorticoid and intravenous immunoglobulin, further investigation was performed and revealed a pheochromocytoma. Surgical removal led to normalization of blood pressure and laboratory parameters. Periodic echocardiography studies revealed progressive reduction of coronary aneurysms, with complete normalisation after 8 months. This is the first case described of coronary aneurysms presenting as a pseudovasculitis syndrome associated with pheochromocytoma.

Pretibial myxedema without ophthalmopathy: an initial presentation of Graves' disease.

PubMed

Lohiya, Sheela; Lohiya, Vipin; Stahl, Elizabeth J

2013-07-01

To report a rare case of Graves' disease without ophthalmopathy presenting with pretibial myxedema (PM) as an initial presentation. We present the clinical history, physical findings, laboratory studies and biopsy data of a 62-year-old man with a history of uncontrolled type 2 diabetes (DM2) presenting with arm and leg skin lesions in the absence of other physical findings. Histopathology confirmed PM. Graves' disease and its association with PM without Graves' ophthalmopathy and the pertinent literature are reviewed. A 60-year-old man with a history of uncontrolled DM2 presented for glycemic management. He described symptoms of anxiety, insomnia and fatigue for the last 5 to 6 months. He described diffuse chest pain, occasionally associated with palpitations, and a 50-pound weight loss. He also complained of severe itching and burning of his arms and legs for the past several months. Subsequent thyroid studies revealed hyperthyroidism suggestive of Graves' disease. In the interim, he was hospitalized for atrial flutter and was cardioverted. After being started on methimazole, his symptoms abated. His skin lesions were biopsied, and the leg biopsy was consistent with PM. He however had no lid lag or proptosis characteristic of Graves' disease. He subsequently underwent radioiodine ablation. His hyperglycemia was better control led after treatment of his hyperthyroidism. PM is an autoimmune manifestation of Graves' disease. Almost all cases of thyroid dermopathy are associated with relatively severe ophthalmopathy. Usually ophthalmopathy appears first and dermopathy much later. However, this case represents a rare initial presentation of Graves' disease with PM without ophthalmologic symptoms or findings. Hyperthyroidism is typically associated with worsening glycemic control and increased insulin requirements. In patients with diabetes having hyperthyroidism, deterioration in glycemic control should be anticipated and treatment should be adjusted accordingly

Tobacco-related disease burden and preventive initiatives in China. Global health and the chronic diseases: perspective, policy and practice.

PubMed

Niu, Bolin

2011-06-01

The burden of chronic diseases in global health is a surging area of research. The Global Health Initiative at the National Heart, Lung, and Blood Institute brings together investigators from developing countries with those from the developed world to study these diseases. In China, approximately 83 percent of all deaths in 2000 were attributed to chronic illnesses, which are the research focuses of the Chinese center of the Global Health Initiative. Tobacco use as well as passive smoking are modifiable risk factors in a large number of such chronic conditions. The prevalence of smoking in China is extensive and has inseparable ties to the economy, with tobacco taxes making up a large portion of government revenue in poorer provinces. Methods of smoking prevention have been piloted in some Chinese schools, which have mitigated the increase in smoking rate but have not resulted in a primary preventive effect. Efforts by the Yale Global Health Initiative and the Yale-China Association are bringing researchers together to address chronic disease in China as Yale School of Medicine enters its 200th year.

The dynamics of Alzheimer's disease biomarkers in the Alzheimer's Disease Neuroimaging Initiative cohort.

PubMed

Caroli, A; Frisoni, G B

2010-08-01

The aim of this study was to investigate the dynamics of four of the most validated biomarkers for Alzheimer's disease (AD), cerebro-spinal fluid (CSF) Abeta 1-42, tau, hippocampal volume, and FDG-PET, in patients at different stage of AD. Two hundred twenty-nine cognitively healthy subjects, 154 mild cognitive impairment (MCI) patients converted to AD, and 193 (95 early and 98 late) AD patients were selected from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. For each biomarker, individual values were Z-transformed and plotted against ADAS-cog scores, and sigmoid and linear fits were compared. For most biomarkers the sigmoid model fitted data significantly better than the linear model. Abeta 1-42 time course followed a steep curve, stabilizing early in the disease course. CSF tau and hippocampal volume changed later showing similar monotonous trends, reflecting disease progression. Hippocampal loss trend was steeper and occurred earlier in time in APOE epsilon4 carriers than in non-carriers. FDG-PET started changing early in time and likely followed a linear decline. In conclusion, this study provides the first evidence in favor of the dynamic biomarker model which has recently been proposed. 2010 Elsevier Inc. All rights reserved.

Mitral stenosis

MedlinePlus

... KA, Gerwitz M, et al. Prevention of infective endocarditis: guidelines from the American Heart Association: a guideline from the American Heart Association Rheumatic Fever, Endocarditis, and Kawasaki Disease Committee, Council on Cardiovascular Disease ...

Staphylococcal superantigens in colonization and disease

PubMed Central

Xu, Stacey X.; McCormick, John K.

2012-01-01

Superantigens (SAgs) are a family of potent immunostimulatory exotoxins known to be produced by only a few bacterial pathogens, including Staphylococcus aureus. More than 20 distinct SAgs have been characterized from different S. aureus strains and at least 80% of clinical strains harbor at least one SAg gene, although most strains encode many. SAgs have been classically associated with food poisoning and toxic shock syndrome (TSS), for which these toxins are the causative agent. TSS is a potentially fatal disease whereby SAg-mediated activation of T cells results in overproduction of cytokines and results in systemic inflammation and shock. Numerous studies have also shown a possible role for SAgs in other diseases such as Kawasaki disease (KD), atopic dermatitis (AD), and chronic rhinosinusitis (CRS). There is also now a rich understanding of the mechanisms of action of SAgs, as well as their structures and function. However, we have yet to discover what purpose SAgs play in the life cycle of S. aureus, and why such a wide array of these toxins exists. This review will focus on recent developments within the SAg field in terms of the molecular biology of these toxins and their role in both colonization and disease. PMID:22919643

Age, Predisposing Diseases, and Ultrasonographic Findings in Determining Clinical Outcome of Acute Acalculous Inflammatory Gallbladder Diseases in Children

PubMed Central

2016-01-01

We evaluated clinical factors such as age, gender, predisposing diseases and ultrasonographic findings that determine clinical outcome of acute acalculous inflammatory gallbladder diseases in children. The patients were divided into the four age groups. From March 2004 through February 2014, clinical data from 131 children diagnosed as acute acalculous inflammatory gallbladder disease by ultrasonography were retrospectively reviewed. Systemic infectious diseases were the most common etiology of acute inflammatory gallbladder disease in children and were identified in 50 patients (38.2%). Kawasaki disease was the most common predisposing disease (28 patients, 21.4%). The incidence was highest in infancy and lowest in adolescence. The age groups were associated with different predisposing diseases; noninfectious systemic disease was the most common etiology in infancy and early childhood, whereas systemic infectious disease was the most common in middle childhood and adolescence (P = 0.001). Gallbladder wall thickening was more commonly found in malignancy (100%) and systemic infection (94.0%) (P = 0.002), whereas gallbladder distension was more frequent in noninfectious systemic diseases (60%) (P = 0.000). Ascites seen on ultrasonography was associated with a worse clinical course compared with no ascites (77.9% vs. 37.7%, P = 0.030), and the duration of hospitalization was longer in patients with ascites (11.6 ± 10.7 vs. 8.0 ± 6.6 days, P = 0.020). In conclusion, consideration of age and predisposing disease in addition to ultrasonographic gallbladder findings in children suspected of acute acalculous inflammatory gallbladder disease might result in better outcomes. PMID:27550491

76 FR 28437 - Disease, Disability, and Injury Prevention and Control Special Interest Project (SIP): Initial...

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Epidemiology of Tsutsugamushi disease in relation to the serotypes of Rickettsia tsutsugamushi isolated from patients, field mice, and unfed chiggers on the eastern slope of Mount Fuji, Shizuoka Prefecture, Japan.

PubMed Central

Kawamori, F; Akiyama, M; Sugieda, M; Kanda, T; Akahane, S; Uchikawa, K; Yamada, Y; Kumada, N; Furuya, Y; Yoshida, Y

1992-01-01

A total of 59 strains of Rickettsia tsutsugamushi were isolated from patients (24 isolates), Apodemus speciosus mice (30 isolates), and unfed larvae of Leptotrombidium scutellare (2 isolates) and Leptotrombidium pallidum (3 isolates) in the Gotenba-Oyama District, Shizuoka Prefecture, Japan. All these isolates were classified into the three serotypes Karp, Kawasaki, and Kuroki based on reactivity with strain-specific monoclonal antibodies. Kawasaki- and Karp-type rickettsiae were isolated from L. scutellare and L. pallidum, respectively, and the geographic distribution of patients and rodents infected with these two types of rickettsiae coincided with the areas densely populated by the respective chiggers. From these results, we conclude that Kawasaki-type rickettsiae are transmitted by L. scutellare and Karp-type ones are transmitted by L. pallidum. Kawasaki-type rickettsial infections were prevalent in early autumn, and Karp-type infections showed a peak of occurrence in the late autumn, reflecting the seasonal fluctuations of L. scutellare and L. pallidum. Isolates of Kuroki-type rickettsiae were obtained only from four patients in October and November, and the relationship between this type of rickettsia and its vector species could not be fully defined. PMID:1452653

75 FR 9902 - Agency Forms Undergoing Paperwork Reduction Act Review

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2010-03-04

...), Cyclospora, Dengue, Hantavirus, Kawasaki Syndrome, Legionellosis, Lyme disease, Malaria, Plague, Q Fever, Reye Syndrome, Tickborne Rickettsial Disease, Trichinosis, Tularemia, Typhoid Fever, and Viral... response respondents respondent (in hours) Epidemiologist Tyhphoid fever 55 6 20/60 Viral hepatitis...

77 FR 30292 - Disease, Disability, and Injury Prevention and Control Special Interest Project (SIP): Initial...

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... DEPARTMENT OF HEALTH AND HUMAN SERVICES Centers for Disease Control and Prevention Disease, Disability, and Injury Prevention and Control Special Interest Project (SIP): Initial Review The meeting...)(2) of the Federal Advisory Committee Act (Pub. L. 92-463), the Centers for Disease Control and...

Echocardiography Criteria for Structural Heart Disease in Patients With End-Stage Renal Disease Initiating Hemodialysis.

PubMed

Hickson, LaTonya J; Negrotto, Sara M; Onuigbo, Macaulay; Scott, Christopher G; Rule, Andrew D; Norby, Suzanne M; Albright, Robert C; Casey, Edward T; Dillon, John J; Pellikka, Patricia A; Pislaru, Sorin V; Best, Patricia J M; Villarraga, Hector R; Lin, Grace; Williams, Amy W; Nkomo, Vuyisile T

2016-03-15

Cardiovascular disease among hemodialysis (HD) patients is linked to poor outcomes. The Acute Dialysis Quality Initiative Workgroup proposed echocardiographic (ECHO) criteria for structural heart disease (SHD) in dialysis patients. The association of SHD with important patient outcomes is not well defined. This study sought to determine prevalence of ECHO-determined SHD and its association with survival among incident HD patients. We analyzed patients who began chronic HD from 2001 to 2013 who underwent ECHO ≤1 month prior to or ≤3 months following initiation of HD (n = 654). Mean patient age was 66 ± 16 years, and 60% of patients were male. ECHO findings that met 1 or more and ≥3 of the new criteria were discovered in 87% and 54% of patients, respectively. Over a median of 2.4 years, 415 patients died: 108 (26%) died within 6 months. Five-year mortality was 62%. Age- and sex-adjusted structural heart disease variables associated with death were left ventricular ejection fraction (LVEF) ≤45% (hazard ratio [HR]: 1.48; confidence interval [CI]: 1.20 to 1.83) and right ventricular (RV) systolic dysfunction (HR: 1.68; CI: 1.35 to 2.07). An additive of higher death risk included LVEF ≤45% and RV systolic dysfunction rather than neither (HR: 2.04; CI: 1.57 to 2.67; p = 0.53 for test for interaction). Following adjustment for age, sex, race, diabetic kidney disease, and dialysis access, RV dysfunction was independently associated with death (HR: 1.66; CI 1.34 to 2.06; p < 0.001). SHD was common in our HD study population, and RV systolic dysfunction independently predicted mortality. Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Emotional state affects gait initiation in individuals with Parkinson’s disease

PubMed Central

Hass, Chris J.; Bowers, Dawn; Janelle, Christopher M.

2013-01-01

The purpose of the present study was to determine the impact of manipulating emotional state on gait initiation in persons with Parkinson’s disease (PD) and healthy older adults. Following the presentation of pictures that are known to elicit specific emotional responses, participants initiated gait and continued to walk for several steps at their normal pace. Reaction time, the displacement and velocity of the center of pressure (COP) trajectory during the preparatory postural adjustments, and length and velocity of the first two steps were measured. Analysis of the gait initiation measures revealed that exposure to (1) threatening pictures, relative to all other pictures, speeded the initiation of gait for PD patients and healthy older adults; (2) approach-oriented emotional pictures (erotic and happy people), relative to withdrawal-oriented pictures, facilitated the anticipatory postural adjustments of gait initiation for PD patients and healthy older adults, as evidenced by greater displacement and velocity of the COP movement; and (3) emotional pictures modulated gait initiation parameters in PD patients to the same degree as in healthy older adults. Collectively, these findings hold significant implications for understanding the circuitry underlying the manner by which emotions modulate movement and for the development of emotion-based interventions designed to maximize improvements in gait initiation for individuals with PD. PMID:22194236

Tuberculosis Control - SD Dept. of Health

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Salmonellosis Scabies SARS - Severe Acute Respiratory Syndrome Shigellosis Shingles Silicosis Sinusitis - NIH Communicable Diseases Communicable Disease Links Disease Fact Sheets Acute Pesticide Poisoning AIDS/HIV Algal Hepatitis C Herpes Gladiatorum Herpes II Histoplasmosis Infectious Mononucleosis Influenza Kawasaki Syndrome

Initiating an undiagnosed diseases program in the Western Australian public health system.

PubMed

Baynam, Gareth; Broley, Stephanie; Bauskis, Alicia; Pachter, Nicholas; McKenzie, Fiona; Townshend, Sharron; Slee, Jennie; Kiraly-Borri, Cathy; Vasudevan, Anand; Hawkins, Anne; Schofield, Lyn; Helmholz, Petra; Palmer, Richard; Kung, Stefanie; Walker, Caroline E; Molster, Caron; Lewis, Barry; Mina, Kym; Beilby, John; Pathak, Gargi; Poulton, Cathryn; Groza, Tudor; Zankl, Andreas; Roscioli, Tony; Dinger, Marcel E; Mattick, John S; Gahl, William; Groft, Stephen; Tifft, Cynthia; Taruscio, Domenica; Lasko, Paul; Kosaki, Kenjiro; Wilhelm, Helene; Melegh, Bela; Carapetis, Jonathan; Jana, Sayanta; Chaney, Gervase; Johns, Allison; Owen, Peter Wynn; Daly, Frank; Weeramanthri, Tarun; Dawkins, Hugh; Goldblatt, Jack

2017-05-03

New approaches are required to address the needs of complex undiagnosed diseases patients. These approaches include clinical genomic diagnostic pipelines, utilizing intra- and multi-disciplinary platforms, as well as specialty-specific genomic clinics. Both are advancing diagnostic rates. However, complementary cross-disciplinary approaches are also critical to address those patients with multisystem disorders who traverse the bounds of multiple specialties and remain undiagnosed despite existing intra-specialty and genomic-focused approaches. The diagnostic possibilities of undiagnosed diseases include genetic and non-genetic conditions. The focus on genetic diseases addresses some of these disorders, however a cross-disciplinary approach is needed that also simultaneously addresses other disorder types. Herein, we describe the initiation and summary outcomes of a public health system approach for complex undiagnosed patients - the Undiagnosed Diseases Program-Western Australia (UDP-WA). Briefly the UDP-WA is: i) one of a complementary suite of approaches that is being delivered within health service, and with community engagement, to address the needs of those with severe undiagnosed diseases; ii) delivered within a public health system to support equitable access to health care, including for those from remote and regional areas; iii) providing diagnoses and improved patient care; iv) delivering a platform for in-service and real time genomic and phenomic education for clinicians that traverses a diverse range of specialties; v) retaining and recapturing clinical expertise; vi) supporting the education of junior and more senior medical staff; vii) designed to integrate with clinical translational research; and viii) is supporting greater connectedness for patients, families and medical staff. The UDP-WA has been initiated in the public health system to complement existing clinical genomic approaches; it has been targeted to those with a specific diagnostic need

78 FR 60878 - Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Initial Review

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2013-10-02

... announced below concerns Health Promotion and Disease Prevention Research Centers, Funding Opportunity... DEPARTMENT OF HEALTH AND HUMAN SERVICES Centers for Disease Control and Prevention Disease... Be Discussed: The meeting will include the initial review, discussion, and evaluation of ``Health...

Polio Eradication Initiative: Contribution to improved communicable diseases surveillance in WHO African region.

PubMed

Mwengee, William; Okeibunor, Joseph; Poy, Alain; Shaba, Keith; Mbulu Kinuani, Leon; Minkoulou, Etienne; Yahaya, Ali; Gaturuku, Peter; Landoh, Dadja Essoya; Nsubuga, Peter; Salla, Mbaye; Mihigo, Richard; Mkanda, Pascal

2016-10-10

Since the launch of the Global Polio Eradication Initiative (GPEI) in 1988, there has been a tremendous progress in the reduction of cases of poliomyelitis. The world is on the verge of achieving global polio eradication and in May 2013, the 66th World Health Assembly endorsed the Polio Eradication and Endgame Strategic Plan (PEESP) 2013-2018. The plan provides a timeline for the completion of the GPEI by eliminating all paralytic polio due to both wild and vaccine-related polioviruses. We reviewed how GPEI supported communicable disease surveillance in seven of the eight countries that were documented as part of World Health Organization African Region best practices documentation. Data from WHO African region was also reviewed to analyze the performance of measles cases based surveillance. All 7 countries (100%) which responded had integrated communicable diseases surveillance core functions with AFP surveillance. The difference is on the number of diseases included based on epidemiology of diseases in a particular country. The results showed that the polio eradication infrastructure has supported and improved the implementation of surveillance of other priority communicable diseases under integrated diseases surveillance and response strategy. As we approach polio eradication, polio-eradication initiative staff, financial resources, and infrastructure can be used as one strategy to build IDSR in Africa. As we are now focusing on measles and rubella elimination by the year 2020, other disease-specific programs having similar goals of eradicating and eliminating diseases like malaria, might consider investing in general infectious disease surveillance following the polio example. Copyright © 2016 The Author(s). Published by Elsevier Ltd.. All rights reserved.

HCV Treatment Initiation in Patients with Chronic Kidney Disease: Results from ERCHIVES

PubMed Central

Butt, Adeel; Ren, Yanjie; Puenpatom, Amy; Arduino, Jean Marie; Kumar, Ritesh; Abou-Samra, Abdul-Badi

2017-01-01

Abstract Background Newer directing antiviral agents against HCV (DAAs) are safe and efficacious in persons with chronic kidney disease (CKD). Whether availability of these newer DAAs has resulted in more persons with CKD initiating HCV treatment remains unknown. Methods We identified HCV+ persons in ERCHIVES. We excluded HIV+ and HBsAg+ and those with missing HCV RNA and eGFR data. We determined the CKD stage according to National Kidney Foundation criteria. We determined the number of persons initiated on any of the approved DAA-regimen (defined as >14 days of DAA prescription). Logistic regression analyses was used to determine factors associated with treatment initiation. Results Among 76,513 evaluable persons, 21.1% initiated DAA treatment. Initiation rates differed significantly by CKD stage: 21.1% (15,136/68,469) for eGFR>90mL/minute/1.73m2 and CKD stage-2; 14.0% 9853/6,086) for CKD stage 3; and 7.6% (148/1,958) for CKD stage-4/5. Those with CKD stage-3 were 35% less likely and those with CKD stage-4/5 were 65% less likely to initiate treatment with a DAA compared with those with baseline eGFR>90mL/minute/1.73m2. Those with Body Mass Index (BMI)>30 were more likely to initiate treatment (OR 1.24, 95% CI 1.19,1.29). Treatment initiation was less likely in HCV genotype 2 or 3 and those with diabetes (OR 0.82, 95% CI 0.78,0.86), cardiovascular disease (OR 0.73, 95% CI 0.68,0.78), alcohol abuse or dependence (OR 0.75, 95% CI 0.72,0.78) or cirrhosis (OR 0.85, 95% CI 0.80,0.89) at baseline. Conclusion Persons with more advanced CKD are less likely to receive treatment for HCV. Strategies are needed to improve treatment rates in the HCV/CKD population. Disclosures A. Butt, Merck: Investigator, Grant recipient. A. Puenpatom, Merck: Employee, Salary. J. M. Arduino, Merck: Employee, Salary. R. Kumar, Merck: Employee, Salary

77 FR 74017 - Proposed Data Collections Submitted for Public Comment and Recommendations

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2012-12-12

...), Cyclosporiasis, Dengue, Hantavirus, Kawasaki Syndrome, Legionellosis, Lyme disease, Malaria, Plague, Q Fever, Reye Syndrome, Tickborne Rickettsial Disease, Trichinosis, Tularemia, Typhoid Fever, and Viral... 8 Tularemia Epidemiologist.. 55 2 20/60 37 Typhoid Fever Epidemiologist.. 55 6 20/60 110 Viral...

Loss of executive function after dialysis initiation in adults with chronic kidney disease.

PubMed

Kurella Tamura, Manjula; Vittinghoff, Eric; Hsu, Chi-Yuan; Tam, Karman; Seliger, Stephen L; Sozio, Stephen; Fischer, Michael; Chen, Jing; Lustigova, Eva; Strauss, Louise; Deo, Rajat; Go, Alan S; Yaffe, Kristine

2017-04-01

The association of dialysis initiation with changes in cognitive function among patients with advanced chronic kidney disease is poorly described. To better define this, we enrolled participants with advanced chronic kidney disease from the Chronic Renal Insufficiency Cohort in a prospective study of cognitive function. Eligible participants had a glomerular filtration rate of 20 ml/min/1.73m 2 or less, or dialysis initiation within the past two years. We evaluated cognitive function by a validated telephone battery at regular intervals over two years and analyzed test scores as z scores. Of 212 participants, 123 did not transition to dialysis during follow-up, 37 transitioned to dialysis after baseline, and 52 transitioned to dialysis prior to baseline. In adjusted analyses, the transition to dialysis was associated with a significant loss of executive function, but no significant changes in global cognition or memory. The estimated net difference in cognitive z scores at two years for participants who transitioned to dialysis during follow-up compared to participants who did not transition to dialysis was -0.01 (95% confidence interval -0.13, 0.11) for global cognition, -0.24 (-0.51, 0.03) for memory, and -0.33 (-0.60, -0.07) for executive function. Thus, among adults with advanced chronic kidney disease, dialysis initiation was associated with loss of executive function with no change in other aspects of cognition. Larger studies are needed to evaluate cognition during dialysis initiation. Published by Elsevier Inc.

Chronic granulomatous otitis externa as an initial presentation of cutaneous Crohn disease.

PubMed

Raynor, Eileen M

2014-08-01

In the limited number of Crohn disease cases involving the head and neck, there is a predilection for mucosal surfaces and rare reports of involvement in the postauricular region. To our knowledge, in all previously reported cases involving the head and neck, the patients had a known diagnosis of Crohn disease. This case describes a 10-year-old boy with a history of psoriasis and psoriasiform dermatitis who presented with bilateral chronic granulomatous otitis externa, obliteration of the external auditory canal, and fissuring, resulting in separation of the lobule from the preauricular skin. Pathologic examination results were consistent with granulomatous dermatitis concerning for cutaneous Crohn disease, and a subsequent gastroenterologic workup confirmed the diagnosis of Crohn disease. This is a report of chronic granulomatous otitis as the initial presentation of cutaneous Crohn disease in a child.

78 FR 9926 - Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Initial Review

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2013-02-12

... announced below concerns Prevalence and Incidence of Inflammatory Bowel Disease, FOA DP 13-001, initial... evaluation of applications received in response to ``Prevalence and Incidence of Inflammatory Bowel Disease...

Drugs for Neglected Diseases initiative model of drug development for neglected diseases: current status and future challenges.

PubMed

Ioset, Jean-Robert; Chang, Shing

2011-09-01

The Drugs for Neglected Diseases initiative (DNDi) is a patients' needs-driven organization committed to the development of new treatments for neglected diseases. Created in 2003, DNDi has delivered four improved treatments for malaria, sleeping sickness and visceral leishmaniasis. A main DNDi challenge is to build a solid R&D portfolio for neglected diseases and to deliver preclinical candidates in a timely manner using an original model based on partnership. To address this challenge DNDi has remodeled its discovery activities from a project-based academic-bound network to a fully integrated process-oriented platform in close collaboration with pharmaceutical companies. This discovery platform relies on dedicated screening capacity and lead-optimization consortia supported by a pragmatic, structured and pharmaceutical-focused compound sourcing strategy.

Cardiovascular Conditions of Childhood

MedlinePlus

... Learn the symptoms, diagnosis and treatment for Kawasaki disease. Congenital Heart Defects If your child is born with ... and read personal stories of young stroke survivors. Congenital Heart Defects ... about children and heart disease. Login or Sign Up to save and share ...

The Spanish biology/disease initiative within the human proteome project: Application to rheumatic diseases.

PubMed

Ruiz-Romero, Cristina; Calamia, Valentina; Albar, Juan Pablo; Casal, José Ignacio; Corrales, Fernando J; Fernández-Puente, Patricia; Gil, Concha; Mateos, Jesús; Vivanco, Fernando; Blanco, Francisco J

2015-09-08

The Spanish Chromosome 16 consortium is integrated in the global initiative Human Proteome Project, which aims to develop an entire map of the proteins encoded following a gene-centric strategy (C-HPP) in order to make progress in the understanding of human biology in health and disease (B/D-HPP). Chromosome 16 contains many genes encoding proteins involved in the development of a broad range of diseases, which have a significant impact on the health care system. The Spanish HPP consortium has developed a B/D platform with five programs focused on selected medical areas: cancer, obesity, cardiovascular, infectious and rheumatic diseases. Each of these areas has a clinical leader associated to a proteomic investigator with the responsibility to get a comprehensive understanding of the proteins encoded by Chromosome 16 genes. Proteomics strategies have enabled great advances in the area of rheumatic diseases, particularly in osteoarthritis, with studies performed on joint cells, tissues and fluids. In this manuscript we describe how the Spanish HPP-16 consortium has developed a B/D platform with five programs focused on selected medical areas: cancer, obesity, cardiovascular, infectious and rheumatic diseases. Each of these areas has a clinical leader associated to a proteomic investigator with the responsibility to get a comprehensive understanding of the proteins encoded by Chromosome 16 genes. We show how the Proteomic strategy has enabled great advances in the area of rheumatic diseases, particularly in osteoarthritis, with studies performed on joint cells, tissues and fluids. This article is part of a Special Issue entitled: HUPO 2014. Copyright © 2015 Elsevier B.V. All rights reserved.

Building chronic disease management capacity in General Practice: The South Australian GP Plus Practice Nurse Initiative.

PubMed

Fuller, Jeffrey; Koehne, Kristy; Verrall, Claire C; Szabo, Natalie; Bollen, Chris; Parker, Sharon

2015-01-01

This paper draws on the implementation experience of the South Australian GP Plus Practice Nurse Initiative in order to establish what is needed to support the development of the chronic disease management role of practice nurses. The Initiative was delivered between 2007 and 2010 to recruit, train and place 157 nurses across 147 General Practices in Adelaide. The purpose was to improve chronic disease management in General Practice, by equipping nurses to work as practice nurses who would coordinate care and establish chronic disease management systems. Secondary analysis of qualitative data contained in the Initiative evaluation report, specifically drawing on quarterly project records and four focus groups conducted with practice nurses, practice nurse coordinators and practice nurse mentors. As evidenced by the need to increase the amount of support provided during the implementation of the Initiative, nurses new to General Practice faced challenges in their new role. Nurses described a big learning curve as they dealt with role transition to a new work environment and learning a range of new skills while developing chronic disease management systems. Informants valued the skills development and support offered by the Initiative, however the ongoing difficulties in implementing the role suggested that change is also needed at the level of the Practice. While just over a half of the placement positions were retained, practice nurses expressed concern with having to negotiate the conditions of their employment. In order to advance the role of practice nurses as managers of chronic disease support is needed at two levels. At one level support is needed to assist practice nurses to build their own skills. At the level of the Practice, and in the wider health workforce system, support is also needed to ensure that Practices are organisationally ready to include the practice nurse within the practice team.

Replication Validity of Initial Association Studies: A Comparison between Psychiatry, Neurology and Four Somatic Diseases.

PubMed

Dumas-Mallet, Estelle; Button, Katherine; Boraud, Thomas; Munafo, Marcus; Gonon, François

2016-01-01

There are growing concerns about effect size inflation and replication validity of association studies, but few observational investigations have explored the extent of these problems. Using meta-analyses to measure the reliability of initial studies and explore whether this varies across biomedical domains and study types (cognitive/behavioral, brain imaging, genetic and "others"). We analyzed 663 meta-analyses describing associations between markers or risk factors and 12 pathologies within three biomedical domains (psychiatry, neurology and four somatic diseases). We collected the effect size, sample size, publication year and Impact Factor of initial studies, largest studies (i.e., with the largest sample size) and the corresponding meta-analyses. Initial studies were considered as replicated if they were in nominal agreement with meta-analyses and if their effect size inflation was below 100%. Nominal agreement between initial studies and meta-analyses regarding the presence of a significant effect was not better than chance in psychiatry, whereas it was somewhat better in neurology and somatic diseases. Whereas effect sizes reported by largest studies and meta-analyses were similar, most of those reported by initial studies were inflated. Among the 256 initial studies reporting a significant effect (p<0.05) and paired with significant meta-analyses, 97 effect sizes were inflated by more than 100%. Nominal agreement and effect size inflation varied with the biomedical domain and study type. Indeed, the replication rate of initial studies reporting a significant effect ranged from 6.3% for genetic studies in psychiatry to 86.4% for cognitive/behavioral studies. Comparison between eight subgroups shows that replication rate decreases with sample size and "true" effect size. We observed no evidence of association between replication rate and publication year or Impact Factor. The differences in reliability between biological psychiatry, neurology and somatic

Scrub typhus caused by Orientia tsutsugamushi Kawasaki-related genotypes in Shandong Province, northern China.

PubMed

Zhang, Luyan; Bi, Zhenwang; Kou, Zengqiang; Yang, Huili; Zhang, Aihua; Zhang, Shoufeng; Meng, Xiangpeng; Zheng, Li; Zhang, Meng; Yang, Hui; Zhao, Zhongtang

2015-03-01

Orientia tsutsugamushi, the causative agent of scrub typhus, is an obligate intracellular bacterium and characterized by dramatic genetic diversity. To elucidate the genotypes of O. tsutsugamushi populating in patients in Shandong Province, a new epidemic zone in China, we sequenced partial of the 56-kDa type-specific antigen gene (TSA) and identified the genotypes of 43 O. tsutsugamushi samples from human patients confirmed with scrub typhus from 2010 to 2013. All of the 43 sequences are in the same clade, 39 of them are in one branch and the other four sequences, nominated as SH1002, SH1306, SH1309, and SH1307 are in four separate branches. To clarify the clinical characterizations caused by Kawasaki-related genotypes, we studied the clinical profiles of these 43 scrub typhus patients. Most patients (88.1%) were farmers lived in rural areas. They presented with fever (100.0%), headache (79.1%), dizziness (32.6%), generalized myalgia (48.8%), fatigue (53.5%), anorexia (53.5%), facial flushing (23.3%), conjunctival congestion (11.6%), skin rashes (58.1%) and lymphadenopathy (23.3%). Eschar (97.7%) was quite common in patients, which provided doctors with a luminous clue for diagnosis of scrub typhus. Thrombocytopenia was seen in 23.1% of patients, and three patients (7.0%) had bronchopneumonia. There was no death report in Shandong Province during the study period. The present study provides beneficial data for clinical, serological, and molecular diagnosis of scrub typhus infections, and also provides foundations for subsequent studies. Copyright © 2015 Elsevier B.V. All rights reserved.

Alzheimer’s Disease Neuroimaging Initiative biomarkers as quantitative phenotypes: Genetics core aims, progress, and plans

PubMed Central

Saykin, Andrew J.; Shen, Li; Foroud, Tatiana M.; Potkin, Steven G.; Swaminathan, Shanker; Kim, Sungeun; Risacher, Shannon L.; Nho, Kwangsik; Huentelman, Matthew J.; Craig, David W.; Thompson, Paul M.; Stein, Jason L.; Moore, Jason H.; Farrer, Lindsay A.; Green, Robert C.; Bertram, Lars; Jack, Clifford R.; Weiner, Michael W.

2010-01-01

The role of the Alzheimer’s Disease Neuroimaging Initiative Genetics Core is to facilitate the investigation of genetic influences on disease onset and trajectory as reflected in structural, functional, and molecular imaging changes; fluid biomarkers; and cognitive status. Major goals include (1) blood sample processing, genotyping, and dissemination, (2) genome-wide association studies (GWAS) of longitudinal phenotypic data, and (3) providing a central resource, point of contact and planning group for genetics within Alzheimer’s Disease Neuroimaging Initiative. Genome-wide array data have been publicly released and updated, and several neuroimaging GWAS have recently been reported examining baseline magnetic resonance imaging measures as quantitative phenotypes. Other preliminary investigations include copy number variation in mild cognitive impairment and Alzheimer’s disease and GWAS of baseline cerebrospinal fluid biomarkers and longitudinal changes on magnetic resonance imaging. Blood collection for RNA studies is a new direction. Genetic studies of longitudinal phenotypes hold promise for elucidating disease mechanisms and risk, development of therapeutic strategies, and refining selection criteria for clinical trials. PMID:20451875

Identifying patterns of immune-related disease: use in disease prevention and management.

PubMed

Dietert, Rodney R; Zelikoff, Judith T

2010-05-01

Childhood susceptibility to diseases linked with immune dysfunction affects over a quarter of the pediatric population in some countries. While this alone is a significant health issue, the actual impact of immune-related diseases extends over a lifetime and involves additional secondary conditions. Some comorbidities are well known (e.g., allergic rhinitis and asthma). However, no systematic approach has been used to identify life-long patterns of immune-based disease where the primary condition arises in childhood. Such information is useful for both disease prevention and treatment approaches. Recent primary research papers as well as review articles were obtained from PubMed, Chem Abstracts, Biosis and from the personal files of the authors. Search words used were: the diseases and conditions shown Figs. 1 and 2 in conjunction with comorbid, comorbidities, pediatric, childhood, adult, immune, immune dysfunction, allergy, autoimmune, inflammatory, infectious, health risks, environment, risk factors. Childhood diseases such as asthma, type-1 diabetes, inflammatory bowel disease, respiratory infections /rhinitis, recurrent otitis media, pediatric celiac, juvenile arthritis and Kawasaki disease are examples of significant childhood health problems where immune dysfunction plays a significant role. Each of these pediatric diseases is associated with increased risk of several secondary conditions, many of which appear only later in life. To illustrate, four prototypes of immune-related disease patterns (i.e., allergy, autoimmunity, inflammation and infectious disease) are shown as tools for: 1) enhanced disease prevention; 2) improved management of immune-based pediatric diseases; and 3) better recognition of underlying pediatric immune dysfunction. Identification of immune-related disease patterns beginning in childhood provides the framework for examining the underlying immune dysfunctions that can contribute to additional diseases in later life. Many pediatric

[Challenge and strategy of prevention and control of important parasitic diseases under the Belt and Road Initiative].

PubMed

Chun-Li, Cao; Jia-Gang, Guo

2018-04-17

China was once a country with the heaviest burden of parasitic diseases. Under the leadership of the Communist Party and national authority, after more than 60 years' efforts of prevention and control, the remarkable results have been achieved in China. However, affected by the social and economic development and environmental changes, the prevention and control of parasitic diseases, especially imported parasitic diseases, are facing new challenges, and the parasitic diseases, such as malaria, schistosomiasis, leishmaniasis, filariasis and trypanosomiasis, appear increasingly. With the development of the Belt and Road Initiative, the transmission risks of these diseases are more increased. The purpose of this paper is to describe the experience and results of parasitic disease prevention and control in China, understand the present parasitic disease epidemic situation of the Belt and Road Initiative related countries, analyze the transmission risks of important parasitic diseases, and present some relevant suggestions, so as to provide the evidence for the health administrative department formulating the prevention and control strategies of such parasitic diseases timely and effectively.

The Alzheimer’s Disease Neuroimaging Initiative Informatics Core: A Decade in Review

PubMed Central

Toga, Arthur W.; Crawford, Karen L.

2015-01-01

The Informatics Core of the Alzheimer’s Diseases Neuroimaging Initiative (ADNI) has coordinated data integration and dissemination for a continually growing and complex dataset in which both data contributors and recipients span institutions, scientific disciplines and geographic boundaries. This article provides an update on the accomplishments and future plans. PMID:26194316

PRINCESS: Privacy-protecting Rare disease International Network Collaboration via Encryption through Software guard extensionS

PubMed Central

Chen, Feng; Wang, Shuang; Jiang, Xiaoqian; Ding, Sijie; Lu, Yao; Kim, Jihoon; Sahinalp, S. Cenk; Shimizu, Chisato; Burns, Jane C.; Wright, Victoria J.; Png, Eileen; Hibberd, Martin L.; Lloyd, David D.; Yang, Hai; Telenti, Amalio; Bloss, Cinnamon S.; Fox, Dov; Lauter, Kristin; Ohno-Machado, Lucila

2017-01-01

Abstract Motivation: We introduce PRINCESS, a privacy-preserving international collaboration framework for analyzing rare disease genetic data that are distributed across different continents. PRINCESS leverages Software Guard Extensions (SGX) and hardware for trustworthy computation. Unlike a traditional international collaboration model, where individual-level patient DNA are physically centralized at a single site, PRINCESS performs a secure and distributed computation over encrypted data, fulfilling institutional policies and regulations for protected health information. Results: To demonstrate PRINCESS’ performance and feasibility, we conducted a family-based allelic association study for Kawasaki Disease, with data hosted in three different continents. The experimental results show that PRINCESS provides secure and accurate analyses much faster than alternative solutions, such as homomorphic encryption and garbled circuits (over 40 000× faster). Availability and Implementation: https://github.com/achenfengb/PRINCESS_opensource Contact: shw070@ucsd.edu Supplementary information: Supplementary data are available at Bioinformatics online. PMID:28065902

Bilateral subthalamic deep brain stimulation initial impact on nonmotor and motor symptoms in Parkinson's disease

PubMed Central

Kurcova, Sandra; Bardon, Jan; Vastik, Miroslav; Vecerkova, Marketa; Frolova, Monika; Hvizdosova, Lenka; Nevrly, Martin; Mensikova, Katerina; Otruba, Pavel; Krahulik, David; Kurca, Egon; Sivak, Stefan; Zapletalova, Jana; Kanovsky, Petr

2018-01-01

Abstract Numerous studies document significant improvement in motor symptoms in patients with Parkinson's disease (PD) after deep brain stimulation of the subthalamic nucleus (STN-DBS). However, little is known about the initial effects of STN-DBS on nonmotor domains. Our objective was to elucidate the initial effects of STN-DBS on non-motor and motor symptoms in PD patients in a 4-month follow-up. This open prospective study followed 24 patients with PD who underwent STN-DBS. The patients were examined using dedicated rating scales preoperatively and at 1 and 4 months following STN-DBS to determine initial changes in motor and nonmotor symptoms. Patients at month 1 after STN-DBS had significantly reduced the Parkinson's disease Questionnaire scores (P = .018) and Scales for Outcomes in Parkinson's disease – Autonomic scores (P = .002); these scores had increased at Month 4 after DBS-STN. Nonmotor Symptoms Scale for Parkinson's Disease had improved significantly at Month 1 (P < .001); at Month 4, it remained significantly lower than before stimulation (P = .036). There was no significant difference in The Parkinson's Disease Sleep Scaleat Month 1 and significant improvement at Month 4 (P = .026). There were no significant changes in The Female Sexual Function Index or International Index of Erectile Function. Movement Disorder Society Unified Parkinson's Disease Rating Scale, Part III scores show significant improvements at Month 1 (P < .001) and at Month 4 (P < .001). STN-DBS in patients with advanced PD clearly improves not only motor symptoms, but also several domains of nonmotor functions, namely sleep, autonomic functions and quality of life quickly following the start of stimulation. PMID:29384860

The Alzheimer's Prevention Initiative Generation Program: Evaluating CNP520 Efficacy in the Prevention of Alzheimer's Disease.

PubMed

Lopez Lopez, C; Caputo, A; Liu, F; Riviere, M E; Rouzade-Dominguez, M-L; Thomas, R G; Langbaum, J B; Lenz, R; Reiman, E M; Graf, A; Tariot, P N

2017-01-01

Alzheimer's disease pathology begins decades before the onset of clinical symptoms. This provides an opportunity for interventional clinical trials to potentially delay or prevent the onset of cognitive impairment or dementia. CNP520 (a beta-site-amyloid precursor protein-cleaving enzyme inhibitor) is in clinical development for the treatment of preclinical Alzheimer's disease under the Alzheimer's Prevention Initiative Generation Program. The Alzheimer's Prevention Initiative is a public-private partnership intended to accelerate the evaluation of Alzheimer's disease prevention therapies. The Generation Program comprises two pivotal phase II/III studies with similar designs to assess the efficacy and safety of investigational treatments in a cognitively unimpaired population at increased risk for developing Alzheimer's disease based on age and apolipoprotein E (APOE) genotype (i.e., presence of the APOE ε4 allele). The program has been designed to maximize benefit to Alzheimer's disease research. Generation Study 1 (NCT02565511) and Generation Study 2 (NCT03131453) are currently enrolling; their key features are presented here.

77 FR 25180 - Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Initial Review

Federal Register 2010, 2011, 2012, 2013, 2014

2012-04-27

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Centers for Disease Control and Prevention Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Initial Review The meeting announced below concerns Evaluation of Dengue Epidemiology, Outcomes, and Prevention in Sentinel...

78 FR 15015 - Disease, Disability, and Injury Prevention and Control Special Emphasis Panels (SEP): Initial Review

Federal Register 2010, 2011, 2012, 2013, 2014

2013-03-08

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Centers for Disease Control and Prevention Disease, Disability, and Injury Prevention and Control Special Emphasis Panels (SEP): Initial Review The meeting announced below concerns Epidemiology, Prevention and Treatment of Influenza and other Respiratory...

78 FR 28221 - Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Initial Review

Federal Register 2010, 2011, 2012, 2013, 2014

2013-05-14

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Centers for Disease Control and Prevention Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Initial Review The meeting announced below concerns Youth Violence Training and Technical Assistance, Funding Opportunity Announcement...

Adult-onset Still's disease initially thought to be an odontogenic infection: A case report.

PubMed

Hino, Shunsuke; Nakamura, Satoshi; Kaneko, Takahiro; Horie, Norio; Shimoyama, Tetsuo

2018-06-01

To present a case of Adult-onset Still's disease (AOSD) initially suspected to be odontogenic inflammation. Adult-onset Still's disease is a rare, complex autoinflammatory disease and a known cause of fever of unknown origin. The patient had both a fever and dental pain. Following meticulous examination, the patient was diagnosed with AOSD. Clinicians should keep in mind that a patient such as AOSD may visit their clinics. © 2018 John Wiley & Sons A/S and The Gerodontology Association. Published by John Wiley & Sons Ltd.

77 FR 291 - Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Initial Review

Federal Register 2010, 2011, 2012, 2013, 2014

2012-01-04

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Centers for Disease Control and Prevention Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Initial Review The meeting announced below concerns National HIV Behavioral Surveillance For Young Men Who Have Sex With Men, Funding...

Spontaneous coronary artery dissection: a disease-specific, social networking community-initiated study.

PubMed

Tweet, Marysia S; Gulati, Rajiv; Aase, Lee A; Hayes, Sharonne N

2011-09-01

To develop and assess the feasibility of a novel method for identification, recruitment, and retrospective and prospective evaluation of patients with rare conditions. This pilot study is a novel example of "patient-initiated research." After being approached by several members of an international disease-specific support group on a social networking site, we used it to identify patients who had been diagnosed as having at least 1 episode of spontaneous coronary artery dissection and recruited them to participate in a clinical investigation of their condition. Medical records were collected and reviewed, the original diagnosis was independently confirmed by review of imaging studies, and health status (both interval and current) was assessed via specially designed questionnaires and validated assessment tools. Recruitment of all 12 participants was complete within 1 week of institutional review board approval (March 18, 2010). Data collection was completed November 18, 2010. All participants completed the study questionnaires and provided the required medical records and coronary angiograms and ancillary imaging data. This study involving patients with spontaneous coronary artery dissection demonstrates the feasibility of and is a successful model for developing a "virtual" multicenter disease registry through disease-specific social media networks to better characterize an uncommon condition. This study is a prime example of patient-initiated research that could be used by other health care professionals and institutions.

Replication Validity of Initial Association Studies: A Comparison between Psychiatry, Neurology and Four Somatic Diseases

PubMed Central

Dumas-Mallet, Estelle; Button, Katherine; Boraud, Thomas; Munafo, Marcus; Gonon, François

2016-01-01

Context There are growing concerns about effect size inflation and replication validity of association studies, but few observational investigations have explored the extent of these problems. Objective Using meta-analyses to measure the reliability of initial studies and explore whether this varies across biomedical domains and study types (cognitive/behavioral, brain imaging, genetic and “others”). Methods We analyzed 663 meta-analyses describing associations between markers or risk factors and 12 pathologies within three biomedical domains (psychiatry, neurology and four somatic diseases). We collected the effect size, sample size, publication year and Impact Factor of initial studies, largest studies (i.e., with the largest sample size) and the corresponding meta-analyses. Initial studies were considered as replicated if they were in nominal agreement with meta-analyses and if their effect size inflation was below 100%. Results Nominal agreement between initial studies and meta-analyses regarding the presence of a significant effect was not better than chance in psychiatry, whereas it was somewhat better in neurology and somatic diseases. Whereas effect sizes reported by largest studies and meta-analyses were similar, most of those reported by initial studies were inflated. Among the 256 initial studies reporting a significant effect (p<0.05) and paired with significant meta-analyses, 97 effect sizes were inflated by more than 100%. Nominal agreement and effect size inflation varied with the biomedical domain and study type. Indeed, the replication rate of initial studies reporting a significant effect ranged from 6.3% for genetic studies in psychiatry to 86.4% for cognitive/behavioral studies. Comparison between eight subgroups shows that replication rate decreases with sample size and “true” effect size. We observed no evidence of association between replication rate and publication year or Impact Factor. Conclusion The differences in reliability

Is tree loss associated with cardiovascular-disease risk in the Women's Health Initiative? A natural experiment

Treesearch

Geoffrey H. Donovan; Yvonne L. Michael; Demetrios Gatziolis; Jeffrey P. Prestemon; Eric A. Whitsel

2015-01-01

Data from the Women's Health Initiative were used to quantify the relationship between the loss of trees to an invasive forest pest—the emerald ash borer—and cardiovascular disease. We estimated semi- parametric Cox proportional hazards model of time to cardiovascular disease, adjusting for confounders. We defined the incidence of cardiovascular disease as acute...

Magnetic resonance imaging in Alzheimer's Disease Neuroimaging Initiative 2.

PubMed

Jack, Clifford R; Barnes, Josephine; Bernstein, Matt A; Borowski, Bret J; Brewer, James; Clegg, Shona; Dale, Anders M; Carmichael, Owen; Ching, Christopher; DeCarli, Charles; Desikan, Rahul S; Fennema-Notestine, Christine; Fjell, Anders M; Fletcher, Evan; Fox, Nick C; Gunter, Jeff; Gutman, Boris A; Holland, Dominic; Hua, Xue; Insel, Philip; Kantarci, Kejal; Killiany, Ron J; Krueger, Gunnar; Leung, Kelvin K; Mackin, Scott; Maillard, Pauline; Malone, Ian B; Mattsson, Niklas; McEvoy, Linda; Modat, Marc; Mueller, Susanne; Nosheny, Rachel; Ourselin, Sebastien; Schuff, Norbert; Senjem, Matthew L; Simonson, Alix; Thompson, Paul M; Rettmann, Dan; Vemuri, Prashanthi; Walhovd, Kristine; Zhao, Yansong; Zuk, Samantha; Weiner, Michael

2015-07-01

Alzheimer's Disease Neuroimaging Initiative (ADNI) is now in its 10th year. The primary objective of the magnetic resonance imaging (MRI) core of ADNI has been to improve methods for clinical trials in Alzheimer's disease (AD) and related disorders. We review the contributions of the MRI core from present and past cycles of ADNI (ADNI-1, -Grand Opportunity and -2). We also review plans for the future-ADNI-3. Contributions of the MRI core include creating standardized acquisition protocols and quality control methods; examining the effect of technical features of image acquisition and analysis on outcome metrics; deriving sample size estimates for future trials based on those outcomes; and piloting the potential utility of MR perfusion, diffusion, and functional connectivity measures in multicenter clinical trials. Over the past decade the MRI core of ADNI has fulfilled its mandate of improving methods for clinical trials in AD and will continue to do so in the future. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Racial/Ethnic Differences in the Incidence of Kawasaki Syndrome among Children in Hawai‘i

PubMed Central

Christensen, Krista Y; Belay, Ermias D; Steiner, Claudia A; Effler, Paul V; Miyamura, Jill; Forbes, Susan; Schonberger, Lawrence B; Melish, Marian

2010-01-01

Objective To describe the occurrence of Kawasaki syndrome (KS) among different racial/ethnic groups in Hawai‘i. Methods Retrospective analysis of children <18 years of age, with a focus on children <5 years of age, living in Hawai‘i who were hospitalized with KS using the 1996–2006 Hawai‘i State Inpatient Data. Results Children <5 years of age accounted for 84% of the 528 patients <18 years of age with KS. The average annual incidence among this age group was 50.4 per 100,000 children <5 years of age, ranging from 45.5 to 56.5. Asian and Pacific Islander children accounted for 92% of the children <5 years of age with KS during the study period; the average annual incidence was 62.9 per 100,000. Within this group, Japanese children had the highest incidence (210.5), followed by Native Hawaiian children (86.9), other Asian children (84.9), and Chinese children (83.2). The incidence for white children (13.7) was lower than for these racial/ethnic groups. The median age of KS admission for children <5 years of age was 21 months overall, 24 months for Japanese children, 14.5 months for Native Hawaiian children and 26.5 months for white children. Conclusions The high average annual KS incidence for children <5 years of age in Hawai‘i compared to the rest of the United States population reflects an increased KS incidence among Asian and Pacific Islander children, especially Japanese children. The incidence for white children was slightly higher than or similar to that generally reported nationwide. PMID:20845285

The Alzheimer's Disease Neuroimaging Initiative 3: Continued innovation for clinical trial improvement.

PubMed

Weiner, Michael W; Veitch, Dallas P; Aisen, Paul S; Beckett, Laurel A; Cairns, Nigel J; Green, Robert C; Harvey, Danielle; Jack, Clifford R; Jagust, William; Morris, John C; Petersen, Ronald C; Salazar, Jennifer; Saykin, Andrew J; Shaw, Leslie M; Toga, Arthur W; Trojanowski, John Q

2017-05-01

The overall goal of the Alzheimer's Disease Neuroimaging Initiative (ADNI) is to validate biomarkers for Alzheimer's disease (AD) clinical trials. ADNI-3, which began on August 1, 2016, is a 5-year renewal of the current ADNI-2 study. ADNI-3 will follow current and additional subjects with normal cognition, mild cognitive impairment, and AD using innovative technologies such as tau imaging, magnetic resonance imaging sequences for connectivity analyses, and a highly automated immunoassay platform and mass spectroscopy approach for cerebrospinal fluid biomarker analysis. A Systems Biology/pathway approach will be used to identify genetic factors for subject selection/enrichment. Amyloid positron emission tomography scanning will be standardized using the Centiloid method. The Brain Health Registry will help recruit subjects and monitor subject cognition. Multimodal analyses will provide insight into AD pathophysiology and disease progression. ADNI-3 will aim to inform AD treatment trials and facilitate development of AD disease-modifying treatments. Copyright © 2016 the Alzheimer's Association. Published by Elsevier Inc. All rights reserved.

The Alzheimer's Disease Neuroimaging Initiative 3: Continued innovation for clinical trial improvement

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

Weiner, Michael W.; Veitch, Dallas P.; Aisen, Paul S.

Overall, the goal of the Alzheimer's Disease Neuroimaging Initiative (ADNI) is to validate biomarkers for Alzheimer's disease (AD) clinical trials. ADNI-3, which began on August 1, 2016, is a 5-year renewal of the current ADNI-2 study. ADNI-3 will follow current and additional subjects with normal cognition, mild cognitive impairment, and AD using innovative technologies such as tau imaging, magnetic resonance imaging sequences for connectivity analyses, and a highly automated immunoassay platform and mass spectroscopy approach for cerebrospinal fluid biomarker analysis. A Systems Biology/pathway approach will be used to identify genetic factors for subject selection/enrichment. Amyloid positron emission tomography scanning willmore » be standardized using the Centiloid method. The Brain Health Registry will help recruit subjects and monitor subject cognition. Multimodal analyses will provide insight into AD pathophysiology and disease progression. Finally, ADNI-3 will aim to inform AD treatment trials and facilitate development of AD disease-modifying treatments.« less

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.

Disease progression model in subjects with mild cognitive impairment from the Alzheimer's disease neuroimaging initiative: CSF biomarkers predict population subtypes

PubMed Central

Samtani, Mahesh N; Raghavan, Nandini; Shi, Yingqi; Novak, Gerald; Farnum, Michael; Lobanov, Victor; Schultz, Tim; Yang, Eric; DiBernardo, Allitia; Narayan, Vaibhav A

2013-01-01

AIM The objective is to develop a semi-mechanistic disease progression model for mild cognitive impairment (MCI) subjects. The model aims to describe the longitudinal progression of ADAS-cog scores from the Alzheimer's disease neuroimaging initiative trial that had data from 198 MCI subjects with cerebrospinal fluid (CSF) information who were followed for 3 years. METHOD Various covariates were tested on disease progression parameters and these variables fell into six categories: imaging volumetrics, biochemical, genetic, demographic, cognitive tests and CSF biomarkers. RESULTS CSF biomarkers were associated with both baseline disease score and disease progression rate in subjects with MCI. Baseline disease score was also correlated with atrophy measured using hippocampal volume. Progression rate was also predicted by executive functioning as measured by the Trail B-test. CONCLUSION CSF biomarkers have the ability to discriminate MCI subjects into sub-populations that exhibit markedly different rates of disease progression on the ADAS-cog scale. These biomarkers can therefore be utilized for designing clinical trials enriched with subjects that carry the underlying disease pathology. PMID:22534009

Advances in paediatrics in 2016: current practices and challenges in allergy, autoimmune diseases, cardiology, endocrinology, gastroenterology, infectious diseases, neonatology, nephrology, neurology, nutrition, pulmonology.

PubMed

Caffarelli, Carlo; Santamaria, Francesca; Di Mauro, Dora; Mastrorilli, Carla; Montella, Silvia; Bernasconi, Sergio

2017-09-16

This review reports main progresses in various pediatric issues published in Italian Journal of Pediatrics and in international journals in 2016. New insights in clinical features or complications of several disorders may be useful for our better understanding. They comprise severe asthma, changing features of lupus erythematosus from birth to adolescence, celiac disease, functional gastrointestinal disorders, Moebius syndrome, recurrent pneumonia. Risk factors for congenital heart defects, Kawasaki disease have been widely investigated. New diagnostic tools are available for ascertaining brucellosis, celiac disease and viral infections. The usefulness of aCGH as first-tier test is confirmed in patients with neurodevelopmental disorders. Novel information have been provided on the safety of milk for infants. Recent advances in the treatment of common disorders, including neonatal respiratory distress syndrome, hypo-glycemia in newborns, atopic dermatitis, constipation, cyclic vomiting syndrome, nephrotic syndrome, diabetes mellitus, regurgitation, short stature, secretions in children with cerebral palsy have been reported. Antipyretics treatment has been updated by national guidelines and studies have excluded side effects (e.g. asthma risk during acetaminophen therapy). Vaccinations are a painful event and several options are reported to prevent this pain. Adverse effects due to metabolic abnormalities are reported for second generation antipsychotic drugs.

Carpal spasm in a girl as initial presentation of celiac disease: a case report.

PubMed

Ramosaj-Morina, Atifete; Keka-Sylaj, A; Hasbahta, V; Baloku-Zejnullahu, A; Azemi, M; Zunec, R

2017-09-04

Celiac disease is an immune-mediated disorder elicited by ingestion of gluten in genetically susceptible persons. This disorder is characterized by specific histological changes of the small intestine mucosa resulting in malabsorption. This case was written up as it was an unusual and dramatic presentation of celiac disease. We report the case of a 3-year-old Albanian girl who presented at our clinic with carpal spasms and hand paresthesia. A physical examination at admission revealed a relatively good general condition and body weight of 10.5 kg (10 percentile). Carpal spasms and paresthesias of her extremities were present. Neuromuscular irritability was demonstrated by positive Chvostek and Trousseau signs. Blood tests showed severe hypocalcemia with a total serum calcium of 1.2 mmol/L (normal range 2.12 to 2.55 mmol/L), ionized calcium of 0.87 (normal range 1.11 to 1.30 mmol/L), and 24-hour urine calcium excretion of 9.16 mmol (normal range female <6.2 mmol/day). Among other tests, screening for celiac disease was performed: antigliadin immunoglobulin A, anti-tissue transglutaminase, and anti-endomysial immunoglobulin A antibodies were positive. A duodenal biopsy revealed lymphocyte infiltration, crypt hyperplasia, and villous atrophy compatible with celiac disease grade IIIb according to the Marsh classification. Following the diagnosis of celiac disease, human leukocyte antigen typing was performed, giving a definite diagnosis of celiac disease. She was started on a gluten-free diet. Due to failure to follow a gluten-free diet, episodes of carpal spasms appeared again. Unfortunately, at the age of 7 years she presents with delayed psychophysical development. Although hypocalcemia is a common finding in celiac disease, hypocalcemic carpal spasm is a rare initial manifestation of the disease. Therefore, the possibility of celiac disease should be considered in patients with repeated carpal spasms that seem unduly difficult to treat. This should be

PRINCESS: Privacy-protecting Rare disease International Network Collaboration via Encryption through Software guard extensionS.

PubMed

Chen, Feng; Wang, Shuang; Jiang, Xiaoqian; Ding, Sijie; Lu, Yao; Kim, Jihoon; Sahinalp, S Cenk; Shimizu, Chisato; Burns, Jane C; Wright, Victoria J; Png, Eileen; Hibberd, Martin L; Lloyd, David D; Yang, Hai; Telenti, Amalio; Bloss, Cinnamon S; Fox, Dov; Lauter, Kristin; Ohno-Machado, Lucila

2017-03-15

We introduce PRINCESS, a privacy-preserving international collaboration framework for analyzing rare disease genetic data that are distributed across different continents. PRINCESS leverages Software Guard Extensions (SGX) and hardware for trustworthy computation. Unlike a traditional international collaboration model, where individual-level patient DNA are physically centralized at a single site, PRINCESS performs a secure and distributed computation over encrypted data, fulfilling institutional policies and regulations for protected health information. To demonstrate PRINCESS' performance and feasibility, we conducted a family-based allelic association study for Kawasaki Disease, with data hosted in three different continents. The experimental results show that PRINCESS provides secure and accurate analyses much faster than alternative solutions, such as homomorphic encryption and garbled circuits (over 40 000× faster). https://github.com/achenfengb/PRINCESS_opensource. shw070@ucsd.edu. Supplementary data are available at Bioinformatics online. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com

Spontaneous Coronary Artery Dissection: A Disease-Specific, Social Networking Community–Initiated Study

PubMed Central

Tweet, Marysia S.; Gulati, Rajiv; Aase, Lee A.; Hayes, Sharonne N.

2011-01-01

OBJECTIVE: To develop and assess the feasibility of a novel method for identification, recruitment, and retrospective and prospective evaluation of patients with rare conditions. PATIENTS AND METHODS: This pilot study is a novel example of “patient-initiated research.” After being approached by several members of an international disease-specific support group on a social networking site, we used it to identify patients who had been diagnosed as having at least 1 episode of spontaneous coronary artery dissection and recruited them to participate in a clinical investigation of their condition. Medical records were collected and reviewed, the original diagnosis was independently confirmed by review of imaging studies, and health status (both interval and current) was assessed via specially designed questionnaires and validated assessment tools. RESULTS: Recruitment of all 12 participants was complete within 1 week of institutional review board approval (March 18, 2010). Data collection was completed November 18, 2010. All participants completed the study questionnaires and provided the required medical records and coronary angiograms and ancillary imaging data. CONCLUSION: This study involving patients with spontaneous coronary artery dissection demonstrates the feasibility of and is a successful model for developing a “virtual” multicenter disease registry through disease-specific social media networks to better characterize an uncommon condition. This study is a prime example of patient-initiated research that could be used by other health care professionals and institutions. PMID:21878595

Delays in Initiation of Disease-Modifying Therapy in Rheumatoid Arthritis Patients: Data from a US-Based Registry.

PubMed

Pappas, Dimitrios A; Kent, Jeffrey D; Greenberg, Jeffrey D; Mason, Marc A; Kremer, Joel M; Holt, Robert J

2015-12-01

The goal of this study was to evaluate how frequently rheumatoid arthritis (RA) therapy is instituted promptly and to describe the characteristics of patients who are not treated early upon diagnosis. The percentage of patients who at the time of enrollment in the Corrona registry were not receiving any RA-directed therapy was evaluated and their characteristics were summarized. The time to subsequent initiation of any RA-directed therapy was also estimated. Among 35,485 patients enrolled in Corrona, 34,735 (97.9%) were on appropriate therapy for RA and 750 (2.1%) had no history of any RA-directed therapy at time of enrollment. Among patients without any history of RA-directed therapy, the overall disease duration was 5.5 ± 9.0 years, with only 50.7% of patients having early disease (duration ≤1 year). Patients with no history of directed RA therapy did not have lower disease activity at enrollment compared with those receiving therapy. Clinical Disease Activity Index (CDAI) was 18.3 ± 15.0; 34% of patients had high and 27.6% moderate disease activity by CDAI. Patients were followed for a median (95% CI) time of 29.5 months (24.6-33.8). During the follow-up period, 372 out of 750 (49.6%) patients initiated RA-directed therapy. The median time to initiation of any RA-directed therapy was 12.1 months (95% CI 9.3-14.8). In this registry analysis, approximately 98% of patients were on appropriate RA therapy for their RA. However, a minority of patients with RA did not have a history of receiving disease-modifying therapy within a mean of approximately 5 years of RA onset and approximately 50% of them did not initiate any therapy within 12 months of registry follow-up. This delay in therapy did not appear to be related to a better controlled, or lower, RA disease activity state at the time of enrollment in the registry. Corrona, LLC.

The Alzheimer's Disease Neuroimaging Initiative (ADNI): MRI Methods

PubMed Central

Jack, Clifford R.; Bernstein, Matt A.; Fox, Nick C.; Thompson, Paul; Alexander, Gene; Harvey, Danielle; Borowski, Bret; Britson, Paula J.; Whitwell, Jennifer L.; Ward, Chadwick; Dale, Anders M.; Felmlee, Joel P.; Gunter, Jeffrey L.; Hill, Derek L.G.; Killiany, Ron; Schuff, Norbert; Fox-Bosetti, Sabrina; Lin, Chen; Studholme, Colin; DeCarli, Charles S.; Krueger, Gunnar; Ward, Heidi A.; Metzger, Gregory J.; Scott, Katherine T.; Mallozzi, Richard; Blezek, Daniel; Levy, Joshua; Debbins, Josef P.; Fleisher, Adam S.; Albert, Marilyn; Green, Robert; Bartzokis, George; Glover, Gary; Mugler, John; Weiner, Michael W.

2008-01-01

The Alzheimer's Disease Neuroimaging Initiative (ADNI) is a longitudinal multisite observational study of healthy elders, mild cognitive impairment (MCI), and Alzheimer's disease. Magnetic resonance imaging (MRI), (18F)-fluorode-oxyglucose positron emission tomography (FDG PET), urine serum, and cerebrospinal fluid (CSF) biomarkers, as well as clinical/psychometric assessments are acquiredat multiple time points. All data will be cross-linked and made available to the general scientific community. The purpose of this report is to describe the MRI methods employed in ADNI. The ADNI MRI core established specifications thatguided protocol development. A major effort was devoted toevaluating 3D T1-weighted sequences for morphometric analyses. Several options for this sequence were optimized for the relevant manufacturer platforms and then compared in a reduced-scale clinical trial. The protocol selected for the ADNI study includes: back-to-back 3D magnetization prepared rapid gradient echo (MP-RAGE) scans; B1-calibration scans when applicable; and an axial proton density-T2 dual contrast (i.e., echo) fast spin echo/turbo spin echo (FSE/TSE) for pathology detection. ADNI MRI methods seek to maximize scientific utility while minimizing the burden placed on participants. The approach taken in ADNI to standardization across sites and platforms of the MRI protocol, postacquisition corrections, and phantom-based monitoring of all scanners could be used as a model for other multisite trials. PMID:18302232

Superantigens and their association with dermatological inflammatory diseases: facts and hypotheses.

PubMed

Jappe, U

2000-01-01

Superantigens have been suggested to play an important role in the pathogenesis of several inflammatory skin diseases as well as systemic diseases such as atopic dermatitis, psoriasis, vasculitis, T-cell lymphoma and autoimmune diseases. Infections often precede the onset and relapse of these diseases, and antibiotic treatment with or without additional glucocorticosteroids and immunoglobulins is occasionally successful. Superantigens are microbial proteins that are able to stimulate up to 20% of the naive T-cell population in a non-specific way. They are produced by gram-positive and -negative bacteria as well as by viruses, parasites and yeasts. The importance of the pathogenic role of superantigens is determined by the potency to induce inflammation by extensive cytokine release after T-cell stimulation and/or T-cell-mediated cytotoxicity and, thereby, tissue damage. Furthermore, superantigens may be able to induce autoimmune processes by stimulation of autoreactive T-cells as well as autoantibody production by stimulation of B-cells. Among the diseases associated with superantigens, atopic dermatitis, guttate and chronic plaque psoriasis, as well as Kawasaki disease, are by far the best-characterized. Nevertheless, conflicting results have been obtained and formal proof of a pathogenic role of superantigens in these diseases is still lacking. The aim of this review is to summarize the data on superantigens in terms of their distribution in microorganisms, their interactions with the adaptive immune system and their contribution to skin pathology.

Development of Interstitial Lung Disease after Initiation of Apixaban Anticoagulation Therapy.

PubMed

Tomari, Shinya; Homma, Kazunari; Noguchi, Teruo; Aiba, Takeshi; Matsuki, Takayuki; Suzuki, Rieko; Koga, Masatoshi; Takigami, Masao; Tagawa, Hiroshi; Hashimoto, Taisuke; Toyoda, Kazunori

2016-07-01

Nonvitamin K antagonist oral anticoagulants may cause interstitial lung disease (ILD) similar to that seen for other cardiovascular drugs. The aim of this study was to determine trends and medical conditions associated with ILD in patients taking apixaban. A single-center observational survey conducted between February 2013 and May 2015 examined patients who developed ILD after initiation of apixaban administration. Chest computed tomography showed that 4 (~.45%) out of approximately 870 apixaban users developed ILD. All patients were elderly Japanese men with decreased creatinine clearance who had nonvalvular atrial fibrillation. Three of the four were confirmed smokers, whereas three had a history of lung disease. Dyspnea occurred during the initial week after starting apixaban administration in 3 patients and at 90 days in 1 patient. All patients underwent methylprednisolone pulse therapy, with three requiring mechanical ventilation. Although 2 patients recovered, the other two died of respiratory failure. Development of ILD during anticoagulation with apixaban is not rare. When apixaban is administered in elderly high-risk patients, subjects need to be carefully monitored for respiratory symptoms. As drug-induced ILD is often reported in Japan, further studies that clarify if these types of cases are common in countries other than Japan will also need to be undertaken. Copyright © 2016 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Multiplex method for initial complex testing of antibodies to blood transmitted diseases agents.

PubMed

Poltavchenko, Alexander G; Nechitaylo, Oleg V; Filatov, Pavel V; Ersh, Anna V; Gureyev, Vadim N

2016-10-01

Initial screening of donors and population at high risk of infection with blood transmitted diseases involves a number of analyses using monospesific diagnostic systems, and therefore is expensive labor- and time-consuming process. The goal of this work is to construct a multiplex test enabling to carry out rapid initial complex testing at a low price. The paper describes a kit making it possible to detect simultaneously antibodies to six agents of the most significant blood transmitted diseases: HIV virus, hepatitis B and C viruses, cytomegalovirus, T. pallidum and T. gondii in blood products. The kit comprises multiplex dot-immunoassay based on plane protein arrays (immune chips) using colloidal gold conjugates and silver development. It provides an opportunity to carry out complex analysis within 70min at room temperature, and there is no need of well-qualified personnel. We compared laboratory findings of the kit with monospecific kits for ELISA produced by two Russian commercial companies. Dot-assay results correlate well with data obtained using commercial kits for ELISA. Furthermore, multiplex analysis is quicker and cheaper in comparison with ELISA and can be carried out in non-laboratory conditions. The kit for multiplex dot-immunoassay of antibodies to blood transmitted agents can significantly simplify initial complex testing. Copyright © 2016 Elsevier B.V. All rights reserved.

Autopsy-confirmed hippocampal-sparing Alzheimer's disease with delusional jealousy as initial manifestation.

PubMed

Fujishiro, Hiroshige; Iritani, Shuji; Hattori, Miho; Sekiguchi, Hirotaka; Matsunaga, Shinji; Habuchi, Chikako; Torii, Youta; Umeda, Kentaro; Ozaki, Norio; Yoshida, Mari; Fujita, Kiyoshi

2015-09-01

Alzheimer's disease (AD) is clinically characterized by gradual onset over years with worsening of cognition. The initial and most prominent cognitive deficit is commonly memory dysfunction. However, a subset of AD cases has less hippocampal atrophy than would be expected relative to the predominance of cortical atrophy. These hippocampal-sparing cases have distinctive clinical features, including the presence of focal cortical clinical syndromes. Given that previous studies have indicated that severe hippocampal atrophy corresponds to prominent loss of episodic memory, it is likely that memory impairment is initially absent in hippocampal-sparing AD cases. Here, we report on a patient with an 8-year history of delusional jealousy with insidious onset who was clinically diagnosed as possible AD and pathologically confirmed to have AD with relatively preserved neurons in the hippocampus. This patient had delusional jealousy with a long pre-dementia stage, which initially was characterized by lack of memory impairment. Head magnetic resonance imaging findings showed preserved hippocampal volume with bilateral enlarged ventricles and mild-to-moderate cortical atrophy. Head single-photon emission computed tomography revealed severely decreased regional cerebral blood flow in the right temporal lobe. The resolution of the delusion was attributed to pharmacotherapy by an acetylcholinesterase inhibitor, suggesting that the occurrence of delusional jealousy was due to the disease process of AD. Although the neural basis of delusional jealousy remains unclear, this hippocampal-sparing AD case may be classified as an atypical presentation of AD. © 2015 The Authors. Psychogeriatrics © 2015 Japanese Psychogeriatric Society.

A Precision Medicine Initiative for Alzheimer's disease: the road ahead to biomarker-guided integrative disease modeling.

PubMed

Hampel, H; O'Bryant, S E; Durrleman, S; Younesi, E; Rojkova, K; Escott-Price, V; Corvol, J-C; Broich, K; Dubois, B; Lista, S

2017-04-01

After intense scientific exploration and more than a decade of failed trials, Alzheimer's disease (AD) remains a fatal global epidemic. A traditional research and drug development paradigm continues to target heterogeneous late-stage clinically phenotyped patients with single 'magic bullet' drugs. Here, we propose that it is time for a paradigm shift towards the implementation of precision medicine (PM) for enhanced risk screening, detection, treatment, and prevention of AD. The overarching structure of how PM for AD can be achieved will be provided through the convergence of breakthrough technological advances, including big data science, systems biology, genomic sequencing, blood-based biomarkers, integrated disease modeling and P4 medicine. It is hypothesized that deconstructing AD into multiple genetic and biological subsets existing within this heterogeneous target population will provide an effective PM strategy for treating individual patients with the specific agent(s) that are likely to work best based on the specific individual biological make-up. The Alzheimer's Precision Medicine Initiative (APMI) is an international collaboration of leading interdisciplinary clinicians and scientists devoted towards the implementation of PM in Neurology, Psychiatry and Neuroscience. It is hypothesized that successful realization of PM in AD and other neurodegenerative diseases will result in breakthrough therapies, such as in oncology, with optimized safety profiles, better responder rates and treatment responses, particularly through biomarker-guided early preclinical disease-stage clinical trials.

Effect of three cueing devices for people with Parkinson's disease with gait initiation difficulties.

PubMed

McCandless, Paula J; Evans, Brenda J; Janssen, Jessie; Selfe, James; Churchill, Andrew; Richards, Jim

2016-02-01

Freezing of gait (FOG) remains one of the most common debilitating aspects of Parkinson's disease and has been linked to injuries, falls and reduced quality of life. Although commercially available portable cueing devices exist claiming to assist with overcoming freezing; their immediate effectiveness in overcoming gait initiation failure is currently unknown. This study investigated the effects of three different types of cueing device in people with Parkinson's disease who experience freezing. Twenty participants with idiopathic Parkinson's disease who experienced freezing during gait but who were able to walk short distances indoors independently were recruited. At least three attempts at gait initiation were recorded using a 10 camera Qualisys motion analysis system and four force platforms. Test conditions were; Laser Cane, sound metronome, vibrating metronome, walking stick and no intervention. During testing 12 of the 20 participants had freezing episodes, from these participants 100 freezing and 91 non-freezing trials were recorded. Clear differences in the movement patterns were seen between freezing and non-freezing episodes. The Laser Cane was most effective cueing device at improving the forwards/backwards and side to side movement and had the least number of freezing episodes. The walking stick also showed significant improvements compared to the other conditions. The vibration metronome appeared to disrupt movement compared to the sound metronome at the same beat frequency. This study identified differences in the movement patterns between freezing episodes and non-freezing episodes, and identified immediate improvements during gait initiation when using the Laser Cane over the other interventions. Copyright © 2015. Published by Elsevier B.V.

Pharmacokinetic and Tolerability Assessment of a Pediatric Oral Formulation of Pentoxifylline in Kawasaki Disease☆

PubMed Central

Best, Brookie M.; Burns, Jane C.; DeVincenzo, John; Phelps, Stephanie J.; Blumer, Jeffrey L.; Wilson, John T.; Capparelli, Edmund V.; Connor, James D.

2003-01-01

Background: In infants and children, treatment of Kawasaki disease (KD) with high-dose intravenous immunoglobulin (IVIG) and acetylsalicylic acid ([ASA] aspirin) diminishes inflammatory response and reduces the risk for coronary artery abnormalities. However, patients with high serum concentrations of tumor necrosis factor (TNF)-alpha, which is associated with vascular damage, may develop coronary artery lesions even with treatment. The hemorheologic agent pentoxifylline blocks the production of TNF-alpha and may be an appropriate adjunctive therapy to IVIG and ASA. Objective: The objective of this study was to assess the pharmacokinetic characteristics and tolerability of a new oral syrup formulation of pentoxifylline as an adjunct to IVIG and ASA in the treatment of KD in children. Methods: Hospitalized boys and girls aged 6 months to 5 years and who were diagnosed with KD within the first 10 days of illness were eligible. Patients were assigned to 1 of 4 pentoxifylline treatment groups, by dose level (dose levels 1, 2, 3, and 4: 10, 15, 20, and 25 mg/kg daily, respectively, divided into 3 doses). Six plasma samples collected at the time the first dose was administered, and 4 samples collected after administration of the last dose on study day 6, were assessed by high-performance liquid chromatography using noncompartmental and 1-compartment pharmacokinetic analyses for pentoxifylline and its active metabolite (M-1). TNF-alpha levels on days 1 and 6 were assessed using electroimmunoassay. Results: Fourteen boys and 10 girls were enrolled. The mean age, body weight, and illness day at study entry were 34.5 months, 13.8 kg, and 6, respectively. Pentoxifylline exhibited nonlinear kinetic characteristics, with median area under the plasma concentration–time curve from time 0 to infinity(AUC0–∞) values of 622, 3428, 8416, and 10,347 ng/mL · h for dose levels 1 to 4, respectively, on study day 1. Pentoxifylline noncompartmental oral clearance and volume of

PENN Biomarker Core of the Alzheimer’s Disease Neuroimaging Initiative

PubMed Central

Shaw, Leslie M.

2009-01-01

There is a pressing need to develop effective prevention and disease-modifying treatments for Alzheimer’s disease (AD), a dreaded affliction whose incidence increases almost logarithmically with age starting at about 65 years. A key need in the field of AD research is the validation of imaging and biochemical biomarkers. Biomarker tests that are shown to reliably predict the disease before it is clinically expressed would permit testing of new therapeutics at the earliest time point possible in order to give the best chance for delaying the onset of dementia in these patients. In this review the current state of AD biochemical biomarker research is discussed. A new set of guidelines for the diagnosis of AD in the research setting places emphasis on the inclusion of selected imaging and biochemical biomarkers, in addition to neuropsychological behavioral testing. Importantly, the revised guidelines were developed to identify patients at the earliest stages prior to full-blown dementia as well as patients with the full spectrum of the disease. The Alzheimer’s Disease Neuroimaging Initiative is a multicenter consortium study that includes as one of its primary goals the development of standardized neuroimaging and biochemical biomarker methods for AD clinical trials, as well as using these to measure changes over time in mildly cognitively impaired patients who convert to AD as compared to the natural variability of these in control subjects and their further change over time in AD patients. Validation of the biomarker results by correlation analyses with neuropsychological and neurobehavioral test data is one of the primary outcomes of this study. This validation data will hopefully provide biomarker test performance needed for effective measurement of the efficacy of new treatment and prevention therapeutic agents. PMID:18097156

Interview with Dr Bernard Pécoul, Executive Director of the Drugs for Neglected Diseases Initiative.

PubMed

Pécoul, Bernard

2009-05-01

A significant number of product-development partnerships have arisen in the past 10 years to tackle diseases that mainly affect developing countries. With their coherent research and development leadership, they have become key players in identifying gaps and overcoming bottlenecks in order to deliver medicines to those who need them most in the developing world. Dr Bernard Pécoul is the Executive Director of one such partnership, the Drugs for Neglected Diseases Initiative (DNDi). Under his leadership, the DNDi has built the largest and most robust R&D portfolio for three of the most neglected diseases. He speaks to Future Medicinal Chemistry about challenges facing neglected disease R&D and the DNDi's ongoing work.

77 FR 42954 - Airworthiness Directives; Boeing Vertol (Type Certificate Currently Held by Columbia Helicopters...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-07-23

...)) and Kawasaki Heavy Industries, Limited Helicopters (Kawasaki) AGENCY: Federal Aviation Administration... Columbia Helicopters, Inc.) and Kawasaki Heavy Industries, Limited Helicopters: Amendment 39-17124; Docket... Heavy Industries, Limited Model KV107-II and KV107-IIA helicopters with an upper collective pitch...

Expanding efforts to address Alzheimer’s disease: The Healthy Brain Initiative

PubMed Central

Anderson, Lynda A.; Egge, Robert

2015-01-01

The growing burden of Alzheimer’s disease underscores the importance of enhancing current public health efforts to address dementia. Public health organizations and entities have substantial opportunities to contribute to efforts underway and to add innovations to the field. The Alzheimer’s Association and the Centers for Disease Control and Prevention worked with a 15-member leadership committee and hundreds of stakeholders to create The Healthy Brain Initiative: The Public Health Road Map for State and National Partnerships, 2013–2018 (Road Map). The actions in the Road Map provide a foundation for the public health community to anticipate and respond to emerging innovations and developments. It will be a challenge to harness the increasingly complex nature of public- and private-sector collaborations. We must strengthen the capacity of public health agencies, leverage partnerships, and find new ways to integrate cognitive functioning into public health efforts. PMID:25088658

Novel mutation at the initiation codon in the Norrie disease gene in two Japanese families.

PubMed

Isashiki, Y; Ohba, N; Yanagita, T; Hokita, N; Doi, N; Nakagawa, M; Ozawa, M; Kuroda, N

1995-01-01

We have identified a new mutation of Norrie disease (ND) gene in two Japanese males from unrelated families; they showed typical ocular features of ND but no mental retardation or hearing impairment. A mutation was found in both patients at the initiation codon of exon 2 of the ND gene (ATG to GTG), with otherwise normal nucleotide sequences. Their mothers had the normal and mutant types of the gene, which was expected for heterozygotes of the disease. The mutation of the initiation codon would cause the failure of ND gene expression or a defect in translation thereby truncating the amino terminus of ND protein. In view of the rarity and marked heterogeneity of mutations in the ND gene, the present apparently unrelated Japanese families who have lived in the same area for over two centuries presumably share the origin of the mutation.

HEALER: homomorphic computation of ExAct Logistic rEgRession for secure rare disease variants analysis in GWAS

PubMed Central

Wang, Shuang; Zhang, Yuchen; Dai, Wenrui; Lauter, Kristin; Kim, Miran; Tang, Yuzhe; Xiong, Hongkai; Jiang, Xiaoqian

2016-01-01

Motivation: Genome-wide association studies (GWAS) have been widely used in discovering the association between genotypes and phenotypes. Human genome data contain valuable but highly sensitive information. Unprotected disclosure of such information might put individual’s privacy at risk. It is important to protect human genome data. Exact logistic regression is a bias-reduction method based on a penalized likelihood to discover rare variants that are associated with disease susceptibility. We propose the HEALER framework to facilitate secure rare variants analysis with a small sample size. Results: We target at the algorithm design aiming at reducing the computational and storage costs to learn a homomorphic exact logistic regression model (i.e. evaluate P-values of coefficients), where the circuit depth is proportional to the logarithmic scale of data size. We evaluate the algorithm performance using rare Kawasaki Disease datasets. Availability and implementation: Download HEALER at http://research.ucsd-dbmi.org/HEALER/ Contact: shw070@ucsd.edu Supplementary information: Supplementary data are available at Bioinformatics online. PMID:26446135

Relationship between history of coronary heart disease at dialysis initiation and onset of events associated with heart disease: a propensity-matched analysis of a prospective cohort study.

PubMed

Inaguma, Daijo; Koide, Shigehisa; Takahashi, Kazuo; Hayashi, Hiroki; Hasegawa, Midori; Yuzawa, Yukio

2017-02-28

Chronic kidney disease (CKD) is an independent risk factor for cardiovascular disease (CVD) events, and a number of reports have shown a relationship between CKD and CVD in pre-dialysis or maintenance dialysis patients. However, few studies have reported serial observations during dialysis initiation and maintenance. Therefore, we examined whether the incidence of heart disease events differed between CKD patients with and without a history of coronary heart disease (CHD) at dialysis initiation. The subjects were patients in the 17 centers participating in the Aichi Cohort Study of Prognosis in Patients Newly Initiated into Dialysis (AICOPP) from October 2011 to September 2013. We excluded nine patients whose outcomes were unknown, as determined by a survey conducted at the end of March 2015. Thus, we enrolled 1,515 subjects into the study. We classified patients into 2 groups according to the history of CHD (i.e., a CHD group and a non-CHD group). Propensity scores (PS) represented the probability of being assigned to a group with or without a history of CHD. Onset of heart disease events and associated mortality and all-cause mortality were compared in PS-matched patients by using the log-rank test for Kaplan-Meier curves. Factors contributing to heart disease events were examined using stepwise multivariate Cox proportional hazards analysis. There were 254 patients in each group after PS-matching. During observation, heart disease events occurred in 85 patients (33.5%) in the CHD group and 48 (18.9%) patients in the non-CHD group. The incidence was significantly higher in the CHD group (p < 0.0001). The CHD group was associated with higher incidence of heart disease events (vs. the non-CHD group, hazard ratio = 1.750, 95% confidence interval = 1.160-2.639). In addition, comorbidities such as diabetes mellitus, low body mass index, and low serum high-density lipoprotein cholesterol were associated with higher incidence of events. History of CHD at

Biventricular hypertrophy and heart failure as initial presentation of Cushing's disease

PubMed Central

Hey, Thomas Morris; Dahl, Jordi Sanchez; Brix, Thomas Heiberg; Søndergaard, Eva Vad

2013-01-01

We present a unique case of a 32-year-old woman with severe biventricular hypertrophy and acute heart failure with reduced left ventricular ejection fraction of 25–30% due to Cushing's disease. The patient was admitted to a specialised cardiac unit and treated with conventional therapy against heart failure. The department of endocrinology was consulted because of clinical suspicion of Cushing's syndrome. Initial biochemistry indicated the presence of adrenocorticotropic hormone (ACTH) dependent Cushing's syndrome and a dexamethasone suppression test confirmed the diagnosis. A cerebral MRI scan revealed a pituitary adenoma and a sinus petrosus inferior catheterisation confirmed increased production of ACTH from the pituitary. The patient was referred to the neurosurgical department and the adenoma was successfully removed by transsphenoidalic catheterisation and ablation. Five months following the initial hospitalisation the patient was nearly in full recovery with respect to her cardiac function and biochemically there were no signs of Cushing's syndrome. PMID:24186856

The Impact of a Community-Based Chronic Disease Prevention Initiative: Evaluation Findings from "Steps to Health King County"

ERIC Educational Resources Information Center

Cheadle, Allen; Bourcier, Emily; Krieger, James; Beery, William; Smyser, Michael; Vinh, Diana V.; Lessler, Dan; Alfonsi, Lorrie

2011-01-01

"Steps to Health King County" ("Steps KC"; Seattle, Washington) was one of 40 community-level initiatives funded in 2003 as part of the "Steps to a HealthierUS" initiative. "Steps KC" goals included reducing the impact of chronic diseases through a comprehensive, coordinated approach and reducing health…

Determinants of variations in initial treatment strategies for stable ischemic heart disease

PubMed Central

Bennell, Maria C.; Qiu, Feng; Kingsbury, Kori J.; Austin, Peter C.; Wijeysundera, Harindra C.

2015-01-01

Background: The ratio of revascularization to medical therapy (referred to herein as the revascularization ratio) for the initial treatment of stable ischemic heart disease varies considerably across hospitals. We conducted a comprehensive study to identify patient, physician and hospital factors associated with variations in the revascularization ratio across 18 cardiac centres in the province of Ontario. We also explored whether clinical outcomes differed between hospitals with high, medium and low ratios. Methods: We identified all patients in Ontario who had stable ischemic heart disease documented by index angiography performed between Oct. 1, 2008, and Sept. 30, 2011, at any of the 18 cardiac centres in the province. We classified patients by initial treatment strategy (medical therapy or revascularization). Hospitals were classified into equal tertiles based on their revascularization ratio. The primary outcome was all-cause mortality. Patient follow-up was until Dec. 31, 2012. Hierarchical logistic regression models identified predictors of revascularization. Multivariable Cox proportional hazards models, with a time-varying covariate for actual treatment received, were used to evaluate the impact of the revascularization ratio on clinical outcomes. Results: Variation in revascularization ratios was twofold across the hospitals. Patient factors accounted for 67.4% of the variation in revascularization ratios. Physician and hospital factors were not significantly associated with the variation. Significant patient-level predictors of revascularization were history of smoking, multivessel disease, high-risk findings on noninvasive stress testing and more severe symptoms of angina (v. no symptoms). Treatment at hospitals with a high revascularization ratio was associated with increased mortality compared with treatment at hospitals with a low ratio (hazard ratio 1.12, 95% confidence interval 1.03–1.21). Interpretation: Most of the variation in

Meningococcal disease in the Asia-Pacific region: Findings and recommendations from the Global Meningococcal Initiative.

PubMed

Borrow, Ray; Lee, Jin-Soo; Vázquez, Julio A; Enwere, Godwin; Taha, Muhamed-Kheir; Kamiya, Hajime; Kim, Hwang Min; Jo, Dae Sun

2016-11-21

The Global Meningococcal Initiative (GMI) is a global expert group that includes scientists, clinicians, and public health officials with a wide range of specialties. The purpose of the Initiative is to promote the global prevention of meningococcal disease (MD) through education, research, and cooperation. The first Asia-Pacific regional meeting was held in November 2014. The GMI reviewed the epidemiology of MD, surveillance, and prevention strategies, and outbreak control practices from participating countries in the Asia-Pacific region.Although, in general, MD is underreported in this region, serogroup A disease is most prominent in low-income countries such as India and the Philippines, while Taiwan, Japan, and Korea reported disease from serogroups C, W, and Y. China has a mixed epidemiology of serogroups A, B, C, and W. Perspectives from countries outside of the region were also provided to provide insight into lessons learnt. Based on the available data and meeting discussions, a number of challenges and data gaps were identified and, as a consequence, several recommendations were formulated: strengthen surveillance; improve diagnosis, typing and case reporting; standardize case definitions; develop guidelines for outbreak management; and promote awareness of MD among healthcare professionals, public health officials, and the general public. Copyright © 2016. Published by Elsevier Ltd.

Initial validation of a healthcare needs scale for young people with congenital heart disease.

PubMed

Chen, Chi-Wen; Ho, Ciao-Lin; Su, Wen-Jen; Wang, Jou-Kou; Chung, Hung-Tao; Lee, Pi-Chang; Lu, Chun-Wei; Hwang, Be-Tau

2018-01-01

To validate the initial psychometric properties of a Healthcare Needs Scale for Youth with Congenital Heart Disease. As the number of patients with congenital heart disease surviving to adulthood increases, the transitional healthcare needs for adolescents and young adults with congenital heart disease require investigation. However, few tools comprehensively identify the healthcare needs of youth with congenital heart disease. A cross-sectional study was employed to examine the psychometric properties of the Healthcare Needs Scale for Youth with Congenital Heart Disease. The sample consisted of 500 patients with congenital heart disease, aged 15-24 years, from paediatric cardiology departments and covered the period from March-August 2015. The patients completed the 25-item Healthcare Needs Scale for Youth with Congenital Heart Disease, the questionnaire on health needs for adolescents and the WHO Quality of Life-BREF. Reliability and construct, concurrent, predictive and known-group validity were examined. The Healthcare Needs Scale for Youth with Congenital Heart Disease includes three dimensions, namely health management, health policy and individual and interpersonal relationships, which consist of 25 items. It demonstrated excellent internal consistency and sound construct, concurrent, predictive and known-group validity. The Healthcare Needs Scale for Youth with Congenital Heart Disease is a psychometrically robust measure of the healthcare needs of youth with congenital heart disease. It has the potential to provide nurses with a means to assess and identify the concerns of youth with congenital heart disease and to help them achieve a successful transition to adult care. © 2017 John Wiley & Sons Ltd.

Variability of Anticipatory Postural Adjustments During Gait Initiation in Individuals With Parkinson Disease.

PubMed

Lin, Cheng-Chieh; Creath, Robert A; Rogers, Mark W

2016-01-01

In people with Parkinson disease (PD), difficulties with initiating stepping may be related to impairments of anticipatory postural adjustments (APAs). Increased variability in step length and step time has been observed in gait initiation in individuals with PD. In this study, we investigated whether the ability to generate consistent APAs during gait initiation is compromised in these individuals. Fifteen subjects with PD and 8 healthy control subjects were instructed to take rapid forward steps after a verbal cue. The changes in vertical force and ankle marker position were recorded via force platforms and a 3-dimensional motion capture system, respectively. Means, standard deviations, and coefficients of variation of both timing and magnitude of vertical force, as well as stepping variables, were calculated. During the postural phase of gait initiation the interval was longer and the force modulation was smaller in subjects with PD. Both the variability of timing and force modulation were larger in subjects with PD. Individuals with PD also had a longer time to complete the first step, but no significant differences were found for the variability of step time, length, and speed between groups. The increased variability of APAs during gait initiation in subjects with PD could affect posture-locomotion coupling, and lead to start hesitation, and even falls. Future studies are needed to investigate the effect of rehabilitation interventions on the variability of APAs during gait initiation in individuals with PD.Video abstract available for more insights from the authors (see Supplemental Digital Content 1, http://links.lww.com/JNPT/A119).

Central nervous system involvement in pediatric rheumatic diseases: current concepts in treatment.

PubMed

Duzova, Ali; Bakkaloglu, Aysin

2008-01-01

Central nervous system (CNS) manifestations are not rare in pediatric rheumatic diseases. They may be a relatively common feature of the disease, as in systemic lupus erythematosus (SLE) and Behçet's disease. Direct CNS involvement of a systemic rheumatic disease, primary CNS vasculitis, indirect involvement secondary to hypertension, hypoxia and metabolic changes, and drug associated adverse events may all result in CNS involvement. We have reviewed the CNS manifestations of SLE, Behçet's disease, Henoch-Schönlein purpura, polyarteritis nodosa, juvenile idiopathic arthritis, juvenile ankylosing spondylitis, familial Mediterranean fever, scleroderma, sarcoidosis, Wegener's granulomatosis, Takayasu's arteritis, CINCA syndrome, Kawasaki disease, and primary CNS vasculitis; and adverse CNS effects of anti-rheumatic drugs in pediatric patients. The manifestations are diverse; ranging from headache, seizures, chorea, changes in personality, depression, memory and concentration problems, cognitive impairment, cerebrovascular accidents to coma, and death. The value of cerebrospinal fluid (CSF) examination (pleocytosis, high level of protein), auto-antibodies in serum and CSF, electroencephalography, neuroimaging with computerized tomography, magnetic resonance imaging, SPECT, PET, and angiography depends on the disease. Brain biopsy is gold standard for the diagnosis of CNS vasculitis, however it may be inconclusive in 25% of cases. A thorough knowledge of the rheumatic diseases and therapy-related adverse events is mandatory for the management of a patient with rheumatic disease and CNS involvement. Severe CNS involvement is associated with poor prognosis, and high mortality rate. High dose steroid and cyclophosphamide (oral or intravenous) are first choice drugs in the treatment; plasmapheresis, IVIG, thalidomide, and intratechal treatment may be valuable in treatment-resistant, and serious cases.

Periodic Paralysis and Encephalopathy as Initial Manifestations of Graves' Disease: Case Report and Review of the Literature.

PubMed

Tsironis, Theocharis; Tychalas, Athanasios; Kiourtidis, Dimitrios; Kountouras, Jannis; Xiromerisiou, Georgia; Rudolf, Jobst; Deretzi, Georgia

2017-07-01

Thyrotoxic periodic paralysis (TPP) is an uncommon complication of Graves' disease, characterized by the triad of acute hypokalemia without total body potassium deficit, episodic muscle paralysis, and thyrotoxicosis. Graves' encephalopathy is an extremely rare form of encephalopathy associated with autoimmune thyroid disease (EAATD), characterized by neuropsychiatric symptoms, increased antithyroid antibodies and cerebrospinal fluid protein concentration, nonspecific electroencephalogram abnormalities, and cortico-responsiveness. Coexistence of both these complications in the same patient has not been reported before. We herein present a 48-year-old white male patient with TPP and encephalopathy as initial presentations of Graves' disease. Flaccid tetraparesis was reversed a few hours after potassium level correction and the patient did not suffer any relapse with the successful pharmaceutical management of the thyroid function. One month later, the patient presented with dizziness and behavioral symptoms, such as inappropriate laughter and anger. Brain magnetic resonance imaging revealed meningeal enhancement and cerebrospinal fluid analysis showed a mild protein increase, with a blood-brain barrier disruption. With the suspicion of EAATD, the patient was treated with high doses of corticosteroids and improved dramatically. To our knowledge this is the first reported coexistence of potentially treatable TPP and EAATD as initial neurological manifestations of Graves' disease, thereby underscoring the necessity of suspicion of possible underlying Graves' disease in patients with acute paralysis and encephalopathy of unclear origin.

77 FR 4047 - Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Initial Review

Federal Register 2010, 2011, 2012, 2013, 2014

2012-01-26

... announced below concerns Epidemiology, Prevention and Treatment of Influenza and Other Respiratory... Diseases in Vietnam, IP12-002, The Incidence of Community Associated Influenza and Other Respiratory... Respiratory Infections in Panama and Central America Region, IP12-006, initial review. In accordance with...

C9orf72 Nucleotide Repeat Structures Initiate Molecular Cascades of Disease

PubMed Central

Haeusler, Aaron R.; Donnelly, Christopher J.; Periz, Goran; Simko, Eric A.J.; Shaw, Patrick G.; Kim, Min-Sik; Maragakis, Nicholas J.; Troncoso, Juan C.; Pandey, Akhilesh; Sattler, Rita; Rothstein, Jeffrey D.; Wang, Jiou

2014-01-01

Summary A hexanucleotide repeat expansion (HRE), (GGGGCC)n, in C9orf72 is the most common genetic cause of the neurodegenerative diseases amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Here we identify a molecular mechanism by which structural polymorphism of the HRE leads to ALS/FTD pathology and defects. The HRE forms DNA and RNA G-quadruplexes with distinct structures and promotes RNA•DNA hybrids (R-loops). The structural polymorphism causes a repeat length-dependent accumulation of transcripts aborted in the HRE region. These transcribed repeats bind to ribonucleoproteins in a conformationdependent manner. Specifically, nucleolin (NCL), an essential nucleolar protein, preferentially binds the HRE G-quadruplex, and patient cells show evidence of nucleolar stress. Our results demonstrate that distinct C9orf72 HRE structural polymorphism at both DNA and RNA levels initiates molecular cascades leading to ALS/FTD pathologies, and provide the basis for a mechanistic model for repeat-associated neurodegenerative diseases. PMID:24598541

C9orf72 nucleotide repeat structures initiate molecular cascades of disease.

PubMed

Haeusler, Aaron R; Donnelly, Christopher J; Periz, Goran; Simko, Eric A J; Shaw, Patrick G; Kim, Min-Sik; Maragakis, Nicholas J; Troncoso, Juan C; Pandey, Akhilesh; Sattler, Rita; Rothstein, Jeffrey D; Wang, Jiou

2014-03-13

A hexanucleotide repeat expansion (HRE), (GGGGCC)n, in C9orf72 is the most common genetic cause of the neurodegenerative diseases amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Here we identify a molecular mechanism by which structural polymorphism of the HRE leads to ALS/FTD pathology and defects. The HRE forms DNA and RNA G-quadruplexes with distinct structures and promotes RNA•DNA hybrids (R-loops). The structural polymorphism causes a repeat-length-dependent accumulation of transcripts aborted in the HRE region. These transcribed repeats bind to ribonucleoproteins in a conformation-dependent manner. Specifically, nucleolin, an essential nucleolar protein, preferentially binds the HRE G-quadruplex, and patient cells show evidence of nucleolar stress. Our results demonstrate that distinct C9orf72 HRE structural polymorphism at both DNA and RNA levels initiates molecular cascades leading to ALS/FTD pathologies, and provide the basis for a mechanistic model for repeat-associated neurodegenerative diseases.

Genome-wide association analysis of secondary imaging phenotypes from the Alzheimer's disease neuroimaging initiative study.

PubMed

Zhu, Wensheng; Yuan, Ying; Zhang, Jingwen; Zhou, Fan; Knickmeyer, Rebecca C; Zhu, Hongtu

2017-02-01

The aim of this paper is to systematically evaluate a biased sampling issue associated with genome-wide association analysis (GWAS) of imaging phenotypes for most imaging genetic studies, including the Alzheimer's Disease Neuroimaging Initiative (ADNI). Specifically, the original sampling scheme of these imaging genetic studies is primarily the retrospective case-control design, whereas most existing statistical analyses of these studies ignore such sampling scheme by directly correlating imaging phenotypes (called the secondary traits) with genotype. Although it has been well documented in genetic epidemiology that ignoring the case-control sampling scheme can produce highly biased estimates, and subsequently lead to misleading results and suspicious associations, such findings are not well documented in imaging genetics. We use extensive simulations and a large-scale imaging genetic data analysis of the Alzheimer's Disease Neuroimaging Initiative (ADNI) data to evaluate the effects of the case-control sampling scheme on GWAS results based on some standard statistical methods, such as linear regression methods, while comparing it with several advanced statistical methods that appropriately adjust for the case-control sampling scheme. Copyright © 2016 Elsevier Inc. All rights reserved.

In Parkinson's disease STN stimulation enhances responsiveness of movement initiation speed to high reward value.

PubMed

Kojovic, Maja; Higgins, Andrea; Jahanshahi, Marjan

2016-08-01

The subthalamic nucleus (STN) is part of the motor, associative, and limbic cortico-striatal circuits through which it can influence a range of behaviours, with preclinical and clinical evidence suggesting that the STN is involved in motivational modulation of behaviour. In the present study, we investigated if in Parkinson's disease (PD) motivational modulation of movement speed is altered by deep brain stimulation (DBS) of the STN (STN-DBS). We studied the effect of monetary incentive on speed of movement initiation and execution in a computer-based simple reaction time task in 10 operated patients with Parkinson's disease using a STN DBS ON/OFF design and also in 11 healthy participants. Prospect of reward improved speed of movement initiation in PD patients both with STN-DBS ON and OFF. However, only with STN-DBS ON, the patients showed greater speeding of initiation time with higher reward magnitude, suggesting enhanced responsivity to higher reward value. Also, on the rewarded trials, PD patients ON stimulation made more anticipation errors than on unrewarded trials, reflecting a propensity to impulsive responses triggered by prospect of reward by subthalamic stimulation. The motivational modulation of movement speed was preserved and enhanced in PD with STN-DBS. Motivational modulation of movement speed in PD is maintained with STN-DBS, with STN stimulation having a further energizing effect on movement initiation in response to greater incentive value. Our results suggest that STN plays a role in integrating motivational influences into motor action, which may explain some previous reports of STN-DBS induced impulsivity with increased motivational salience of stimuli. Copyright © 2016. Published by Elsevier Ltd.

Multivariate Protein Signatures of Pre-Clinical Alzheimer's Disease in the Alzheimer's Disease Neuroimaging Initiative (ADNI) Plasma Proteome Dataset

PubMed Central

Johnstone, Daniel; Milward, Elizabeth A.; Berretta, Regina; Moscato, Pablo

2012-01-01

Background Recent Alzheimer's disease (AD) research has focused on finding biomarkers to identify disease at the pre-clinical stage of mild cognitive impairment (MCI), allowing treatment to be initiated before irreversible damage occurs. Many studies have examined brain imaging or cerebrospinal fluid but there is also growing interest in blood biomarkers. The Alzheimer's Disease Neuroimaging Initiative (ADNI) has generated data on 190 plasma analytes in 566 individuals with MCI, AD or normal cognition. We conducted independent analyses of this dataset to identify plasma protein signatures predicting pre-clinical AD. Methods and Findings We focused on identifying signatures that discriminate cognitively normal controls (n = 54) from individuals with MCI who subsequently progress to AD (n = 163). Based on p value, apolipoprotein E (APOE) showed the strongest difference between these groups (p = 2.3×10−13). We applied a multivariate approach based on combinatorial optimization ((α,β)-k Feature Set Selection), which retains information about individual participants and maintains the context of interrelationships between different analytes, to identify the optimal set of analytes (signature) to discriminate these two groups. We identified 11-analyte signatures achieving values of sensitivity and specificity between 65% and 86% for both MCI and AD groups, depending on whether APOE was included and other factors. Classification accuracy was improved by considering “meta-features,” representing the difference in relative abundance of two analytes, with an 8-meta-feature signature consistently achieving sensitivity and specificity both over 85%. Generating signatures based on longitudinal rather than cross-sectional data further improved classification accuracy, returning sensitivities and specificities of approximately 90%. Conclusions Applying these novel analysis approaches to the powerful and well-characterized ADNI dataset has identified sets of

Dietary patterns are associated with disease risk among participants in the women's health initiative observational study

USDA-ARS?s Scientific Manuscript database

Coronary heart disease (CHD) is the leading cause of death in women. A nested case-control study tested whether dietary patterns predicted CHD events among 1224 participants in the Women’s Health Initiative-Observational Study (WHI-OS) with centrally confirmed CHD, fatal or nonfatal myocardial infar...

Quality of care in patients with psoriasis: an initial clinical study of an international disease management programme.

PubMed

de Korte, J; Van Onselen, J; Kownacki, S; Sprangers, M A G; Bos, J D

2005-01-01

Patients with psoriasis have to cope with their disease for many years or even throughout their entire life. To provide optimal care, a disease management programme was developed. This programme consisted of disease education, disease management training, and psychological support, together with topical treatment. To test a disease management programme in dermatological practice, to assess patients' satisfaction with this programme, and adherence to topical treatment. Additionally, disease severity and quality of life were assessed. An initial clinical investigation was conducted in 10 European treatment centres. A total of 330 patients were included. Patient satisfaction, adherence, disease severity and quality of life were measured with study-specific and standardized self-report questionnaires. Patients reported a high degree of satisfaction with the programme, and a high degree of adherence to topical treatment. Disease severity and quality of life significantly improved. The programme was well received by the participating professionals. The disease management programme was found to be a useful tool in the management of psoriasis, providing patients with relief from the burden of psoriasis in everyday life. A full-scale evaluation is recommended.

The Alzheimer’s Disease Neuroimaging Initiative: Progress report and future plans

PubMed Central

Weiner, Michael W.; Aisen, Paul S.; Jack, Clifford R.; Jagust, William J.; Trojanowski, John Q.; Shaw, Leslie; Saykin, Andrew J.; Morris, John C.; Cairns, Nigel; Beckett, Laurel A.; Toga, Arthur; Green, Robert; Walter, Sarah; Soares, Holly; Snyder, Peter; Siemers, Eric; Potter, William; Cole, Patricia E.; Schmidt, Mark

2010-01-01

The Alzheimer’s Disease Neuroimaging Initiative (ADNI) beginning in October 2004, is a 6-year re-search project that studies changes of cognition, function, brain structure and function, and biomarkers in elderly controls, subjects with mild cognitive impairment, and subjects with Alzheimer’s disease (AD). A major goal is to determine and validate MRI, PET images, and cerebrospinal fluid (CSF)/blood biomarkers as predictors and outcomes for use in clinical trials of AD treatments. Structural MRI, FDG PET, C-11 Pittsburgh compound B (PIB) PET, CSF measurements of amyloid β (Aβ) and species of tau, with clinical/cognitive measurements were performed on elderly controls, subjects with mild cognitive impairment, and subjects with AD. Structural MRI shows high rates of brain atrophy, and has high statistical power for determining treatment effects. FDG PET, C-11 Pittsburgh compound B PET, and CSF measurements of Aβ and tau were significant predictors of cognitive decline and brain atrophy. All data are available at UCLA/LONI/ADNI, without embargo. ADNI-like projects started in Australia, Europe, Japan, and Korea. ADNI provides significant new information concerning the progression of AD. PMID:20451868

Changes in co-therapies after initiation of disease-modifying anti-rheumatic drugs (DMARDs) therapy in patients with rheumatoid arthritis

PubMed Central

Kawai, Vivian K.; Grijalva, Carlos G.; Arbogast, Patrick G.; Curtis, Jeffrey R.; Solomon, Daniel H.; Delzell, Elizabeth; Chen, Lang; Ouellet-Hellstrom, Rita; Herrinton, Lisa; Liu, Liyan; Mitchell, Edward F.; Stein, C. Michael; Griffin, Marie R.

2011-01-01

Objectives We hypothesized that initiation of a new disease modifying anti-rheumatic drug DMARD) for rheumatoid arthritis (RA) treatment would decrease use of corticosteroids, nonsteroidal anti-inflammatory drugs (NSAIDs) and narcotics. Methods Using administrative databases we assembled 4 retrospective cohorts of RA patients (1998-2005), and identified 5 groups initiating DMARD regimens: methotrexate with (new MTX) or without (first MTX) use of other non-biologic DMARDs in the previous year; new hydroxychloroquine and/or sulfasalazine (new HCQ/SSZ) and new leflunomide (new LEF), both with previous use of MTX; and new TNF-α antagonists (new anti-TNF). We compared within-person differences in any use of co-therapies (≥1 prescription) between the 6 months before and the 6-12 months after DMARD initiation. Results Among 32476 DMARD initiators, the prevalence of corticosteroids, NSAIDs and narcotics use increased by 15%, 5% and 6% respectively in the 6 months before initiation compared to the previous 6 months suggesting worsening of the disease. In the 6 to 12 months after initiation for most initiator groups, more patients stopped using corticosteroids and NSAIDs than started, with overall decreases of 8.9% [95%CI 8.4-9.4%] for corticosteroids and 12.9% [95%CI 12.3-13.4%] for NSAIDs. The proportion of narcotic users changed little (overall decrease of 2.5% [95%CI 1.9-3.0%]). Conclusions Use of all three co-therapies increased in the 6 months before initiation of new DMARD regimens for RA. Use of corticosteroids and NSAIDs decreased modestly 6-12 months fter initiation, but there was only a very small decrease in narcotic use. These differential changes require further study. PMID:22121511

The harmless acute pancreatitis score: a clinical algorithm for rapid initial stratification of nonsevere disease.

PubMed

Lankisch, Paul Georg; Weber-Dany, Bettina; Hebel, Kathrin; Maisonneuve, Patrick; Lowenfels, Albert B

2009-06-01

Only severe acute pancreatitis requires treatment, according to the principles of intensive care medicine in an intensive care or intermediate care unit. The aim of the study was to define and evaluate a simple clinical algorithm for rapid initial identification of patients with a first attack of acute pancreatitis who do not require intensive care. This prospective study included 394 patients who were admitted to the Municipal Clinic of Lüneburg, Germany, between 1987 and 2003. From a number of parameters of disease severity on admission, 3 parameters that showed the strongest prediction of a nonsevere course (no rebound tenderness and/or guarding, normal hematocrit level, and normal serum creatinine level) were combined to form the harmless acute pancreatitis score (HAPS). The score then was validated in a German multicenter study including 452 patients between 2004 and 2006. In both the initial and the validation set, the HAPS correlated with a nonsevere course of the disease (P < .0001). The score correctly identified a harmless course in 200 (98%) of 204 patients. The HAPS enables identification, within approximately 30 minutes after admission, of patients with acute pancreatitis whose disease will run a mild course. The high level of accuracy of this test (98%) will allow physicians to identify patients quickly who do not require intensive care, and potentially those who will not require inpatient treatment at all. Thus, the HAPS may save substantial hospital costs.

Development and initial validation of the assessment of caregiver experience with neuromuscular disease.

PubMed

Matsumoto, Hiroko; Clayton-Krasinski, Debora A; Klinge, Stephen A; Gomez, Jaime A; Booker, Whitney A; Hyman, Joshua E; Roye, David P; Vitale, Michael G

2011-01-01

Orthopaedic intervention can have a wide range of functional and psychosocial effects on children with neuromuscular disease (NMD). In the multihandicapped child (Gross Motor Classification System IV/V), functional status, pain, psychosocial function, and health-related quality of life also have effects on the families of these child. The purpose of this study is to report the development and initial validation of an outcomes instrument specifically designed to assess the caregiver impact experienced by parents raising severely affected NMD children: the Assessment of Caregiver Experience with Neuromuscular Disease (ACEND). In the first part of this prospective study, 61 children with NMD and their parents were administered a range of earlier validated pediatric health measures. A framework technique was used to select the most appropriate and relevant subset of questions from this large set. Sensitivity analyses guided the development of a master question list measuring caregiver impact, excluding items with low relevance, and modifying unclear questions. In the second part of the study, the ACEND was administered to the caregivers of 46 children with moderate-to-severe NMD. Statistical analyses were conducted to determine validity of the instrument. The resulting ACEND instrument included 2 domains, 7 subdomains, and 41 items. Domain 1, examining physical impact, includes 4 subdomains: feeding/grooming/dressing (6 items), sitting/play (5 items), transfers (5 items), and mobility (7 items). Domain 2, which examines general caregiver impact, included 3 subdomains: time (4 items), emotion (9 items), and finance (5 items). Mean overall relevance rating was 6.21 ± 0.37 and clarity rating was 6.68 ± 0.52 (scale 0 to 7). Multiple floor effects in patients with GMFCS V and ceiling effects in patients with GMFCS III were identified almost exclusively in motor-based items. Virtually no floor or ceiling effects were identified in the time, emotion or finance domains

The Alzheimer's Disease Neuroimaging Initiative 2 PET Core: 2015.

PubMed

Jagust, William J; Landau, Susan M; Koeppe, Robert A; Reiman, Eric M; Chen, Kewei; Mathis, Chester A; Price, Julie C; Foster, Norman L; Wang, Angela Y

2015-07-01

This article reviews the work done in the Alzheimer's Disease Neuroimaging Initiative positron emission tomography (ADNI PET) core over the past 5 years, largely concerning techniques, methods, and results related to amyloid imaging in ADNI. The PET Core has used [(18)F]florbetapir routinely on ADNI participants, with over 1600 scans available for download. Four different laboratories are involved in data analysis, and have examined factors such as longitudinal florbetapir analysis, use of [(18)F]fluorodeoxyglucose (FDG)-PET in clinical trials, and relationships between different biomarkers and cognition. Converging evidence from the PET Core has indicated that cross-sectional and longitudinal florbetapir analyses require different reference regions. Studies have also examined the relationship between florbetapir data obtained immediately after injection, which reflects perfusion, and FDG-PET results. Finally, standardization has included the translation of florbetapir PET data to a centiloid scale. The PET Core has demonstrated a variety of methods for the standardization of biomarkers such as florbetapir PET in a multicenter setting. Copyright © 2015 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.

The impact of birth weight on cardiovascular disease risk in the Women's Health Initiative

PubMed Central

Smith, CJ; Ryckman, KK; Barnabei, Vanessa M.; Howard, Barbara; Isasi, Carmen R.; Sarto, Gloria; Tom, Sarah E.; Van Horn, Linda; Wallace, Robert; Robinson, Jennifer G

2016-01-01

Background and Aims Cardiovascular disease (CVD) is among the leading causes of morbidity and mortality worldwide. Traditional risk factors predict 75-80% of an individual's risk of incident CVD. However, the role of early life experiences in future disease risk is gaining attention. The Barker hypothesis proposes fetal origins of adult disease, with consistent evidence demonstrating the deleterious consequences of birth weight outside the normal range. In this study, we investigate the role of birth weight in CVD risk prediction. Methods and Results The Women's Health Initiative (WHI) represents a large national cohort of post-menopausal women with 63 815 participants included in this analysis. Univariable proportional hazards regression analyses evaluated the association of 4 self-reported birth weight categories against 3 CVD outcome definitions, which included indicators of coronary heart disease, ischemic stroke, coronary revascularization, carotid artery disease and peripheral arterial disease. The role of birth weight was also evaluated for prediction of CVD events in the presence of traditional risk factors using 3 existing CVD risk prediction equations: one body mass index (BMI)-based and two laboratory-based models. Low birth weight (LBW) (< 6 lbs.) was significantly associated with all CVD outcome definitions in univariable analyses (HR=1.086, p=0.009). LBW was a significant covariate in the BMI-based model (HR=1.128, p<0.0001) but not in the lipid-based models. Conclusion LBW (<6 lbs.) is independently associated with CVD outcomes in the WHI cohort. This finding supports the role of the prenatal and postnatal environment in contributing to the development of adult chronic disease. PMID:26708645

The Alzheimer’s Disease Neuroimaging Initiative 2 Biomarker Core: A review of progress and plans

PubMed Central

Kang, Ju-Hee; Korecka, Magdalena; Figurski, Michal J.; Toledo, Jon B.; Blennow, Kaj; Zetterberg, Henrik; Waligorska, Teresa; Brylska, Magdalena; Fields, Leona; Shah, Nirali; Soares, Holly; Dean, Robert A.; Vanderstichele, Hugo; Petersen, Ronald C.; Aisen, Paul S.; Saykin, Andrew J.; Weiner, Michael W.; Trojanowski, John Q.; Shaw, Leslie M.

2016-01-01

Introduction We describe Alzheimer’s Disease Neuroimaging Initiative (ADNI) Biomarker Core progress including: the Biobank; cerebrospinal fluid (CSF) amyloid beta (Aβ1–42), t-tau, and p-tau181 analytical performance, definition of Alzheimer’s disease (AD) profile for plaque, and tangle burden detection and increased risk for progression to AD; AD disease heterogeneity; progress in standardization; and new studies using ADNI biofluids. Methods Review publications authored or coauthored by ADNI Biomarker core faculty and selected non-ADNI studies to deepen the understanding and interpretation of CSF Aβ1–42, t-tau, and p-tau181 data. Results CSFAD biomarker measurements with the qualified AlzBio3 immunoassay detects neuropathologic AD hallmarks in preclinical and prodromal disease stages, based on CSF studies in non-ADNI living subjects followed by the autopsy confirmation of AD. Collaboration across ADNI cores generated the temporal ordering model of AD biomarkers varying across individuals because of genetic/environmental factors that increase/decrease resilience to AD pathologies. Discussion Further studies will refine this model and enable the use of biomarkers studied in ADNI clinically and in disease-modifying therapeutic trials. PMID:26194312

Pharmacogenetics during standardised initiation of thiopurine treatment in inflammatory bowel disease

PubMed Central

Hindorf, U; Lindqvist, M; Peterson, C; Söderkvist, P; Ström, M; Hjortswang, H; Pousette, A; Almer, S

2006-01-01

Background Firm recommendations about the way thiopurine drugs are introduced and the use of thiopurine methyltransferase (TPMT) and metabolite measurements during treatment in inflammatory bowel disease (IBD) are lacking. Aim To evaluate pharmacokinetics and tolerance after initiation of thiopurine treatment with a fixed dosing schedule in patients with IBD. Patients 60 consecutive patients with Crohn's disease (n = 33) or ulcerative colitis (n = 27) were included in a 20 week open, prospective study. Methods Thiopurine treatment was introduced using a predefined dose escalation schedule, reaching a daily target dose at week 3 of 2.5 mg azathioprine or 1.25 mg 6‐mercaptopurine per kg body weight. TPMT and ITPA genotypes, TPMT activity, TPMT gene expression, and thiopurine metabolites were determined. Clinical outcome and occurrence of adverse events were monitored. Results 27 patients completed the study per protocol, while 33 were withdrawn (early protocol violation (n = 5), TPMT deficiency (n = 1), thiopurine related adverse events (n = 27)); 67% of patients with adverse events tolerated long term treatment on a lower dose (median 1.32 mg azathioprine/kg body weight). TPMT activity did not change during the 20 week course of the study but a significant decrease in TPMT gene expression was found (TPMT/huCYC ratio; p = 0.02). Patients with meTIMP concentrations >11 450 pmol/8×108 red blood cells during steady state at week 5 had an increased risk of developing myelotoxicity (odds ratio = 45.0; p = 0.015). Conclusions After initiation of thiopurine treatment using a fixed dosing schedule, no general induction of TPMT enzyme activity occurred, though TPMT gene expression decreased. The development of different types of toxicity was unpredictable, but we found that measurement of meTIMP early in the steady state phase helped to identify patients at risk of developing myelotoxicity. PMID:16543290

Ethnoracial Differences in the Clinical Characteristics of Alzheimer Disease at Initial Presentation at an Urban Alzheimer’s Disease Center

PubMed Central

Livney, Melissa Gartenberg; Clark, Christopher M.; Karlawish, Jason H.; Cartmell, Su; Negrón, Mirna; Nuñez-Lopez, Jessica; Xie, Sharon X.; Entenza-Cabrera, Fernando; Vega, Irving E.; Arnold, Steven E.

2010-01-01

Objective To compare presentation of Alzheimer disease (AD) at the time of initial evaluation at a university specialty clinic across three ethnoracial groups in order to understand similarities and differences in the demographic, clinical, cognitive, psychiatric, and biologic features. Design Cross-sectional study. Participants A total of 1,341 self-identified African American, Latino (primarily of Caribbean origin), and white non-Hispanic (“WNH”) subjects were recruited from primary care sites or by referral by primary care physicians. Measurements Demographic variables and age of onset of AD, as well as cognitive, functional, and mood impairments at the time of initial presentation and frequencies of apolipoprotein E genotypes, were compared across groups. Results Differences among ethnoracial groups were found for nearly all variables of interest. In particular, the largely immigrant Puerto Rican Latino group had an earlier age of onset of AD, more cognitive impairment, and greater severity of cognitive impairment at the time of initial evaluation in the setting of low average education and socioeconomic status. There was more depression in the Latinos compared with African Americans and WNHs. Greater severity of symptoms was not accounted for by a difference in lag time between onset of symptoms and initial evaluation. The apolipoprotein E-4 genotype was not associated with AD in the Latino cohort. Conclusions Minority groups in Philadelphia, especially Latinos, exhibit a more severe profile of AD at the time of presentation than WNHs. Important potential confounds need to be considered and future research comparing immigrant and nonimmigrant Latino groups will be necessary to elucidate the highly significant differences reported. PMID:21522051

Endothelin A receptor activation on mesangial cells initiates Alport glomerular disease

PubMed Central

Dufek, Brianna; Meehan, Daniel; Delimont, Duane; Cheung, Linda; Gratton, Michael Anne; Phillips, Grady; Song, Wenping; Liu, Shiguang; Cosgrove, Dominic

2016-01-01

Recent work demonstrates that Alport glomerular disease is mediated through a biomechanical strain-sensitive activation of mesangial actin dynamics. This occurs through a Rac1/CDC42 cross-talk mechanism that results in the invasion of the sub-capillary spaces by mesangial filopodia. The filopodia deposit mesangial matrix proteins in the glomerular basement membrane, including laminin 211, which activates focal adhesion kinase in podocytes culminating in the up-regulation of pro-inflammatory cytokines and metalloproteinases. These events drive the progression of glomerulonephritis. Here we test whether endothelial cell-derived endothelin-1 is upregulated in Alport glomeruli, and further elevated by hypertension. Treatment of cultured mesangial cells with endothelin-1 activates the formation of drebrin-positive actin microspikes. These microspikes do not form when cells are treated with the endothelin A receptor antagonist sitaxentan, or under conditions of siRNA knockdown of endothelin A receptor mRNA. Treatment of Alport mice with sitaxentan results in delayed onset of proteinuria, normalized glomerular basement membrane morphology, inhibition of mesangial filopodial invasion of the glomerular capillaries, normalization of glomerular expression of metalloproteinases and pro-inflammatory cytokines, increased lifespan, and prevention of glomerulosclerosis and interstitial fibrosis. Thus endothelin A receptor activation on mesangial cells is a key event in initiation of Alport glomerular disease in this model. PMID:27165837

Multiple bidirectional initiations and terminations of transcription in the Marek's disease virus long repeat regions.

PubMed Central

Chen, X B; Velicer, L F

1991-01-01

Marek's disease is an oncogenic disease of chickens caused by a herpesvirus, Marek's disease virus (MDV). Serial in vitro passage of pathogenic MDV results in amplification of a 132-bp direct repeat in the MDV genome's TRL and IRL repeat regions and loss of tumorigenicity. This led to the hypothesis that upon such expansion, one or more tumor-inducing genes fail to be expressed. In this report a group of cDNAs mapping in the expanded regions were isolated from a pathogenic MDV strain in which the 132-bp direct repeat number was found to range between one and seven. Partial cDNA sequencing and S1 nuclease protection analysis revealed that the corresponding transcripts are either initiated or terminated within or near the expanded regions at multiple sites in both rightward and leftward directions. Furthermore, each 132-bp repeat contains one TATA box and two polyadenylation consensus sequences in each direction. These RNAs contain a partial copy or one or more full copies of the 132-bp direct repeat at either their 5' or 3' end. Northern (RNA) blot analysis showed that the majority of transcripts are 1.8 kb in size, while the minor species range in size from 0.67 to 3.1 kb. Together, these data raise the possibility that the 132-bp direct repeat, and indirectly its copy number, may be involved in the regulation of transcriptional initiation and termination and therefore in the generation of four groups of transcripts from the TRL and IRL, although this remains to be demonstrated. Images PMID:1850022

African goat improvement project: A feed the future initiative harnessing geneticdiversity for conservation, disease resistance, and improved productivity

USDA-ARS?s Scientific Manuscript database

AFRICAN GOAT IMPROVEMENT PROJECT: A FEED THE FUTURE INITIATIVE HARNESSING GENETIC DIVERSITY FOR CONSERVATION, DISEASE RESISTANCE, AND IMPROVED PRODUCTIVITY Food production systems in Africa depend heavily on the use of locally adapted animals. These animals are of agricultural, cultural, and econom...

Pulmonary involvement in Fabry disease: effect of plasma globotriaosylsphingosine and time to initiation of enzyme replacement therapy.

PubMed

Franzen, Daniel; Haile, Sarah R; Kasper, David C; Mechtler, Thomas P; Flammer, Andreas J; Krayenbühl, Pierre A; Nowak, Albina

2018-01-01

Anderson-Fabry disease (AFD) is an X-linked lysosomal storage disorder caused by mutations of GLA gene leading to reduced α-galactosidase activity and resulting in a progressive accumulation of globotriaosylceramide (Gb3) and its deacylated derivative, globotriaosyl-sphingosine (Lyso-Gb3). Plasma Lyso-Gb3 levels serve as a disease severity and treatment monitoring marker during enzyme replacement therapy (ERT). Adult patients with AFD who had yearly pulmonary function tests between 1999 and 2015 were eligible for this observational study. Primary outcome measures were the change in z-score of forced expiratory volume in the first second (FEV 1 ) and FEV 1 /FVC over time. Plasma Lyso-Gb3 levels and the age of ERT initiation were investigated for their association with lung function decline. Fifty-three patients (42% male, median (range) age at diagnosis of AFD 34 (6-61) years in men, 34 (13-67) in women) were included. The greatest decrease of FEV 1 /FVC z-scores was observed in Classic men (-0.048 per year, 95% CI -0.081 to -0.014), compared with the Later-Onset men (+0.013,95% CI -0.055 to 0.082), Classic women (-0.008, 95% CI -0.035 to +0.020) and Later-Onset women (-0.013, 95% CI -0.084 to +0.058). Cigarette smoking (P=0.022) and late ERT initiation (P=0.041) were independently associated with faster FEV 1 decline. FEV 1 /FVC z-score decrease was significantly reduced after initiation of ERT initiation (-0.045 compared with -0.015, P=0.014). Furthermore, there was a trend towards a relevant influence of Lyso-Gb3 (P=0.098) on airflow limitation with age. Early ERT initiation seems to preserve pulmonary function. Plasma Lyso-Gb3 is maybe a useful predictor for airflow limitation. Classic men need a closer monitoring of the lung function.

Controversies in neurology: why monoamine oxidase B inhibitors could be a good choice for the initial treatment of Parkinson's disease.

PubMed

Löhle, Matthias; Reichmann, Heinz

2011-09-22

Early initiation of pharmacotherapy in Parkinson's disease (PD) is nowadays widely advocated by experts since the delay of treatment has shown to be associated with a significant deterioration of health related quality of life in affected patients. Due to marked advances in PD treatment during the last decades, physicians are nowadays fortunately equipped with a variety of substances that can effectively ameliorate emerging motor symptoms of the disease, among them levodopa, dopamine agonists and monoamine oxidase type B (MAO-B) inhibitors. Despite numerous drug intervention trials in early PD, there is however still ongoing controversy among neurologists which substance to use for the initial treatment of the disease. In multiple studies, MAO-B inhibitors, such as selegiline and rasagiline, have shown to provide mild symptomatic effects, delay the need for levodopa, and to reduce the incidence of motor fluctuations. Although their symptomatic efficacy is inferior compared to dopamine agonists and levodopa, MAO-B inhibitors undoubtedly have fewer side effects and are easy to administer. In contrary to their competitors, MAO-B inhibitors may furthermore offer a chance for disease modification, which so far remains a major unmet need in the management of PD and eventually makes them ideal candidates for the early treatment of the disease. MAO-B inhibitors may constitute a preferable therapeutic option for early PD, mainly due to their favourable safety profile and their putative neuroprotective capabilities. Since the symptomatic effects of MAO-B inhibitors are comparatively mild, dopamine agonists and levodopa should however be considered for initial treatment in those PD patients, in whom robust and immediate symptomatic relief needs to be prioritized.

Initiation of reflective frames in counseling for Huntingtons Disease predictive testing.

PubMed

Sarangi, Srikant; Bennert, Kristina; Howell, Lucy; Clarke, Angus; Harper, Peter; Gray, Jonathon

2004-04-01

Genetic professionals and clients are likely to assign different meanings to the extended format of the counseling protocols for predictive testing. In order to facilitate informed, client-centered decisions about the possibility of predictive testing, counselors routinely use the question format to initiate what we call "reflective frames" that invite clients to discuss their feelings and encourage them to adopt introspective and self-reflective stances toward their own experience--spanning the past, the present, and the hypothetical future. We suggest that such initiations of reflective frames constitute a key element of counselors' nondirective stance, although the exact nature of their formulations can be complex and varied. Examining 24 Huntington's Disease (HD) clinic sessions involving 12 families in South Wales with the tools of discourse analysis, our focus in this paper is twofold: (i) to propose a classification of six types of reflective questions (e.g. nonspecific invites, awareness and anxiety, decision about testing, impact of result, dissemination, and other) and to examine their distribution across the various clinic appointments, and (ii) to investigate the scope of these questions in terms of temporal and social axes. We link our analysis to the current debate within the genetic counseling profession about the merits of reflection- versus information-focused counseling styles and the need to abide by professionally warranted and institutionally embedded counseling protocols.

Matriptase initiates epidermal prokallikrein activation and disease onset in a mouse model of Netherton syndrome

PubMed Central

Sales, Katiuchia Uzzun; Masedunskas, Andrius; Bey, Alexandra L.; Rasmussen, Amber; Weigert, Roberto; List, Karin; Szabo, Roman; Overbeek, Paul A.; Bugge, Thomas H.

2010-01-01

Deficiency in the serine protease inhibitor LEKTI is the etiological origin of Netherton syndrome. The principal morbidities of the disease are stratum corneum detachment and chronic inflammation. We show that the membrane protease, matriptase, initiates Netherton syndrome in a LEKTI-deficient mouse model by premature activation of a pro-kallikrein-related cascade. Auto-activation of pro-inflammatory and stratum corneum detachment-associated pro-kallikrein-related peptidases was either low or undetectable, but they were efficiently activated by matriptase. Ablation of matriptase from LEKTI-deficient mice dampened inflammation, eliminated aberrant protease activity, prevented stratum corneum detachment, and improved epidermal barrier function. The study uncovers a pathogenic matriptase-pro-kallikrein pathway that could be operative in several human skin and inflammatory diseases. PMID:20657595

Novel mutation identified in severe early-onset tumor necrosis factor receptor-associated periodic syndrome: a case report.

PubMed

Radhakrishna, Suhas M; Grimm, Amy; Broderick, Lori

2017-04-20

Tumor Necrosis Factor Receptor-Associated Periodic Syndrome (TRAPS) is the second most common heritable autoinflammatory disease, typically presenting in pre-school aged children with fever episodes lasting 1-3 weeks. Systemic symptoms can include rash, myalgia, ocular inflammation, and serositis. Here we report an unusual presentation of TRAPS in a 7 month old girl who presented with only persistent fever. She was initially diagnosed with incomplete Kawasaki Disease and received IVIG and infliximab; however, her fevers quickly recurred. Subsequent testing revealed a urinary tract infection, but she did not improve despite appropriate therapy. As fever continued, she developed significant abdominal distension with imaging concerning for appendicitis, followed by hyperthermia and hemodynamic instability. Given her protracted clinical course and maternal history of a poorly defined inflammatory condition, an autoinflammatory disease was considered. Therapy with anakinra was initiated, resulting in rapid resolution of fever and normalization of inflammatory markers. She was found to have a previously unreported mutation, Thr90Pro, in the TNFRSF1A gene associated with TRAPS. This novel mutation was also confirmed in the patient's mother and maternal uncle. This report reviews a severe case of TRAPS in infancy associated with a novel mutation, Thr90Pro, in the TNFRSF1A gene, and emphasizes that autoinflammatory disease should be considered in the differential of infants with fever of unknown origin.

[Treatment and outcome of Crohn's disease without initial complications. Results of a retrospective, multicenter Tunisian study].

PubMed

Cheikh, Imed; Ben Ammar, Ahmed; Essid, Mejda; Azzouz, Messadak; Ettahri, Nabil; Krichene, Mohamed; Bouzaidi, Slim; Ennajar, Taoufik

2002-04-01

The purpose of this study was to estimate and achieve the factors that have an influence on the evolution of the Chron's disease. This study was done in 124 patients reaching the diagnosis of Chron's disease between 1988 and 1997. The evolution of this disease was achieved in 87 patients. The Chron's disease was inactive among 31 patients (35-6%)--with discontinous evolution in 42 patients (48.3%) and active chronic in 14 patients (16-1%). The active chronic form of Chron's disease was twice more frequent among the smokers and the patients with age above 40 years--but this difference has no statistical significance. The indication of surgical treatment was realised in 21 patients and it takes place as result of failure of medical treatment in 16 patients (76-2%)--an abcess in 2 patents (9-5%) and iatrogenic perforation in 1 patient (4-8%). The age-sexe-smoke--the intensity of the initial attack and the nature of the treatment had no influence in the need of the surgical interfference. The Chron's disease showed the less severe evolution in this study--the age above 40 years and the consumption of smoke increased the frequency of active chronic form.

Towards reframing health service delivery in Uganda: the Uganda Initiative for Integrated Management of Non-Communicable Diseases.

PubMed

Schwartz, Jeremy I; Dunkle, Ashley; Akiteng, Ann R; Birabwa-Male, Doreen; Kagimu, Richard; Mondo, Charles K; Mutungi, Gerald; Rabin, Tracy L; Skonieczny, Michael; Sykes, Jamila; Mayanja-Kizza, Harriet

2015-01-01

The burden of non-communicable diseases (NCDs) in low- and middle-income countries (LMICs) is accelerating. Given that the capacity of health systems in LMICs is already strained by the weight of communicable diseases, these countries find themselves facing a double burden of disease. NCDs contribute significantly to morbidity and mortality, thereby playing a major role in the cycle of poverty, and impeding development. Integrated approaches to health service delivery and healthcare worker (HCW) training will be necessary in order to successfully combat the great challenge posed by NCDs. In 2013, we formed the Uganda Initiative for Integrated Management of NCDs (UINCD), a multidisciplinary research collaboration that aims to present a systems approach to integrated management of chronic disease prevention, care, and the training of HCWs. Through broad-based stakeholder engagement, catalytic partnerships, and a collective vision, UINCD is working to reframe integrated health service delivery in Uganda.

Clinical benefit of continuing crizotinib therapy after initial disease progression in Chinese patients with advanced ALK-rearranged non-small-cell lung cancer

PubMed Central

Hong, Xiangchan; Chen, Qi; Ding, Lingyu; Liang, Ying; Zhou, Ningning; Fang, Wenfeng; Chen, Xinru; Wu, Haiying

2017-01-01

Purpose Although most patients with ALK-positive non?small-cell lung cancer (NSCLC) who benefit from treatment with crizotinib ultimately develop progressive disease (PD), continuing crizotinb beyond the initial PD (CBPD) in these patients may be beneficial. In this study, we investigated whether Chinese patients with advanced ALK-positive NSCLC benefit from CBPD, and whether any factors are predictive of a longer post-initial progression-free survival time (PFS2). Materials and Methods Data on 33 patients with ALK-positive NSCLC who achieved disease control with crizotinib were analyzed retrospectively. The impact of continued crizotinib therapy on the patients’ PFS2 time was assessed after adjusting for potential confounding factors. Results With initial crizotinib therapy, the objective response rate (ORR) and median PFS time (PFS1) in the 33 patients were 63.6% and 8.6 months, respectively. With continued crizotinib therapy after documentation of PD, the median PFS2 for all 33 patients was 16 weeks, and in those with CNS progression but systemic disease control it was 30 weeks. Patients who received local therapy after disease progression had a significantly longer PFS2 compared with those who did not (P = 0.039). Multivariable Cox regression analysis showed that the PFS1 with initial crizotinib treatment and local therapy were independent predictors of PFS2. Discussion This study provides further evidence of the benefit of continuing crizotinib therapy in Chinese patients with progressive ALK-positive NSCLC. Patients with a longer PFS1 and those who received local brain therapy would have a longer period of continuing crizotinib. PMID:28427213

Clinical benefit of continuing crizotinib therapy after initial disease progression in Chinese patients with advanced ALK-rearranged non-small-cell lung cancer.

PubMed

Hong, Xiangchan; Chen, Qi; Ding, Lingyu; Liang, Ying; Zhou, Ningning; Fang, Wenfeng; Chen, Xinru; Wu, Haiying

2017-06-20

Although most patients with ALK-positive non-small-cell lung cancer (NSCLC) who benefit from treatment with crizotinib ultimately develop progressive disease (PD), continuing crizotinb beyond the initial PD (CBPD) in these patients may be beneficial. In this study, we investigated whether Chinese patients with advanced ALK-positive NSCLC benefit from CBPD, and whether any factors are predictive of a longer post-initial progression-free survival time (PFS2). Data on 33 patients with ALK-positive NSCLC who achieved disease control with crizotinib were analyzed retrospectively. The impact of continued crizotinib therapy on the patients' PFS2 time was assessed after adjusting for potential confounding factors. With initial crizotinib therapy, the objective response rate (ORR) and median PFS time (PFS1) in the 33 patients were 63.6% and 8.6 months, respectively. With continued crizotinib therapy after documentation of PD, the median PFS2 for all 33 patients was 16 weeks, and in those with CNS progression but systemic disease control it was 30 weeks. Patients who received local therapy after disease progression had a significantly longer PFS2 compared with those who did not (P = 0.039). Multivariable Cox regression analysis showed that the PFS1 with initial crizotinib treatment and local therapy were independent predictors of PFS2. This study provides further evidence of the benefit of continuing crizotinib therapy in Chinese patients with progressive ALK-positive NSCLC. Patients with a longer PFS1 and those who received local brain therapy would have a longer period of continuing crizotinib.

Tics as an initial manifestation of juvenile Huntington's disease: case report and literature review.

PubMed

Cui, Shi-Shuang; Ren, Ru-Jing; Wang, Ying; Wang, Gang; Chen, Sheng-Di

2017-08-08

Huntington's disease (HD) is an autosomal dominant disorder, typically characterized by chorea due to a trinucleotide repeat expansion in the HTT gene, although the clinical manifestations of patients with juvenile HD (JHD) are atypical. A 17-year-old boy with initial presentation of tics attended our clinic and his DNA analysis demonstrated mutation in the HTT gene (49 CAG repeats). After treatment, his symptoms improved. Furthermore, we performed literature review through searching the databases and summarized clinical features in 33 JHD patients. The most prevalent symptoms are ataxia, and two cases reported that tics as initial and prominent manifestation in JHD. Among them, 88% patients carried CAG repeats beyond 60 and most of them have family history. This case here illustrates the variable range of clinical symptoms of JHD and the necessity of testing for the HD mutation in young patients with tics with symptoms unable to be explained by Tourette's syndrome (TS).

Developing community-driven quality improvement initiatives to enhance chronic disease care in Indigenous communities in Canada: the FORGE AHEAD program protocol.

PubMed

Naqshbandi Hayward, Mariam; Paquette-Warren, Jann; Harris, Stewart B

2016-07-26

Given the dramatic rise and impact of chronic diseases and gaps in care in Indigenous peoples in Canada, a shift from the dominant episodic and responsive healthcare model most common in First Nations communities to one that places emphasis on proactive prevention and chronic disease management is urgently needed. The Transformation of Indigenous Primary Healthcare Delivery (FORGE AHEAD) Program partners with 11 First Nations communities across six provinces in Canada to develop and evaluate community-driven quality improvement (QI) initiatives to enhance chronic disease care. FORGE AHEAD is a 5-year research program (2013-2017) that utilizes a pre-post mixed-methods observational design rooted in participatory research principles to work with communities in developing culturally relevant innovations and improved access to available services. This intensive program incorporates a series of 10 inter-related and progressive program activities designed to foster community-driven initiatives with type 2 diabetes mellitus as the action disease. Preparatory activities include a national community profile survey, best practice and policy literature review, and readiness tool development. Community-level intervention activities include community and clinical readiness consultations, development of a diabetes registry and surveillance system, and QI activities. With a focus on capacity building, all community-level activities are driven by trained community members who champion QI initiatives in their community. Program wrap-up activities include readiness tool validation, cost-analysis and process evaluation. In collaboration with Health Canada and the Aboriginal Diabetes Initiative, scale-up toolkits will be developed in order to build on lessons-learned, tools and methods, and to fuel sustainability and spread of successful innovations. The outcomes of this research program, its related cost and the subsequent policy recommendations, will have the potential to

Motivational Modulation of Self-Initiated and Externally Triggered Movement Speed Induced by Threat of Shock: Experimental Evidence for Paradoxical Kinesis in Parkinson’s Disease

PubMed Central

McDonald, Louise M.; Griffin, Harry J.; Angeli, Aikaterini; Torkamani, Mariam; Georgiev, Dejan; Jahanshahi, Marjan

2015-01-01

Background Paradoxical kinesis has been observed in bradykinetic people with Parkinson’s disease. Paradoxical kinesis occurs in situations where an individual is strongly motivated or influenced by relevant external cues. Our aim was to induce paradoxical kinesis in the laboratory. We tested whether the motivation of avoiding a mild electric shock was sufficient to induce paradoxical kinesis in externally-triggered and self-initiated conditions in people with Parkinson’s disease tested on medication and in age-matched controls. Methods Participants completed a shock avoidance behavioural paradigm in which half of the trials could result in a mild electric shock if the participant did not move fast enough. Half of the trials of each type were self-initiated and half were externally-triggered. The criterion for avoiding shock was a maximum movement time, adjusted according to each participant’s performance on previous trials using a staircase tracking procedure. Results On trials with threat of shock, both patients with Parkinson’s disease and controls had faster movement times compared to no potential shock trials, in both self-initiated and externally-triggered conditions. The magnitude of improvement of movement time from no potential shock to potential shock trials was positively correlated with anxiety ratings. Conclusions When motivated to avoid mild electric shock, patients with Parkinson’s disease, similar to healthy controls, showed significant speeding of movement execution. This was observed in both self-initiated and externally-triggered versions of the task. Nevertheless, in the ET condition the improvement of reaction times induced by motivation to avoid shocks was greater for the PD patients than controls, highlighting the value of external cues for movement initiation in PD patients. The magnitude of improvement from the no potential shock to the potential shock trials was associated with the threat-induced anxiety. This demonstration of

Towards reframing health service delivery in Uganda: the Uganda Initiative for Integrated Management of Non-Communicable Diseases

PubMed Central

Schwartz, Jeremy I.; Dunkle, Ashley; Akiteng, Ann R.; Birabwa-Male, Doreen; Kagimu, Richard; Mondo, Charles K.; Mutungi, Gerald; Rabin, Tracy L.; Skonieczny, Michael; Sykes, Jamila; Mayanja-Kizza, Harriet

2015-01-01

Background The burden of non-communicable diseases (NCDs) in low- and middle-income countries (LMICs) is accelerating. Given that the capacity of health systems in LMICs is already strained by the weight of communicable diseases, these countries find themselves facing a double burden of disease. NCDs contribute significantly to morbidity and mortality, thereby playing a major role in the cycle of poverty, and impeding development. Methods Integrated approaches to health service delivery and healthcare worker (HCW) training will be necessary in order to successfully combat the great challenge posed by NCDs. Results In 2013, we formed the Uganda Initiative for Integrated Management of NCDs (UINCD), a multidisciplinary research collaboration that aims to present a systems approach to integrated management of chronic disease prevention, care, and the training of HCWs. Discussion Through broad-based stakeholder engagement, catalytic partnerships, and a collective vision, UINCD is working to reframe integrated health service delivery in Uganda. PMID:25563451

Perceived Utility of the RE-AIM Framework for Health Promotion/Disease Prevention Initiatives for Older Adults: A Case Study from the U.S. Evidence-Based Disease Prevention Initiative.

PubMed

Ory, Marcia G; Altpeter, Mary; Belza, Basia; Helduser, Janet; Zhang, Chen; Smith, Matthew Lee

2014-01-01

Dissemination and implementation (D&I) frameworks are increasingly being promoted in public health research. However, less is known about their uptake in the field, especially for diverse sets of programs. Limited questionnaires exist to assess the ways that frameworks can be utilized in program planning and evaluation. We present a case study from the United States that describes the implementation of the RE-AIM framework by state aging services providers and public health partners and a questionnaire that can be used to assess the utility of such frameworks in practice. An online questionnaire was developed to capture community perspectives about the utility of the RE-AIM framework. Distributed to project leads in 27 funded states in an evidence-based disease prevention initiative for older adults, 40 key stakeholders responded representing a 100% state-participation rate among the 27 funded states. Findings suggest that there is perceived utility in using the RE-AIM framework when evaluating grand-scale initiatives for older adults. The RE-AIM framework was seen as useful for planning, implementation, and evaluation with relevance for evaluators, providers, community leaders, and policy makers. Yet, the uptake was not universal, and some respondents reported difficulties in use, especially adopting the framework as a whole. This questionnaire can serve as the basis to assess ways the RE-AIM framework can be utilized by practitioners in state-wide D&I efforts. Maximal benefit can be derived from examining the assessment of RE-AIM-related knowledge and confidence as part of a continual quality assurance process. We recommend such an assessment be performed before the implementation of new funding initiatives and throughout their course to assess RE-AIM uptake and to identify areas for technical assistance.

Perceived Utility of the RE-AIM Framework for Health Promotion/Disease Prevention Initiatives for Older Adults: A Case Study from the U.S. Evidence-Based Disease Prevention Initiative

PubMed Central

Ory, Marcia G.; Altpeter, Mary; Belza, Basia; Helduser, Janet; Zhang, Chen; Smith, Matthew Lee

2015-01-01

Dissemination and implementation (D&I) frameworks are increasingly being promoted in public health research. However, less is known about their uptake in the field, especially for diverse sets of programs. Limited questionnaires exist to assess the ways that frameworks can be utilized in program planning and evaluation. We present a case study from the United States that describes the implementation of the RE-AIM framework by state aging services providers and public health partners and a questionnaire that can be used to assess the utility of such frameworks in practice. An online questionnaire was developed to capture community perspectives about the utility of the RE-AIM framework. Distributed to project leads in 27 funded states in an evidence-based disease prevention initiative for older adults, 40 key stakeholders responded representing a 100% state-participation rate among the 27 funded states. Findings suggest that there is perceived utility in using the RE-AIM framework when evaluating grand-scale initiatives for older adults. The RE-AIM framework was seen as useful for planning, implementation, and evaluation with relevance for evaluators, providers, community leaders, and policy makers. Yet, the uptake was not universal, and some respondents reported difficulties in use, especially adopting the framework as a whole. This questionnaire can serve as the basis to assess ways the RE-AIM framework can be utilized by practitioners in state-wide D&I efforts. Maximal benefit can be derived from examining the assessment of RE-AIM-related knowledge and confidence as part of a continual quality assurance process. We recommend such an assessment be performed before the implementation of new funding initiatives and throughout their course to assess RE-AIM uptake and to identify areas for technical assistance. PMID:25964897

Educational attainment and hippocampal atrophy in the Alzheimer's disease neuroimaging initiative cohort.

PubMed

Shpanskaya, Katie S; Choudhury, Kingshuk Roy; Hostage, Christopher; Murphy, Kelly R; Petrella, Jeffrey R; Doraiswamy, P Murali

2014-12-01

Subjects with higher cognitive reserve (CR) may be at a lower risk for Alzheimer's disease (AD), but the neural mechanisms underlying this are not known. Hippocampal volume loss is an early event in AD that triggers cognitive decline. Regression analyses of the effects of education on MRI-measured baseline HV in 675 subjects (201 normal, 329 with mild cognitive impairment (MCI), and 146 subjects with mild AD), adjusting for age, gender, APOE ɛ4 status and intracranial volume (ICV). Subjects were derived from the Alzheimer's Disease Neuroimaging Initiative (ADNI), a large US national biomarker study. The association between higher education and larger HV was significant in AD (P=0.014) but not in cognitively normal or MCI subjects. In AD, HV was about 8% larger in a person with 20 years of education relative to someone with 6 years of education. There was also a trend for the interaction between education and APOE ɛ4 to be significant in AD (P=0.056). A potential protective association between higher education and lower hippocampal atrophy in patients with AD appears consistent with prior epidemiologic data linking higher education levels with lower rates of incident dementia. Longitudinal studies are warranted to confirm these findings. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Disease-modifying drug initiation patterns in commercially insured multiple sclerosis patients: a retrospective cohort study

PubMed Central

2011-01-01

Background The goal of this research was to compare the demographics, clinical characteristics and treatment patterns for newly diagnosed multiple sclerosis (MS) patients in a commercial managed care population who received disease-modifying drug (DMD) therapy versus those not receiving DMD therapy. Methods A retrospective cohort study using US administrative healthcare claims identified individuals newly diagnosed with MS (no prior MS diagnosis 12 months prior using ICD-9-CM 340) and ≥ 18 years old during 2001-2007 to characterize them based on demographics, clinical characteristics, and pharmacologic therapy for one year prior to and a minimum of one year post-index. The index date was the first MS diagnosis occurring in the study period. Follow-up of subjects was done by ICD-9-CM code identification and not by actual chart review. Multivariate analyses were conducted to adjust for confounding variables. Results Patients were followed for an average of 35.7 ± 17.5 months after their index diagnosis. Forty-three percent (n = 4,462) of incident patients received treatment with at least one of the DMDs during the post-index period. Treated patients were primarily in the younger age categories of 18-44 years of age, with DMD therapy initiated an average of 5.3 ± 9.1 months after the index diagnosis. Once treatment was initiated, 27.7% discontinued DMD therapy after an average of 17.6 ± 14.6 months, and 16.5% had treatment gaps in excess of 60 days. Conclusions Nearly 60% of newly-diagnosed MS patients in this commercial managed care population remained untreated while over a quarter of treated patients stopped therapy and one-sixth experienced treatment gaps despite the risk of disease progression or a return of pre-treatment disease activity. PMID:21974973

Utility of combinations of biomarkers, cognitive markers, and risk factors to predict conversion from mild cognitive impairment to Alzheimer disease in patients in the Alzheimer's disease neuroimaging initiative.

PubMed

Gomar, Jesus J; Bobes-Bascaran, Maria T; Conejero-Goldberg, Concepcion; Davies, Peter; Goldberg, Terry E

2011-09-01

Biomarkers have become increasingly important in understanding neurodegenerative processes associated with Alzheimer disease. Markers include regional brain volumes, cerebrospinal fluid measures of pathological Aβ1-42 and total tau, cognitive measures, and individual risk factors. To determine the discriminative utility of different classes of biomarkers and cognitive markers by examining their ability to predict a change in diagnostic status from mild cognitive impairment to Alzheimer disease. Longitudinal study. We analyzed the Alzheimer's Disease Neuroimaging Initiative database to study patients with mild cognitive impairment who converted to Alzheimer disease (n = 116) and those who did not convert (n = 204) within a 2-year period. We determined the predictive utility of 25 variables from all classes of markers, biomarkers, and risk factors in a series of logistic regression models and effect size analyses. The Alzheimer's Disease Neuroimaging Initiative public database. Primary outcome measures were odds ratios, pseudo- R(2)s, and effect sizes. In comprehensive stepwise logistic regression models that thus included variables from all classes of markers, the following baseline variables predicted conversion within a 2-year period: 2 measures of delayed verbal memory and middle temporal lobe cortical thickness. In an effect size analysis that examined rates of decline, change scores for biomarkers were modest for 2 years, but a change in an everyday functional activities measure (Functional Assessment Questionnaire) was considerably larger. Decline in scores on the Functional Assessment Questionnaire and Trail Making Test, part B, accounted for approximately 50% of the predictive variance in conversion from mild cognitive impairment to Alzheimer disease. Cognitive markers at baseline were more robust predictors of conversion than most biomarkers. Longitudinal analyses suggested that conversion appeared to be driven less by changes in the neurobiologic

Cognitive function in chronic obstructive pulmonary disease: relationship to global initiative for chronic obstructive lung disease 2011 categories.

PubMed

Tulek, Baykal; Atalay, Nart Bedin; Yildirim, Gulfem; Kanat, Fikret; Süerdem, Mecit

2014-08-01

Recently, comorbidities such as impaired cognitive function have been attracting more focus when considering the management of chronic obstructive pulmonary disease (COPD). Here we investigated the relationship between cognitive function and the categories given in the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines in 2011. Specifically, after controlling for non-COPD covariates, we assessed the clinical features that may be predictive of cognitive impairment in patients with COPD. We recruited 119 stable patients with mild to very severe COPD. We administered a broad array of standardized neuropsychological tests that assessed cognitive functions in the domains of attention, memory, psychomotor coordination and language. Cognitive scores were significantly different between patients falling within GOLD 2011 categories. Scores were lower in patients with high future risk compared with low future risk. In parallel, there were significant differences in cognitive function between COPD patient subgroups when patients were grouped according to the forced expiratory volume in 1 s, exacerbation history and C-reactive protein levels. After controlling for non-COPD predictors, only exacerbation history remained a significant predictor of cognitive scores. The number of exacerbation events in a year may be used as a predictor of cognitive impairment in patients with COPD. © 2014 Asian Pacific Society of Respirology.

Influence of socioeconomic and demographic status on spirometry testing in patients initiating medication targeting obstructive lung disease: a population-based cohort study.

PubMed

Koefoed, Mette M; Søndergaard, Jens; Christensen, René dePont; Jarbøl, Dorte E

2013-06-14

Socioeconomic status is known to influence the prevalence, severity and mortality of obstructive lung diseases, but it is uncertain whether it affects the use of diagnostic spirometry in patients initiating treatment for these conditions. The objective of this paper was to examine a possible association between education, income, labour market affiliation, cohabitation status and having spirometry performed when initiating medication targeting obstructive pulmonary disease. We conducted a population-based cohort study. Danish national registers were linked, retrieving data on prescriptions, spirometry testing, socioeconomic and demographic variables in all first time users of medication targeting obstructive lung disease in 2008. A total of 37,734 persons were included and approximately half of the cohort had spirometry performed. Among medication users under 65 years of age, being unemployed was significantly associated with reduced odds of having spirometry performed, the strongest association was seen in men (OR = 0.82, CI = 0.73-0.91). Medium income was associated with increased odds of having spirometry performed in men (OR =1.18, CI = 1.06-1.30) and high educational level (>12 years) was associated with reduced odds of having spirometry performed in women (OR = 0.86, CI = 0.78-0.94). Cohabitation status was not associated with having spirometry performed. Among medication users over 65 years of age, living alone was associated with reduced odds of having spirometry performed among men (OR = 0.78, CI = 0.69-0.88). Social inequity in spirometry testing among patients initiating medication targeting obstructive lung disease was confirmed in this study. Increased focus on spirometry testing among elderly men living alone, among the unemployed and among women with higher education is required when initiating medication.

Chronic inflammatory demyelinating polyneuropathy-like neuropathy as an initial presentation of Crohn's disease.

PubMed

Kim, Suji; Kang, Seok-Jae; Oh, Ki-Wook; Ahn, Byung Kyu; Lee, Hang Lak; Han, Dong Soo; Jang, Kiseok; Kim, Young Seo

2015-03-28

Chronic inflammatory demyelinating polyneuropathy (CIDP) is a rare complication of Crohn's disease (CD), and it is uncertain whether it is associated with CD itself or with its treatment. We describe a case of CIDP-like neuropathy as an initial symptom of CD. The neurologic symptoms of the patient which responded partially to intravenous immunoglobulin (IVIG) recovered after resection of the appendiceal CD. A 17-year-old male had experienced three separate attacks of motor weakness and paresthesia of all four extremities over a period of 7 months. The electrophysiologic findings revealed a demyelinating sensory-motor polyneuropathy which was compatible with CIDP. However, repeated intravenous IVIG (2 g/kg) treatment gave only a partial response. Four days after the last discharge, he was diagnosed as appendiceal CD after surgical resection of a periappendiceal abscess. His neurologic symptoms and electrophysiologic findings recovered without any maintenance therapy. CIDP-like neuropathy can be an initial presentation of CD, and recovery of the CIDP symptoms may result from resection of the CD. Clinicians should be aware of the possibility of CD in patients with intractable CIDP symptoms.

Preventing cardiac diseases in childhood.

PubMed

Petropoulos, Andreas; Ehringer-Schetitska, Doris; Fritsch, Peter; Jokinen, Eero; Dalla Pozza, Robert; Oberhoffer, Renate

2015-01-01

activities. Screening to early detect and treating existent risk factors (RF) for CVD as well as preventing obesity and hypertension, contributes in lowering the burden of CVD. Specific screening tests as laboratory measurements of lipids, fasting glucose or regular measurements of Blood Pressure and waist to hip ratio in children with a family history of CVD or other co-morbidity that provokes accelerating atherosclerosis must be done on a regular basis. Since 2010, four European studies reporting the test accuracy of routine pulse oximetry screening, in over 150.000 babies, have delivered new data. A systematic review and meta-analysis of 230.000 screened babies, reported high specificity, moderate sensitivity and a low false-positive rate. Routine screening for critical CHD using pulse oximetry is being increasingly supported and was added to the recommended uniform screening panel in the USA in 2011. Evaluating children with CHD before their involvement in sport activities, so a clear view in what they can and what they can't to is vital for their safety. For children involved in competitive or leisure sport activities, an initial evaluation and a yearly F/U is vital. In cases of near SCD events an additional thorough investigation and appropriate management is required. Investigating the severity of the existing RF and cooperating with Pediatricians in their treatment (e.g. heredity forms of hyperlipidemias, existing hypertension) of them is essential. Furthermore preventing acceleration of atherosclerosis in patients with: Diabetes Mellitus I, II, chronic renal disease, post Kawasaki disease, post heart transplantation patients, Cardio-Metabolic Syndrome patients, by eradicating RF primordially or by alternating them by opposing a healthy life style or by medicine treatment, has sown in many studies to post pone clinical events in adulthood. As many studies have proved the role of preventive measures that can alternate the outcome of cardiac diseases in childhood. AEPC

Dracunculiasis (Guinea Worm Disease) and the Eradication Initiative

PubMed Central

Cairncross, Sandy; Muller, Ralph; Zagaria, Nevio

2002-01-01

Dracunculiasis, also known as guinea worm disease, is caused by the large female of the nematode Dracunculus medinensis, which emerges painfully and slowly from the skin, usually on the lower limbs. The disease can infect animals, and sustainable animal cycles occur in North America and Central Asia but do not act as reservoirs of human infection. The disease is endemic across the Sahel belt of Africa from Mauritania to Ethiopia, having been eliminated from Asia and some African countries. It has a significant socioeconomic impact because of the temporary disability that it causes. Dracunculiasis is exclusively caught from drinking water, usually from ponds. A campaign to eradicate the disease was launched in the 1980s and has made significant progress. The strategy of the campaign is discussed, including water supply, health education, case management, and vector control. Current issues including the integration of the campaign into primary health care and the mapping of cases by using geographic information systems are also considered. Finally, some lessons for other disease control and eradication programs are outlined. PMID:11932231

Newly Diagnosed Meniere's Disease: Clinical Course With Initiation of Noninvasive Treatment Including an Accounting of Vestibular Migraine.

PubMed

Sbeih, Firas; Christov, Florian; Gluth, Michael B

2018-05-01

To describe the course of Meniere's disease with noninvasive treatment during the first few years after initial diagnosis. A retrospective review of consecutive patients with newly diagnosed definite Meniere's disease between 2013 and 2016 and a minimum follow-up of 1 year. Patients received a written plan for low sodium, water therapy, and treatment with a diuretic and/or betahistine. Subjects were screened and treated for vestibular migraine as needed. Vertigo control and hearing status at most recent follow-up were assessed. Forty-four subjects had an average follow up of 24.3 months. Thirty-four percent had Meniere's disease and vestibular migraine, and 84% had unilateral Meniere's disease. Seventy-five percent had vertigo well controlled at most recent follow-up, with only noninvasive treatments. Age, gender, body mass index, presence of vestibular migraine, bilateral disease, and duration of follow-up did not predict noninvasive treatment failure. Worse hearing threshold at 250 Hz and lower pure tone average (PTA) at the time of diagnosis did predict failure. Fifty-two percent of ears had improved PTA at most recent visit, 20% had no change, and 28% were worse Conclusions: Encountering excellent vertigo control and stable hearing after a new diagnosis of Meniere's disease is possible with noninvasive treatments. Worse hearing status at diagnosis predicted treatment failure.

Disease progression model for Clinical Dementia Rating–Sum of Boxes in mild cognitive impairment and Alzheimer’s subjects from the Alzheimer’s Disease Neuroimaging Initiative

PubMed Central

Samtani, Mahesh N; Raghavan, Nandini; Novak, Gerald; Nandy, Partha; Narayan, Vaibhav A

2014-01-01

Background The objective of this analysis was to develop a nonlinear disease progression model, using an expanded set of covariates that captures the longitudinal Clinical Dementia Rating Scale–Sum of Boxes (CDR–SB) scores. These were derived from the Alzheimer’s Disease Neuroimaging Initiative ADNI-1 study, of 301 Alzheimer’s disease and mild cognitive impairment patients who were followed for 2–3 years. Methods The model describes progression rate and baseline disease score as a function of covariates. The covariates that were tested fell into five groups: a) hippocampal volume; b) serum and cerebrospinal fluid (CSF) biomarkers; c) demographics and apolipoprotein Epsilon 4 (ApoE4) allele status; d) baseline cognitive tests; and e) disease state and comedications. Results Covariates associated with baseline disease severity were disease state, hippocampal volume, and comedication use. Disease progression rate was influenced by baseline CSF biomarkers, Trail-Making Test part A score, delayed logical memory test score, and current level of impairment as measured by CDR–SB. The rate of disease progression was dependent on disease severity, with intermediate scores around the inflection point score of 10 exhibiting high disease progression rate. The CDR–SB disease progression rate in a typical patient, with late mild cognitive impairment and mild Alzheimer’s disease, was estimated to be approximately 0.5 and 1.4 points/year, respectively. Conclusions In conclusion, this model describes disease progression in terms of CDR–SB changes in patients and its dependency on novel covariates. The CSF biomarkers included in the model discriminate mild cognitive impairment subjects as progressors and nonprogressors. Therefore, the model may be utilized for optimizing study designs, through patient population enrichment and clinical trial simulations. PMID:24926196

Polio Eradication Initiative contribution in strengthening immunization and integrated disease surveillance data management in WHO African region, 2014.

PubMed

Poy, Alain; Minkoulou, Etienne; Shaba, Keith; Yahaya, Ali; Gaturuku, Peter; Dadja, Landoh; Okeibunor, Joseph; Mihigo, Richard; Mkanda, Pascal

2016-10-10

The PEI Programme in the WHO African region invested in recruitment of qualified staff in data management, developing data management system and standards operating systems since the revamp of the Polio Eradication Initiative in 1997 to cater for data management support needs in the Region. This support went beyond polio and was expanded to routine immunization and integrated surveillance of priority diseases. But the impact of the polio data management support to other programmes such as routine immunization and disease surveillance has not yet been fully documented. This is what this article seeks to demonstrate. We reviewed how Polio data management area of work evolved progressively along with the expansion of the data management team capacity and the evolution of the data management systems from initiation of the AFP case-based to routine immunization, other case based disease surveillance and Supplementary immunization activities. IDSR has improved the data availability with support from IST Polio funded data managers who were collecting them from countries. The data management system developed by the polio team was used by countries to record information related to not only polio SIAs but also for other interventions. From the time when routine immunization data started to be part of polio data management team responsibility, the number of reports received went from around 4000 the first year (2005) to >30,000 the second year and to >47,000 in 2014. Polio data management has helped to improve the overall VPD, IDSR and routine data management as well as emergency response in the Region. As we approach the polio end game, the African Region would benefit in using the already set infrastructure for other public health initiative in the Region. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Japanese and North American Alzheimer's Disease Neuroimaging Initiative studies: Harmonization for international trials.

PubMed

Iwatsubo, Takeshi; Iwata, Atsushi; Suzuki, Kazushi; Ihara, Ryoko; Arai, Hiroyuki; Ishii, Kenji; Senda, Michio; Ito, Kengo; Ikeuchi, Takeshi; Kuwano, Ryozo; Matsuda, Hiroshi; Sun, Chung-Kai; Beckett, Laurel A; Petersen, Ronald C; Weiner, Michael W; Aisen, Paul S; Donohue, Michael C

2018-05-08

We conducted Japanese Alzheimer's Disease Neuroimaging Initiative (J-ADNI) and compared the basic characteristics and progression profiles with those of ADNI in North America. A total of 537 Japanese subjects with normal cognition, late amnestic mild cognitive impairment (LMCI), or mild Alzheimer's disease (AD) were enrolled using the same criteria as ADNI. Rates of changes in representative cognitive or functional measures were compared for amyloid positron emission tomography- or cerebrospinal fluid amyloid β(1-42)-positive LMCI and mild AD between J-ADNI and ADNI. Amyloid positivity rates were significantly higher in normal cognition of ADNI but at similar levels in LMCI and mild AD between J-ADNI and ADNI. Profiles of decline in cognitive or functional measures in amyloid-positive LMCI in J-ADNI (n = 75) and ADNI (n = 269) were remarkably similar, whereas those in mild AD were milder in J-ADNI (n = 73) compared with ADNI (n = 230). These results support the feasibility of bridging of clinical trials in the prodromal stage of AD between Asia and western countries. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Enhancing patient engagement in chronic disease self-management support initiatives in Australia: the need for an integrated approach.

PubMed

Jordan, Joanne E; Briggs, Andrew M; Brand, Caroline A; Osborne, Richard H

2008-11-17

Although emphasis on the prevention of chronic disease is important, governments in Australia need to balance this with continued assistance to the 77% of Australians reported to have at least one long-term medical condition. Self-management support is provided by health care and community services to enhance patients' ability to care for their chronic conditions in a cooperative framework. In Australia, there is a range of self-management support initiatives that have targeted patients (most notably, chronic disease self-management education programs) and health professionals (financial incentives, education and training). To date, there has been little coordination or integration of these self-management initiatives to enhance the patient-health professional clinical encounter. If self-management support is to work, there is a need to better understand the infrastructure, systems and training that are required to engage the key stakeholders - patients, carers, health professionals, and health care organisations. A coordinated approach is required in implementing these elements within existing and new health service models to enhance uptake and sustainability.

Models of Disease Vector Control: When Can Aggressive Initial Intervention Lower Long-Term Cost?

PubMed

Oduro, Bismark; Grijalva, Mario J; Just, Winfried

2018-04-01

Insecticide spraying of housing units is an important control measure for vector-borne infections such as Chagas disease. As vectors may invade both from other infested houses and sylvatic areas and as the effectiveness of insecticide wears off over time, the dynamics of (re)infestations can be approximated by [Formula: see text]-type models with a reservoir, where housing units are treated as hosts, and insecticide spraying corresponds to removal of hosts. Here, we investigate three ODE-based models of this type. We describe a dual-rate effect where an initially very high spraying rate can push the system into a region of the state space with low endemic levels of infestation that can be maintained in the long run at relatively moderate cost, while in the absence of an aggressive initial intervention the same average cost would only allow a much less significant reduction in long-term infestation levels. We determine some sufficient and some necessary conditions under which this effect occurs and show that it is robust in models that incorporate some heterogeneity in the relevant properties of housing units.

Absence of αvβ6 Integrin Is Linked to Initiation and Progression of Periodontal Disease

PubMed Central

Ghannad, Farzin; Nica, Daniela; Garcia Fulle, Maria I.; Grenier, Daniel; Putnins, Edward E.; Johnston, Sarah; Eslami, Ameneh; Koivisto, Leeni; Jiang, Guoqiao; McKee, Marc D.; Häkkinen, Lari; Larjava, Hannu

2008-01-01

Integrin αvβ6 is generally not expressed in adult epithelia but is induced in wound healing, cancer, and certain fibrotic disorders. Despite this generalized absence, we observed that αvβ6 integrin is constitutively expressed in the healthy junctional epithelium linking the gingiva to tooth enamel. Moreover, expression of αvβ6 integrin was down-regulated in human periodontal disease, a common medical condition causing tooth loss and also contributing to the development of cardiovascular diseases by increasing the total systemic inflammatory burden. Remarkably, integrin β6 knockout mice developed classic signs of spontaneous, chronic periodontal disease with characteristic inflammation, epithelial down-growth, pocket formation, and bone loss around the teeth. Integrin αvβ6 acts as a major activator of transforming growth factor-β1 (TGF-β1), a key anti-inflammatory regulator in the immune system. Co-expression of TGF-β1 and αvβ6 integrin was observed in the healthy junctional epithelium. Moreover, an antibody that blocks αvβ6 integrin-mediated activation of TGF-β1 initiated inflammatory periodontal disease in a rat model of gingival inflammation. Thus, αvβ6 integrin is constitutively expressed in the epithelium sealing the gingiva to the tooth and plays a central role in protection against inflammatory periodontal disease through activation of TGF-β1. PMID:18385522

Longitudinal changes in white matter disease and cognition in the first year of the Alzheimer disease neuroimaging initiative.

PubMed

Carmichael, Owen; Schwarz, Christopher; Drucker, David; Fletcher, Evan; Harvey, Danielle; Beckett, Laurel; Jack, Clifford R; Weiner, Michael; DeCarli, Charles

2010-11-01

To evaluate relationships between magnetic resonance imaging (MRI)-based measures of white matter hyperintensities (WMHs), measured at baseline and longitudinally, and 1-year cognitive decline using a large convenience sample in a clinical trial design with a relatively mild profile of cardiovascular risk factors. Convenience sample in a clinical trial design. A total of 804 participants in the Alzheimer Disease Neuroimaging Initiative who received MRI scans, cognitive testing, and clinical evaluations at baseline, 6-month follow-up, and 12-month follow-up visits. For each scan, WMHs were detected automatically on coregistered sets of T1, proton density, and T2 MRI images using a validated method. Mixed-effects regression models evaluated relationships between risk factors for WMHs, WMH volume, and change in outcome measures including Mini-Mental State Examination (MMSE), Alzheimer Disease Assessment Scale-Cognitive Subscale (ADAS-Cog), and Clinical Dementia Rating Scale sum of boxes scores. Covariates in these models included race, sex, years of education, age, apolipoprotein E genotype, baseline clinical diagnosis (cognitively normal, mild cognitive impairment, or Alzheimer disease), cardiovascular risk score, and MRI-based hippocampal and brain volumes. Higher baseline WMH volume was associated with greater subsequent 1-year increase in ADAS-Cog and decrease in MMSE scores. Greater WMH volume at follow-up was associated with greater ADAS-Cog and lower MMSE scores at follow-up. Higher baseline age and cardiovascular risk score and more impaired baseline clinical diagnosis were associated with higher baseline WMH volume. White matter hyperintensity volume predicts 1-year cognitive decline in a relatively healthy convenience sample that was similar to clinical trial samples, and therefore should be considered as a covariate of interest at baseline and longitudinally in future AD treatment trials.

The Alzheimer's Disease Neuroimaging Initiative: A review of papers published since its inception

PubMed Central

Weiner, Michael W.; Veitch, Dallas P.; Aisen, Paul S.; Beckett, Laurel A.; Cairns, Nigel J.; Green, Robert C.; Harvey, Danielle; Jack, Clifford R.; Jagust, William; Liu, Enchi; Morris, John C.; Petersen, Ronald C.; Saykin, Andrew J.; Schmidt, Mark E.; Shaw, Leslie; Shen, Li; Siuciak, Judith A.; Soares, Holly; Toga, Arthur W.; Trojanowski, John Q.

2014-01-01

The Alzheimer's Disease Neuroimaging Initiative (ADNI) is an ongoing, longitudinal, multicenter study designed to develop clinical, imaging, genetic, and biochemical biomarkers for the early detection and tracking of Alzheimer's disease (AD). The study aimed to enroll 400 subjects with early mild cognitive impairment (MCI), 200 subjects with early AD, and 200 normal control subjects; $67 million funding was provided by both the public and private sectors, including the National Institute on Aging, 13 pharmaceutical companies, and 2 foundations that provided support through the Foundation for the National Institutes of Health. This article reviews all papers published since the inception of the initiative and summarizes the results as of February 2011. The major accomplishments of ADNI have been as follows: (1) the development of standardized methods for clinical tests, magnetic resonance imaging (MRI), positron emission tomography (PET), and cerebrospinal fluid (CSF) biomarkers in a multicenter setting; (2) elucidation of the patterns and rates of change of imaging and CSF biomarker measurements in control subjects, MCI patients, and AD patients. CSF biomarkers are consistent with disease trajectories predicted by β-amyloid cascade (Hardy, J Alzheimers Dis 2006;9(Suppl 3):151–3) and tau-mediated neurodegeneration hypotheses for AD, whereas brain atrophy and hypometabolism levels show predicted patterns but exhibit differing rates of change depending on region and disease severity; (3) the assessment of alternative methods of diagnostic categorization. Currently, the best classifiers combine optimum features from multiple modalities, including MRI, [18F]-fluorodeoxyglucose-PET, CSF biomarkers, and clinical tests; (4) the development of methods for the early detection of AD. CSF biomarkers, β-amyloid 42 and tau, as well as amyloid PET may reflect the earliest steps in AD pathology in mildly symptomatic or even nonsymptomatic subjects, and are leading candidates

Intrinsic functional component analysis via sparse representation on Alzheimer's disease neuroimaging initiative database.

PubMed

Jiang, Xi; Zhang, Xin; Zhu, Dajiang

2014-10-01

Alzheimer's disease (AD) is the most common type of dementia (accounting for 60% to 80%) and is the fifth leading cause of death for those people who are 65 or older. By 2050, one new case of AD in United States is expected to develop every 33 sec. Unfortunately, there is no available effective treatment that can stop or slow the death of neurons that causes AD symptoms. On the other hand, it is widely believed that AD starts before development of the associated symptoms, so its prestages, including mild cognitive impairment (MCI) or even significant memory concern (SMC), have received increasing attention, not only because of their potential as a precursor of AD, but also as a possible predictor of conversion to other neurodegenerative diseases. Although these prestages have been defined clinically, accurate/efficient diagnosis is still challenging. Moreover, brain functional abnormalities behind those alterations and conversions are still unclear. In this article, by developing novel sparse representations of whole-brain resting-state functional magnetic resonance imaging signals and by using the most updated Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset, we successfully identified multiple functional components simultaneously, and which potentially represent those intrinsic functional networks involved in the resting-state activities. Interestingly, these identified functional components contain all the resting-state networks obtained from traditional independent-component analysis. Moreover, by using the features derived from those functional components, it yields high classification accuracy for both AD (94%) and MCI (92%) versus normal controls. Even for SMC we can still have 92% accuracy.

A US database study characterizing patients initiating a budesonide-formoterol combination versus tiotropium bromide as initial maintenance therapy for chronic obstructive pulmonary disease.

PubMed

Kern, David M; Williams, Setareh A; Tunceli, Ozgur; Wessman, Catrin; Zhou, Siting; Pethick, Ned; Elhefni, Hanaa; Trudo, Frank

2014-01-01

To compare clinical and demographic characteristics, resource utilization and costs of chronic obstructive pulmonary disease (COPD) patients prior to initiating budesonide-formoterol combination (BFC) or tiotropium-maintenance therapy. This cross-sectional study used claims-based diagnosis to identify COPD patients in the HealthCore Integrated Research Database who initiated BFC or tiotropium therapy between March 1, 2009 and January 31, 2012 (intake period); the index date was defined as the initial prescription fill for either agent. Patients diagnosed with respiratory tract cancer or receiving inhaled corticosteroids/long-acting β2-adrenergic agonists or tiotropium in 12 months prior to index date were excluded. Categorical variables were evaluated with χ(2) tests; mean cost differences were evaluated using γ-regression. Overall, 6,940 BFC and 10,831 tiotropium patients were identified. The BFC group was younger (mean age 64 versus 67 years), with a greater proportion of females (54% versus 51%). BFC-treated patients had more comorbid respiratory conditions, including asthma (25% versus 13%), but fewer comorbid cardiovascular conditions, including atherosclerosis (7% versus 10%) and myocardial infarction (4% versus 6%). A greater proportion of BFC patients received prior respiratory medication, including oral corticosteroids (46% versus 35%) and short-acting β2-agonists (44% versus 35%). Tiotropium-treated patients had a greater mean number of COPD-related outpatient visits (4.6 versus 4.1). BFC-treated patients had lower total all-cause ($17,259 versus $17,926) and COPD-related ($1,718 versus $1,930) health care costs, driven by lower all-cause and COPD-related inpatient expenditures. Initiators of BFC or tiotropium showed differences in clinical and demographic characteristics and health care utilization and costs prior to starting COPD maintenance therapy.

Initial cognitive decline is associated with cortical thinning in early Parkinson disease

PubMed Central

Svenningsson, Per; Weintraub, Daniel; Brønnick, Kolbjørn; Lebedev, Alexander; Westman, Eric; Aarsland, Dag

2014-01-01

Objectives: Our aim was to assess cortical thickness in a large multicenter cohort of drug-naive patients with early Parkinson disease (PD), with and without mild cognitive impairment (MCI), and explore the cognitive correlates of regional cortical thinning. Methods: One hundred twenty-three newly diagnosed patients with PD and 56 healthy controls with 3-tesla structural MRI scans and complete neuropsychological assessment from the Parkinson's Progression Markers Initiative were included. Modified Movement Disorders Society Task Force level II criteria were applied to diagnose MCI in PD. FreeSurfer image processing and analysis software was used to measure cortical thickness across groups and the association with cognitive domains and tests. Results: In patients with MCI, atrophy was found in temporal, parietal, frontal, and occipital areas compared with controls. Specific regional thinning in the right inferior temporal cortex was also found in cognitively normal patients. Memory, executive, and visuospatial performance was associated with temporoparietal and superior frontal thinning, suggesting a relationship between cognitive impairment and both anterior and posterior cortical atrophy in the whole patient sample. Conclusions: These findings confirm that MCI is associated with widespread cortical atrophy. In addition, they suggest that regional cortical thinning is already present at the time of diagnosis in patients with early, untreated PD who do not meet the criteria for MCI. Together, the results indicate that cortical thinning can serve as a marker for initial cognitive decline in early PD. PMID:24808018

Prayer and the Registered Nurse (PRN): nurses' reports of ease and dis-ease with patient-initiated prayer request.

PubMed

Minton, Mary E; Isaacson, Mary; Banik, Deborah

2016-09-01

To explore nurse comfort with patient-initiated prayer request scenarios. Spiritual care is fundamental to patient care evidenced by Joint Commission requirement of a spiritual assessment on a patient's hospital admission. Prayer is an assessment component. Patients may seek solace and support by requesting prayer from the bedside nurse, the nurse may lack confidence in responding. Absent in the literature are reports specific to nurses' comfort when patients initiate prayer requests. Cross-sectional mixed methods study. Data were collected in early 2014 from 134 nurses in the USA via an online survey using QuestionPro. The qualitative results reported here were collated by scenario and analysed using thematic analysis. The scenario responses revealed patterns of ease and dis-ease in response to patient requests for prayer. The pattern of ease of prayer with patients revealed three themes: open to voice of calm or silence; physical or spiritual; can I call the chaplain. For these nurses, prayer is a natural component of nursing care, as the majority of responses to all scenarios demonstrated an overwhelming ease in response and capacity to pray with patients on request. The pattern of dis-ease of prayer with patients distinguished two themes: cautious hesitancy and whose God. These nurses experienced dis-ease with the patient's request no matter the situation. Educators and administrators must nurture opportunities for students and nurses to learn about and engage in the reflective preparation needed to respond to patient prayer requests. © 2016 John Wiley & Sons Ltd.

Self-triggered assistive stimulus training improves step initiation in persons with Parkinson’s disease

PubMed Central

2013-01-01

Background Prior studies demonstrated that hesitation-prone persons with Parkinson’s disease (PDs) acutely improve step initiation using a novel self-triggered stimulus that enhances lateral weight shift prior to step onset. PDs showed reduced anticipatory postural adjustment (APA) durations, earlier step onsets, and faster 1st step speed immediately following stimulus exposure. Objective This study investigated the effects of long-term stimulus exposure. Methods Two groups of hesitation-prone subjects with Parkinson’s disease (PD) participated in a 6-week step-initiation training program involving one of two stimulus conditions: 1) Drop. The stance-side support surface was lowered quickly (1.5 cm); 2) Vibration. A short vibration (100 ms) was applied beneath the stance-side support surface. Stimuli were self-triggered by a 5% reduction in vertical force under the stance foot during the APA. Testing was at baseline, immediately post-training, and 6 weeks post-training. Measurements included timing and magnitude of ground reaction forces, and step speed and length. Results Both groups improved their APA force modulation after training. Contrary to previous results, neither group showed reduced APA durations or earlier step onset times. The vibration group showed 55% increase in step speed and a 39% increase in step length which were retained 6 weeks post-training. The drop group showed no stepping-performance improvements. Conclusions The acute sensitivity to the quickness-enhancing effects of stimulus exposure demonstrated in previous studies was supplanted by improved force modulation following prolonged stimulus exposure. The results suggest a potential approach to reduce the severity of start hesitation in PDs, but further study is needed to understand the relationship between short- and long-term effects of stimulus exposure. PMID:23363975

Ventricular enlargement as a possible measure of Alzheimer's disease progression validated using the Alzheimer's disease neuroimaging initiative database

PubMed Central

Nestor, Sean M.; Rupsingh, Raul; Borrie, Michael; Smith, Matthew; Accomazzi, Vittorio; Wells, Jennie L.; Fogarty, Jennifer

2008-01-01

Ventricular enlargement may be an objective and sensitive measure of neuropathological change associated with mild cognitive impairment (MCI) and Alzheimer's disease (AD), suitable to assess disease progression for multi-centre studies. This study compared (i) ventricular enlargement after six months in subjects with MCI, AD and normal elderly controls (NEC) in a multi-centre study, (ii) volumetric and cognitive changes between Apolipoprotein E genotypes, (iii) ventricular enlargement in subjects who progressed from MCI to AD, and (iv) sample sizes for multi-centre MCI and AD studies based on measures of ventricular enlargement. Three dimensional T1-weighted MRI and cognitive measures were acquired from 504 subjects (NEC n = 152, MCI n = 247 and AD n = 105) participating in the multi-centre Alzheimer's Disease Neuroimaging Initiative. Cerebral ventricular volume was quantified at baseline and after six months using semi-automated software. For the primary analysis of ventricle and neurocognitive measures, between group differences were evaluated using an analysis of covariance, and repeated measures t-tests were used for within group comparisons. For secondary analyses, all groups were dichotomized for Apolipoprotein E genotype based on the presence of an ε4 polymorphism. In addition, the MCI group was dichotomized into those individuals who progressed to a clinical diagnosis of AD, and those subjects that remained stable with MCI after six months. Group differences on neurocognitive and ventricle measures were evaluated by independent t-tests. General sample size calculations were computed for all groups derived from ventricle measurements and neurocognitive scores. The AD group had greater ventricular enlargement compared to both subjects with MCI (P = 0.0004) and NEC (P < 0.0001), and subjects with MCI had a greater rate of ventricular enlargement compared to NEC (P = 0.0001). MCI subjects that progressed to clinical AD after six months had greater ventricular

Adult bacterial meningitis-a quality registry study: earlier treatment and favourable outcome if initial management by infectious diseases physicians.

PubMed

Grindborg, Ö; Naucler, P; Sjölin, J; Glimåker, M

2015-06-01

Acute bacterial meningitis (ABM) is challenging for the admitting physician because it is a rare but fulminant disease, usually presenting without typical symptoms, and rapid treatment is pivotal. The purpose of this study was to evaluate the effect of initial management by infectious diseases (ID) physicians vs. non-ID physicians. A total of 520 consecutive adults (>17 years old), 110 with initial ID management and 410 with non-ID management, registered in the Swedish quality registry for community-acquired ABM January 2008 to December 2013, were analysed retrospectively. Primary outcome was appropriate treatment with antibiotics and corticosteroids <1 hour from admission. Secondary analyses were mortality during hospital stay and persisting neurological and hearing deficits at follow-up after 2 to 6 months. Differences in diagnostic treatment sequences also were analysed. Appropriate treatment <1 hour from admission was achieved significantly more often (41%) by ID physicians vs. non-ID physicians (24%) with an odds ratio (OR) of 2.4 (95% confidence interval [CI]: 1.40 to 4.14; p < 0.01) adjusted for confounders. The door-to-antibiotic time was significantly shorter, and significantly more patients were administered corticosteroids together with the first doses of antibiotics in the ID group. A trend of decreased mortality (4.5% vs. 8.0%) and sequelae at follow-up (24% vs. 44%; adjusted OR 0.55: 95% CI 0.31 to 1.00; p 0.05) were observed in the ID group vs. the non-ID group. Antibiotics were started without prior neuroimaging more often in the ID group (86% vs. 57%; p < 0.001). Initial management at the emergency department by ID physicians is associated with earlier appropriate treatment, more appropriate diagnostic treatment sequences and favourable outcome. Copyright © 2015 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Risk factors for late-stage HIV disease presentation at initial HIV diagnosis in Durban, South Africa.

PubMed

Drain, Paul K; Losina, Elena; Parker, Gary; Giddy, Janet; Ross, Douglas; Katz, Jeffrey N; Coleman, Sharon M; Bogart, Laura M; Freedberg, Kenneth A; Walensky, Rochelle P; Bassett, Ingrid V

2013-01-01

After observing persistently low CD4 counts at initial HIV diagnosis in South Africa, we sought to determine risk factors for late-stage HIV disease presentation among adults. We surveyed adults prior to HIV testing at four outpatient clinics in Durban from August 2010 to November 2011. All HIV-infected adults were offered CD4 testing, and late-stage HIV disease was defined as a CD4 count <100 cells/mm(3). We used multivariate regression models to determine the effects of sex, emotional health, social support, distance from clinic, employment, perceived barriers to receiving healthcare, and foregoing healthcare to use money for food, clothing, or housing ("competing needs to healthcare") on presentation with late-stage HIV disease. Among 3,669 adults screened, 830 were enrolled, newly-diagnosed with HIV and obtained a CD4 result. Among those, 279 (33.6%) presented with late-stage HIV disease. In multivariate analyses, participants who lived ≥5 kilometers from the test site [adjusted odds ratio (AOR) 2.8, 95% CI 1.7-4.7], reported competing needs to healthcare (AOR 1.7, 95% CI 1.2-2.4), were male (AOR 1.7, 95% CI 1.2-2.3), worked outside the home (AOR 1.5, 95% CI 1.1-2.1), perceived health service delivery barriers (AOR 1.5, 95% CI 1.1-2.1), and/or had poor emotional health (AOR 1.4, 95% CI 1.0-1.9) had higher odds of late-stage HIV disease presentation. Independent risk factors for late-stage HIV disease presentation were from diverse domains, including geographic, economic, demographic, social, and psychosocial. These findings can inform various interventions, such as mobile testing or financial assistance, to reduce the risk of presentation with late-stage HIV disease.

The Alzheimer’s Disease Neuroimaging Initiative: A review of papers published since its inception

PubMed Central

Weiner, Michael W.; Veitch, Dallas P.; Aisen, Paul S.; Beckett, Laurel A.; Cairns, Nigel J.; Green, Robert C.; Harvey, Danielle; Jack, Clifford R.; Jagust, William; Liu, Enchi; Morris, John C.; Petersen, Ronald C.; Saykin, Andrew J.; Schmidt, Mark E.; Shaw, Leslie; Siuciak, Judith A.; Soares, Holly; Toga, Arthur W.; Trojanowski, John Q.

2012-01-01

The Alzheimer’s Disease Neuroimaging Initiative (ADNI) is an ongoing, longitudinal, multicenter study designed to develop clinical, imaging, genetic and biochemical biomarkers for the early detection and tracking of Alzheimer’s disease (AD). The study aimed to enroll 400 subjects with early mild cognitive impairment (MCI), 200 subjects with early AD and 200 normal controls and $67 million funding was provided by both the public and private sectors including the National Institutes on Aging, thirteen pharmaceutical companies and two Foundations that provided support through the Foundation for NIH (FNIH). This article reviews all papers published since the inception of the initiative and summarizes the results as of February, 2011. The major accomplishments of ADNI have been 1) the development of standardized methods for clinical, magnetic resonance imaging (MRI) and positron emission tomography (PET) and cerebrospinal fluid (CSF) biomarkers in a multi-center setting; 2) elucidation of the patterns and rates of change of imaging and CSF biomarker measurements in control, MCI and AD patients. CSF biomarkers are consistent with disease trajectories predicted by β amyloid (Aβ) cascade [1] and tau mediated neurodegeneration hypotheses for AD while brain atrophy and hypometabolism levels show predicted patterns but exhibit differing rates of change depending on region and disease severity; 3) the assessment of alternative methods of diagnostic categorization. Currently, the best classifiers combine optimum features from multiple modalities including MRI, FDG-PET, CSF biomarkers and clinical tests; 4) the development of methods for the early detection of AD. CSF biomarkers, Aβ42 and tau as well as amyloid PET may reflect the earliest steps in AD pathology in mildly or even non-symptomatic subjects and are leading candidates for the detection of AD in its preclinical stages; 5) the improvement of clinical trial efficiency through the identification of subjects most

Community Movement in Applying Mosquito Net on House Ventilations: An Initial Support for Green Architecture to Decrease Dengue Disease in Bandung Indonesia

NASA Astrophysics Data System (ADS)

Rinawan, F. R.; Dewi, I. P. P.; Haifa, G. Z.; Suharno, K. D.; Oktavinus, K.; Lyn, P. S.

2017-10-01

Green architecture still has risk to dengue disease when trees cover house roofs’ gutter. This study was aimed to continue a geographical information system (GIS) and remote sensing (RS) study on roofs factor association with dengue disease by initiating community movement in applyingmosquito net on house ventilations to cut the disease transmission and mosquito breeding sites inside house. Our methods was an operational research in which improvement of interventions, policies and regulations towards dengue disease prevention is our intended endpoint. Several steps were conducted such as: (1) research problems formulation from GIS-RS analysis from previous phase research in Bandung city, (2) informal and formal approach to community leaders and primary healthcare centre (Puskesmas), (3) Video education and focus group discussion (FGD), (4) initial application of mosquito nets on house in communities; and (5) advocacy to Mayor of Bandung city (was on progress).Our study resulted several supports: one of sub-city leaders (Camat) in the city, village leaders (Lurah), and sub-village leaders (Ketua RW) of 5 villages (kelurahan), one kelurahan which mainly comprised formal settlements needed more efforts, which was experts on dengue disease from university to directly explain the mosquito nets application to its community. Informal leaders in all kelurahan’s community suggested only mothers movement was not enough, thus, youths in community was mentioned to help the community movement on the mosquito nets application.

Increases in Recent HIV Testing Among Men Who Have Sex With Men Coincide With the Centers for Disease Control and Prevention's Expanded Testing Initiative

PubMed Central

Cooley, Laura A.; Wejnert, Cyprian; Rose, Charles E.; Paz-Bailey, Gabriela; Taussig, Jennifer; Gern, Robert; Hoyte, Tamika; Salazar, Laura; White, Jianglan; Todd, Jeff; Bautista, Greg; Flynn, Colin; Sifakis, Frangiscos; German, Danielle; Isenberg, Debbie; Driscoll, Maura; Hurwitz, Elizabeth; Doherty, Rose; Wittke, Chris; Prachand, Nikhil; Benbow, Nanette; Melville, Sharon; Pannala, Praveen; Yeager, Richard; Sayegh, Aaron; Dyer, Jim; Sheu, Shane; Novoa, Alicia; Thrun, Mark; Al-Tayyib, Alia; Wilmoth, Ralph; Higgins, Emily; Griffin, Vivian; Mokotoff, Eve; MacMaster, Karen; Wolverton, Marcia; Risser, Jan; Rehman, Hafeez; Padgett, Paige; Bingham, Trista; Sey, Ekow Kwa; LaLota, Marlene; Metsch, Lisa; Forrest, David; Beck, Dano; Cardenas, Gabriel; Nemeth, Chris; Anderson, Bridget J.; Watson, Carol-Ann; Smith, Lou; Robinson, William T.; Gruber, DeAnn; Barak, Narquis; Murrill, Chris; Neaigus, Alan; Jenness, Samuel; Hagan, Holly; Reilly, Kathleen H.; Wendel, Travis; Cross, Helene; Bolden, Barbara; D'Errico, Sally; Wogayehu, Afework; Godette, Henry; Brady, Kathleen A.; Kirkland, Althea; Sifferman, Andrea; Miguelino-Keasling, Vanessa; Velasco, Al; Tovar, Veronica; Raymond, H. Fisher; De León, Sandra Miranda; Rolón-Colón, Yadira; Marzan, Melissa; Courogen, Maria; Jaenicke, Tom; Thiede, Hanne; Burt, Richard; Jia, Yujiang; Opoku, Jenevieve; Sansone, Marie; West, Tiffany; Magnus, Manya; Kuo, Irene

2015-01-01

According to National HIV Behavioral Surveillance system data, human immunodeficiency virus (HIV) testing increased among gay, bisexual, and other men who have sex with men from 2008 to 2011 in cities funded by the Centers for Disease Control and Prevention's Expanded Testing Initiative, suggesting that focused HIV testing initiatives might have positive effects. PMID:25352589

Coronary Revascularization in Children at a Mexican Cardiac Center: Thirteen-Year Outcomes.

PubMed

Ramírez-Marroquín, Samuel E; Iturriaga-Hernández, Alejandra; Calderón-Colmenero, Juan; Benita-Bordes, Antonio; Cervantes-Salazar, Jorge L

2017-09-01

The indications for pediatric coronary revascularization are diverse. There are a large proportion of patients with sequelae of severe inflammatory diseases such as Kawasaki disease, and other less common causes. Retrospective review of ten pediatric patients undergoing coronary artery bypass surgery from January 2004 to December 2016. Ten children and adolescents ranging in age from 2 to 17 (median, 6) years at operation were followed up for as long as 13 years with a median follow-up of 2 years. The surgical indications include ischemia symptoms and/or coronary stenosis angiographically documented. Diagnoses include Kawasaki disease, anomalous origin of the left coronary artery from the pulmonary artery, and iatrogenic lesion of the right coronary artery. All the surgical procedures were performed with cardiopulmonary bypass with crystalloid cardioplegic arrest. The number of distal anastomoses was 1.6 per patient, and the left internal thoracic artery was used in one patient, the right internal thoracic artery in four patients, bilateral internal thoracic artery in four patients, and bilateral internal thoracic artery plus left radial artery in one patient, most frequently for right coronary artery revascularization. The patients underwent noninvasive diagnostic study during follow-up to evaluate their coronary status. The ten patients had no symptoms, and there was no mortality. Although survival was excellent after pediatric coronary bypass in our center, we need to continue the follow-up. Coronary revascularization by means of arterial grafting is a safe and reliable surgical modality for coronary disease in children.

Harnessing the Power of Integrated Mitochondrial Biology and Physiology: A Special Report on the NHLBI Mitochondria in Heart Diseases Initiative

PubMed Central

Ping, Peipei; Gustafsson, Åsa B.; Bers, Don M.; Blatter, Lothar; Cai, Hua; Jahangir, Arshad; Kelly, Daniel; Muoio, Deborah; O'Rourke, Brian; Rabinovitch, Peter; Trayanova, Natalia; Van Eyk, Jennifer; Weiss, James N.; Wong, Renee; Longacre, Lisa Schwartz

2015-01-01

Summary Mitochondrial biology is the sum of diverse phenomena from molecular profiles to physiological functions. A mechanistic understanding of mitochondria in disease development, and hence the future prospect of clinical translations, relies on a systems-level integration of expertise from multiple fields of investigation. Upon the successful completion of a recent National Institutes of Health, National Heart, Lung, and Blood Institute initiative on integrative mitochondrial biology in cardiovascular diseases, we reflect on the accomplishments made possible by this unique interdisciplinary collaboration effort and exciting new fronts on the study of these remarkable organelles. PMID:26185209

The Initial Evaluation of Patients After Positive Newborn Screening: Recommended Algorithms Leading to a Confirmed Diagnosis of Pompe Disease.

PubMed

Burton, Barbara K; Kronn, David F; Hwu, Wuh-Liang; Kishnani, Priya S

2017-07-01

Newborn screening (NBS) for Pompe disease is done through analysis of acid α-glucosidase (GAA) activity in dried blood spots. When GAA levels are below established cutoff values, then second-tier testing is required to confirm or refute a diagnosis of Pompe disease. This article in the "Newborn Screening, Diagnosis, and Treatment for Pompe Disease" guidance supplement provides recommendations for confirmatory testing after a positive NBS result indicative of Pompe disease is obtained. Two algorithms were developed by the Pompe Disease Newborn Screening Working Group, a group of international experts on both NBS and Pompe disease, based on whether DNA sequencing is performed as part of the screening method. Using the recommendations in either algorithm will lead to 1 of 3 diagnoses: classic infantile-onset Pompe disease, late-onset Pompe disease, or no disease/not affected/carrier. Mutation analysis of the GAA gene is essential for confirming the biochemical diagnosis of Pompe disease. For NBS laboratories that do not have DNA sequencing capabilities, the responsibility of obtaining sequencing of the GAA gene will fall on the referral center. The recommendations for confirmatory testing and the initial evaluation are intended for a broad global audience. However, the Working Group recognizes that clinical practices, standards of care, and resource capabilities vary not only regionally, but also by testing centers. Individual patient needs and health status as well as local/regional insurance reimbursement programs and regulations also must be considered. Copyright © 2017 by the American Academy of Pediatrics.

The initiation of metabolic inflammation in childhood obesity.

PubMed

Singer, Kanakadurga; Lumeng, Carey N

2017-01-03

An understanding of the events that initiate metabolic inflammation (metainflammation) can support the identification of targets for preventing metabolic disease and its negative effects on health. There is ample evidence demonstrating that the initiating events in obesity-induced inflammation start early in childhood. This has significant implications on our understanding of how early life events in childhood influence adult disease. In this Review we frame the initiating events of metainflammation in the context of child development and discuss what this reveals about the mechanisms by which this unique form of chronic inflammation is initiated and sustained into adulthood.

The initiation of metabolic inflammation in childhood obesity

PubMed Central

2017-01-01

An understanding of the events that initiate metabolic inflammation (metainflammation) can support the identification of targets for preventing metabolic disease and its negative effects on health. There is ample evidence demonstrating that the initiating events in obesity-induced inflammation start early in childhood. This has significant implications on our understanding of how early life events in childhood influence adult disease. In this Review we frame the initiating events of metainflammation in the context of child development and discuss what this reveals about the mechanisms by which this unique form of chronic inflammation is initiated and sustained into adulthood. PMID:28045405

2014 Update of the Alzheimer's Disease Neuroimaging Initiative: A review of papers published since its inception.

PubMed

Weiner, Michael W; Veitch, Dallas P; Aisen, Paul S; Beckett, Laurel A; Cairns, Nigel J; Cedarbaum, Jesse; Green, Robert C; Harvey, Danielle; Jack, Clifford R; Jagust, William; Luthman, Johan; Morris, John C; Petersen, Ronald C; Saykin, Andrew J; Shaw, Leslie; Shen, Li; Schwarz, Adam; Toga, Arthur W; Trojanowski, John Q

2015-06-01

The Alzheimer's Disease Neuroimaging Initiative (ADNI) is an ongoing, longitudinal, multicenter study designed to develop clinical, imaging, genetic, and biochemical biomarkers for the early detection and tracking of Alzheimer's disease (AD). The initial study, ADNI-1, enrolled 400 subjects with early mild cognitive impairment (MCI), 200 with early AD, and 200 cognitively normal elderly controls. ADNI-1 was extended by a 2-year Grand Opportunities grant in 2009 and by a competitive renewal, ADNI-2, which enrolled an additional 550 participants and will run until 2015. This article reviews all papers published since the inception of the initiative and summarizes the results to the end of 2013. The major accomplishments of ADNI have been as follows: (1) the development of standardized methods for clinical tests, magnetic resonance imaging (MRI), positron emission tomography (PET), and cerebrospinal fluid (CSF) biomarkers in a multicenter setting; (2) elucidation of the patterns and rates of change of imaging and CSF biomarker measurements in control subjects, MCI patients, and AD patients. CSF biomarkers are largely consistent with disease trajectories predicted by β-amyloid cascade (Hardy, J Alzheimer's Dis 2006;9(Suppl 3):151-3) and tau-mediated neurodegeneration hypotheses for AD, whereas brain atrophy and hypometabolism levels show predicted patterns but exhibit differing rates of change depending on region and disease severity; (3) the assessment of alternative methods of diagnostic categorization. Currently, the best classifiers select and combine optimum features from multiple modalities, including MRI, [(18)F]-fluorodeoxyglucose-PET, amyloid PET, CSF biomarkers, and clinical tests; (4) the development of blood biomarkers for AD as potentially noninvasive and low-cost alternatives to CSF biomarkers for AD diagnosis and the assessment of α-syn as an additional biomarker; (5) the development of methods for the early detection of AD. CSF biomarkers, �

The Vietnam Initiative on Zoonotic Infections (VIZIONS): A Strategic Approach to Studying Emerging Zoonotic Infectious Diseases.

PubMed

Rabaa, Maia A; Tue, Ngo Tri; Phuc, Tran My; Carrique-Mas, Juan; Saylors, Karen; Cotten, Matthew; Bryant, Juliet E; Nghia, Ho Dang Trung; Cuong, Nguyen Van; Pham, Hong Anh; Berto, Alessandra; Phat, Voong Vinh; Dung, Tran Thi Ngoc; Bao, Long Hoang; Hoa, Ngo Thi; Wertheim, Heiman; Nadjm, Behzad; Monagin, Corina; van Doorn, H Rogier; Rahman, Motiur; Tra, My Phan Vu; Campbell, James I; Boni, Maciej F; Tam, Pham Thi Thanh; van der Hoek, Lia; Simmonds, Peter; Rambaut, Andrew; Toan, Tran Khanh; Van Vinh Chau, Nguyen; Hien, Tran Tinh; Wolfe, Nathan; Farrar, Jeremy J; Thwaites, Guy; Kellam, Paul; Woolhouse, Mark E J; Baker, Stephen

2015-12-01

The effect of newly emerging or re-emerging infectious diseases of zoonotic origin in human populations can be potentially catastrophic, and large-scale investigations of such diseases are highly challenging. The monitoring of emergence events is subject to ascertainment bias, whether at the level of species discovery, emerging disease events, or disease outbreaks in human populations. Disease surveillance is generally performed post hoc, driven by a response to recent events and by the availability of detection and identification technologies. Additionally, the inventory of pathogens that exist in mammalian and other reservoirs is incomplete, and identifying those with the potential to cause disease in humans is rarely possible in advance. A major step in understanding the burden and diversity of zoonotic infections, the local behavioral and demographic risks of infection, and the risk of emergence of these pathogens in human populations is to establish surveillance networks in populations that maintain regular contact with diverse animal populations, and to simultaneously characterize pathogen diversity in human and animal populations. Vietnam has been an epicenter of disease emergence over the last decade, and practices at the human/animal interface may facilitate the likelihood of spillover of zoonotic pathogens into humans. To tackle the scientific issues surrounding the origins and emergence of zoonotic infections in Vietnam, we have established The Vietnam Initiative on Zoonotic Infections (VIZIONS). This countrywide project, in which several international institutions collaborate with Vietnamese organizations, is combining clinical data, epidemiology, high-throughput sequencing, and social sciences to address relevant one-health questions. Here, we describe the primary aims of the project, the infrastructure established to address our scientific questions, and the current status of the project. Our principal objective is to develop an integrated approach to

2011 Vascular Research Initiatives Conference: basic foundations of translational research in vascular disease.

PubMed

Ziegler, Kenneth R; Dardik, Alan

2011-07-01

The Vascular Research Initiatives Conference (VRIC) is an annual conference organized by the Society for Vascular Surgery (SVS). The 2011 VRIC was held in Chicago (IL, USA) to precede and coincide with the first day of the meeting of the Council on Arteriosclerosis, Thrombosis and Vascular Biology (ATVB) of the American Heart Association. The event is designed to present world class vascular research results, encourage collaboration between vascular surgeons and basic scientists in related disciplines, as well as to stimulate interest in research among aspiring academic vascular surgeons. The 2011 VRIC featured plenary sessions addressing peripheral arterial disease, vascular endothelium and thrombosis, aneurysms, and stem cells and tissue engineering. Recipients of the SVS partner grants with the National Institutes of Health K08 awardees presented their progress reports, and keynote addresses were given by Linda Graham and Frank LoGerfo.

Validation of spot urine in predicting 24-h sodium excretion at the individual level.

PubMed

Zhou, Long; Tian, Yu; Fu, Jun-Jie; Jiang, Ying-Ying; Bai, Ya-Min; Zhang, Zi-Hua; Hu, Xiao-He; Lian, Hong-Wu; Guo, Min; Yang, Zheng-Xiong; Zhao, Lian-Cheng

2017-06-01

Background: Evidence for the effect of dietary sodium intake on the risk of cardiovascular disease has been controversial. One of the main explanations for the conflicting results lies in the great variability associated with measurement methods for sodium intake. Spot urine collection is a convenient method commonly used for sodium estimation, but its validity for predicting 24-h urinary sodium excretion at the individual level has not been well evaluated among the general population. Objective: The aim of this study was to evaluate the validity of the Kawasaki, the International Cooperative Study on Salt, Other Factors, and Blood Pressure (INTERSALT), and the Tanaka formulas in predicting 24-h urinary sodium excretion by using spot urine samples in Chinese adults. Design: We analyzed the relative and absolute differences and misclassification at the individual level from 3 commonly used methods for estimating sodium intake among 141 Chinese community residents. Results: The mean measured 24-h sodium excretion was 220.8 mmol/d. The median (95% CIs) differences between measured sodium and those estimated from the Kawasaki, INTERSALT, and Tanaka methods were 6.4 mmol/d (-17.5, 36.8 mmol/d), -67.3 mmol/d (-96.5, -46.9 mmol/d), and -42.9 mmol/d (-59.1, -24.8 mmol/d), respectively. The proportions of relative differences >40% with the Kawasaki, INTERSALT, and Tanaka methods were 31.2%, 41.1%, and 22.0%, respectively; and the absolute difference for the 3 methods was >51.3 mmol/d (3 g salt) in approximately half of the participants. The misclassification rate was 63.1% for the Kawasaki method, 78.7% for the INTERSALT method, and 66.0% for the Tanaka method at the individual level. Conclusion: The results from our study do not support the use of spot urine to estimate 24-h urinary sodium excretion at the individual level because of its poor performance with respect to misclassification. This trial was registered at www.chictr.org.cn as ChiCTR-IOR-16010278. © 2017

Aqueous and organic extract of PM2.5 collected in different seasons and cities of Japan differently affect respiratory and immune systems.

PubMed

Chowdhury, Pratiti Home; Okano, Hitoshi; Honda, Akiko; Kudou, Hitomi; Kitamura, Gaku; Ito, Sho; Ueda, Kayo; Takano, Hirohisa

2018-04-01

Particulate matter with diameters <2.5 μm (i.e., PM 2.5 ) has multiple natural and anthropological sources. The association between PM 2.5 and the exacerbation of respiratory allergy and asthma has been well studied, but the components of PM 2.5 that are responsible for allergies have not yet been determined. Here, we elucidated the effects of aqueous and organic extract of PM 2.5 collected during four seasons in November 2014-December 2015 in two cities (Kawasaki, an industrial area and Fukuoka, an urban area affected by transboundary pollution matter) of Japan on respiratory health. Ambient PM 2.5 was collected by high-volume air samplers and extracted into water soluble and lipid soluble components. Human airway epithelial cells, murine bone marrow-derived antigen-presenting cells (APC) and splenocytes were exposed to PM 2.5 extracts. We measured the cell viability and release of interleukin (IL)-6 and IL-8 from airway epithelial cells, the DEC205 and CD86 expressions on APCs and cell proliferation, and TCR and CD19 expression on splenocytes. The water-soluble or aqueous extracts, especially those from Kawasaki in fall, had a greater cytotoxic effect than the lipid-soluble or organic extracts in airway epithelial cells, but they caused almost no pro-inflammatory response. Extract of fall, especially the aqueous extract from Fukuoka, increased the DEC205 and CD86 expressions on APC. Moreover, aqueous extracts of fall, summer, and spring from Fukuoka significantly increased proliferation of splenocytes. Organic extract of spring and summer from Kawasaki significantly elevated the TCR expression, and organic extract of summer from Kawasaki decreased the CD19 expression. These results suggest that PM 2.5 extract samples are responsible for cytotoxicity in airway epithelial cells and for activating APCs and T-cells, which can contribute to the exacerbation of respiratory diseases such as asthma. These effects can differ by PM 2.5 components, collection areas and

ANTICIPATORY POSTURAL ADJUSTMENTS PRIOR TO STEP INITIATION ARE HYPOMETRIC IN UNTREATED PARKINSON'S DISEASE: AN ACCELEROMETER-BASED APPROACH

PubMed Central

Mancini, Martina; Zampieri, Cris; Carlson-Kuhta, Patricia; Chiari, Lorenzo; Horak, Fay B.

2010-01-01

Background and purpose Anticipatory postural adjustments (APAs), prior to step initiation, are bradykinetic in advanced Parkinson's disease (PD) and may be one of the factors associated with ‘start hesitation’. However, little is known about APAs in the early stage of PD. In this study, we determined whether body-worn accelerometers could be used to characterize step initiation deficits in subjects with early-to-moderate, untreated PD. Methods Eleven PD and 12 healthy control subjects were asked to take two steps. Postural adjustments were compared from center of pressure (COP) and from acceleration of the trunk at the center of mass level (L5). Results Our findings show that APAs measured from the peak COP displacement towards the swing leg and the peak trunk acceleration towards the stance leg were smaller in untreated PD compared to control subjects. The magnitude of APAs measured from peak COP displacements and accelerations were correlated. Conclusion These results suggest that quantitative analysis of step initiation from one accelerometer on the trunk could provide useful information for the characterization of patients in early stages of PD, when clinical evidence of start hesitation may not be detectable. Ambulatory monitoring of step initiation is also promising for monitoring patient progression in the home environment, and eventually providing feedback for preventing freezing of gait episodes. PMID:19473350

Heart Rate and Initial Presentation of Cardiovascular Diseases (Caliber)

ClinicalTrials.gov

2013-09-17

Abdominal Aortic Aneurysm; Coronary Heart Disease NOS; Unheralded Coronary Death; Intracerebral Haemorrhage; Heart Failure; Ischemic Stroke; Myocardial Infarction; Stroke; Peripheral Arterial Disease; Stable Angina Pectoris; Subarachnoid Haemorrhage; Transient Ischemic Attack; Unstable Angina; Cardiac Arrest, Sudden Cardiac Death

Harnessing the Power of Integrated Mitochondrial Biology and Physiology: A Special Report on the NHLBI Mitochondria in Heart Diseases Initiative.

PubMed

Ping, Peipei; Gustafsson, Åsa B; Bers, Don M; Blatter, Lothar A; Cai, Hua; Jahangir, Arshad; Kelly, Daniel; Muoio, Deborah; O'Rourke, Brian; Rabinovitch, Peter; Trayanova, Natalia; Van Eyk, Jennifer; Weiss, James N; Wong, Renee; Schwartz Longacre, Lisa

2015-07-17

Mitochondrial biology is the sum of diverse phenomena from molecular profiles to physiological functions. A mechanistic understanding of mitochondria in disease development, and hence the future prospect of clinical translations, relies on a systems-level integration of expertise from multiple fields of investigation. Upon the successful conclusion of a recent National Institutes of Health, National Heart, Lung, and Blood Institute initiative on integrative mitochondrial biology in cardiovascular diseases, we reflect on the accomplishments made possible by this unique interdisciplinary collaboration effort and exciting new fronts on the study of these remarkable organelles. © 2015 American Heart Association, Inc.

Points to consider for reporting, screening for and preventing selected comorbidities in chronic inflammatory rheumatic diseases in daily practice: a EULAR initiative.

PubMed

Baillet, Athan; Gossec, Laure; Carmona, Loreto; Wit, Maarten de; van Eijk-Hustings, Yvonne; Bertheussen, Heidi; Alison, Kent; Toft, Mette; Kouloumas, Marios; Ferreira, Ricardo J O; Oliver, Susan; Rubbert-Roth, Andrea; van Assen, Sander; Dixon, William G; Finckh, Axel; Zink, Angela; Kremer, Joel; Kvien, Tore K; Nurmohamed, Michael; van der Heijde, Desirée; Dougados, Maxime

2016-06-01

In chronic inflammatory rheumatic diseases, comorbidities such as cardiovascular diseases and infections are suboptimally prevented, screened for and managed. The objective of this European League Against Rheumatism (EULAR) initiative was to propose points to consider to collect comorbidities in patients with chronic inflammatory rheumatic diseases. We also aimed to develop a pragmatic reporting form to foster the implementation of the points to consider. In accordance with the EULAR Standardised Operating Procedures, the process comprised (1) a systematic literature review of existing recommendations on reporting, screening for or preventing six selected comorbidities: ischaemic cardiovascular diseases, malignancies, infections, gastrointestinal diseases, osteoporosis and depression and (2) a consensus process involving 21 experts (ie, rheumatologists, patients, health professionals). Recommendations on how to treat the comorbidities were not included in the document as they vary across countries. The literature review retrieved 42 articles, most of which were recommendations for reporting or screening for comorbidities in the general population. The consensus process led to three overarching principles and 15 points to consider, related to the six comorbidities, with three sections: (1) reporting (ie, occurrence of the comorbidity and current treatments); (2) screening for disease (eg, mammography) or for risk factors (eg, smoking) and (3) prevention (eg, vaccination). A reporting form (93 questions) corresponding to a practical application of the points to consider was developed. Using an evidence-based approach followed by expert consensus, this EULAR initiative aims to improve the reporting and prevention of comorbidities in chronic inflammatory rheumatic diseases. Next steps include dissemination and implementation. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Scottish Asthma Management Initiative.

PubMed

Hoskins, G; Neville, R G; McCowan, C; Smith, B; Clark, R A; Ricketts, I W

2000-11-01

To describe the development process of a system that links audit, research and patient care and to detail the lessons learned from establishing a Scotland wide asthma management initiative. Health Boards and practices throughout Scotland were invited to participate in an initiative which links review of care, guideline implementation, chronic disease management (CDM) approval and post-graduate education for doctors (PGEA) and nurses (PREP). Participating practices were given the materials to review 30 patients randomly selected from their asthma register. Health service resource use and drugs prescribed over a retrospective 12 month period were recorded for each patient using paper or electronic materials. All patients were invited for clinical assessment. A two-tier management system proved effective. Twelve of the 15 Scottish health authorities agreed to recognise the audit for automatic CDM approval although the negotiation process was prolonged; 566 practices from all parts of Scotland have expressed an interest in the initiative. Provision of distance learning material linked to PGEA accreditation is free to general practitioners (GP's) and is a useful incentive for participation. To date 42 GPs have completed the distance learning element. The Scottish Asthma Management Initiative has provided the opportunity for all sectors of the health service in Scotland to work together to explore innovative ways to improve the management and care of chronic disease. Participation in an initiative linked to guidelines, education and CDM approval is an excellent way to facilitate health professionals to improve care.

Global cancer research initiative

PubMed Central

Love, Richard R

2010-01-01

Cancer is an increasing problem for low- and middle-income countries undergoing an epidemiologic transition from dominantly acute communicable disease to more frequent chronic disease with increased public health successes in the former domain. Progress against cancer in high-income countries has been modest and has come at enormous expense. There are several well-conceived global policy and planning initiatives which, with adequate political will, can favorably impact the growing global cancer challenges. Most financial resources for cancer, however, are spent on diagnosis and management of patients with disease in circumstances where specific knowledge about effective approaches is significantly limited, and the majority of interventions, other than surgery, are not cost-effective in resource-limited countries by global standards. In summary, how to intervene effectively on a global scale for the majority of citizens who develop cancer is poorly defined. In contrast to technology-transfer approaches, markedly increased clinical research activities are more likely to benefit cancer sufferers. In these contexts, a global cancer research initiative is proposed, and mechanisms for realizing such an effort are suggested. PMID:21188101

Neutrophil Counts and Initial Presentation of 12 Cardiovascular Diseases: A CALIBER Cohort Study.

PubMed

Shah, Anoop Dinesh; Denaxas, Spiros; Nicholas, Owen; Hingorani, Aroon D; Hemingway, Harry

2017-03-07

Neutrophil counts are a ubiquitous measure of inflammation, but previous studies on their association with cardiovascular disease (CVD) were limited by small numbers of patients or a narrow range of endpoints. This study investigated associations of clinically recorded neutrophil counts with initial presentation for a range of CVDs. We used linked primary care, hospitalization, disease registry, and mortality data in England. We included people 30 years or older with complete blood counts performed in usual clinical care and no history of CVD. We used Cox models to estimate cause-specific hazard ratios (HRs) for 12 CVDs, adjusted for cardiovascular risk factors and acute conditions affecting neutrophil counts (such as infections and cancer). Among 775,231 individuals in the cohort, 154,179 had complete blood counts performed under acute conditions and 621,052 when they were stable. Over a median 3.8 years of follow-up, 55,004 individuals developed CVD. Adjusted HRs comparing neutrophil counts 6 to 7 versus 2 to 3 × 10 9 /l (both within the 'normal' range) showed strong associations with heart failure (HR: 2.04; 95% confidence interval [CI]: 1.82 to 2.29), peripheral arterial disease (HR: 1.95; 95% CI: 1.72 to 2.21), unheralded coronary death (HR: 1.78; 95% CI: 1.51 to 2.10), abdominal aortic aneurysm (HR: 1.72; 95% CI: 1.34 to 2.21), and nonfatal myocardial infarction (HR: 1.58; 95% CI: 1.42 to 1.76). These associations were linear, with greater risk even among individuals with neutrophil counts of 3 to 4 versus 2 to 3 × 10 9 /l. There was a weak association with ischemic stroke (HR: 1.36; 95% CI: 1.17 to 1.57), but no association with stable angina or intracerebral hemorrhage. Neutrophil counts were strongly associated with the incidence of some CVDs, but not others, even within the normal range, consistent with underlying disease mechanisms differing across CVDs. (White Blood Cell Counts and Onset of Cardiovascular Diseases: a CALIBER Study [CALIBER]; NCT

Rhabdomyolysis associated with initiation of febuxostat therapy for hyperuricaemia in a patient with chronic kidney disease.

PubMed

Kang, Y; Kim, M J; Jang, H N; Bae, E J; Yun, S; Cho, H S; Chang, S-H; Park, D J

2014-06-01

Febuxostat is now recommended as the first-line pharmacological urate-lowering therapy for gout in the American College of Rheumatology guidelines. There is no case of rhabdomyolysis associated with febuxostat among reported side effects of the drug. Our objective is to report on a case of rhabdomyolysis associated with initiation of febuxostat in a patient with chronic kidney disease (CKD). A 73-year-old male patient visited our emergency room due to progressive weakness in both lower extremities starting 3 days earlier. Ten days before presentation, his primary physician had changed his prescription from allopurinol to febuxostat (80 mg) because of poor control of uric acid levels. There was tenderness in both thighs. Initial creatinine kinase (CK) was 7652 U/L (0-170 U/L), and a bone scan using (99m) Tc-HDP revealed strong uptake in soft tissues in both thighs and buttocks. Electromyography (EMG) and nerve conduction velocity (NCV) showed abnormal spontaneous activities (ASA), suggesting myopathy, not nerve damage. On day 7 of admission, after conservative management and febuxostat withdrawal, he could walk on the ward. He is being followed in our clinic as an outpatient with no sequelae. This report is first case of rhabdomyolysis associated with initiation of febuxostat. Febuxostat should be withdrawn when rhabdomyolysis is confirmed. © 2014 John Wiley & Sons Ltd.

WSU-IR at TREC 2015 Clinical Decision Support Track: Joint Weighting of Explicit and Latent Medical Query Concepts from Diverse Sources

DTIC Science & Technology

2015-11-20

noticed erythematous rash on the girl’s trunk. Physical examination reveals strawberry red tongue, red and cracked lips, and swollen red hands. The whites...as erythematous rash, and test results, such as revealed swollen red hands and strawberry red tongue, as well as indicates a possible di- agnosis...such as strawberry tongue (also known as Kawasaki disease). Although such queries are fairly long, only a fraction of concepts corresponding to an in

Risk Factors for Initiation of Potentially Inappropriate Medications in Community-Dwelling Older Adults with and without Alzheimer's Disease.

PubMed

Hyttinen, Virva; Taipale, Heidi; Tanskanen, Antti; Tiihonen, Jari; Tolppanen, Anna-Maija; Hartikainen, Sirpa; Valtonen, Hannu

2017-01-01

Various criteria have been created to define potentially inappropriate medications (PIMs) to help improve the quality and safety of medicine use in older patients. Individuals with Alzheimer's disease (AD) may be at higher risk of adverse drug events associated with PIMs (such as falls). Our objective was to determine the risk factors for PIM initiation in a nationwide cohort of community dwellers aged ≥65 years with and without AD. The Finnish nationwide MEDALZ cohort includes all patients diagnosed with AD in 2005-2011 (n = 70,718) and two comparison individuals without AD (non-AD) matched for age, sex and region of residence for each person with AD. After a 1-year washout period for PIM use and exclusion of those aged <65 years, we included 50,494 patients with AD and 106,306 comparison subjects. PIM use was defined according to Finnish criteria. Subjects without AD initiated PIMs more frequently than those with AD (16.4 vs. 12.2%, respectively; p < 0.001). The most common PIMs were muscle relaxants and urinary antispasmodics. Older individuals (aged ≥75 years) were less likely to initiate PIMs. In the AD group, women were less likely to initiate PIMs than men. More comorbidities were associated with PIM initiation, especially in the non-AD group. The use of opioids or psychotropic medicines was associated with PIM initiation in both cohorts. Regional differences between university hospital districts were observed. PIM initiation was dependent on patient characteristics and possibly also some healthcare system-related factors such as differing regional treatment practices. It is important that medicines prescribed to the older vulnerable population are assessed regularly to avoid adverse effects and ensure safe pharmacotherapy, especially in those with multiple comorbidities.

2014 Update of the Alzheimer’s Disease Neuroimaging Initiative: A review of papers published since its inception

PubMed Central

Weiner, Michael W.; Veitch, Dallas P.; Aisen, Paul S.; Beckett, Laurel A.; Cairns, Nigel J.; Cedarbaum, Jesse; Green, Robert C.; Harvey, Danielle; Jack, Clifford R.; Jagust, William; Luthman, Johan; Morris, John C.; Petersen, Ronald C.; Saykin, Andrew J.; Shaw, Leslie; Shen, Li; Schwarz, Adam; Toga, Arthur W.; Trojanowski, John Q.

2016-01-01

The Alzheimer’s Disease Neuroimaging Initiative (ADNI) is an ongoing, longitudinal, multicenter study designed to develop clinical, imaging, genetic, and biochemical biomarkers for the early detection and tracking of Alzheimer’s disease (AD). The initial study, ADNI-1, enrolled 400 subjects with early mild cognitive impairment (MCI), 200 with early AD, and 200 cognitively normal elderly controls. ADNI-1 was extended by a 2-year Grand Opportunities grant in 2009 and by a competitive renewal, ADNI-2, which enrolled an additional 550 participants and will run until 2015. This article reviews all papers published since the inception of the initiative and summarizes the results to the end of 2013. The major accomplishments of ADNI have been as follows: (1) the development of standardized methods for clinical tests, magnetic resonance imaging (MRI), positron emission tomography (PET), and cerebrospinal fluid (CSF) biomarkers in a multicenter setting; (2) elucidation of the patterns and rates of change of imaging and CSF biomarker measurements in control subjects, MCI patients, and AD patients. CSF biomarkers are largely consistent with disease trajectories predicted by β-amyloid cascade (Hardy, J Alzheimer’s Dis 2006;9(Suppl 3):151–3) and tau-mediated neurodegeneration hypotheses for AD, whereas brain atrophy and hypometabolism levels show predicted patterns but exhibit differing rates of change depending on region and disease severity; (3) the assessment of alternative methods of diagnostic categorization. Currently, the best classifiers select and combine optimum features from multiple modalities, including MRI, [18F]-fluorodeoxyglucose-PET, amyloid PET, CSF biomarkers, and clinical tests; (4) the development of blood biomarkers for AD as potentially noninvasive and low-cost alternatives to CSF biomarkers for AD diagnosis and the assessment of α-syn as an additional biomarker; (5) the development of methods for the early detection of AD. CSF biomarkers, �

CATEGORICAL AND CORRELATIONAL ANALYSES OF BASELINE FLUORODEOXYGLUCOSE POSITRON EMISSION TOMOGRAPHY IMAGES FROM THE ALZHEIMER’S DISEASE NEUROIMAGING INITIATIVE (ADNI)

PubMed Central

Langbaum, Jessica B.S.; Chen, Kewei; Lee, Wendy; Reschke, Cole; Bandy, Dan; Fleisher, Adam S.; Alexander, Gene E.; Foster, Norman L.; Weiner, Michael W.; Koeppe, Robert A.; Jagust, William J.; Reiman, Eric M.

2010-01-01

In mostly small single-center studies, Alzheimer’s disease (AD) is associated with characteristic and progressive reductions in fluorodeoxyglucose positron emission tomography (PET) measurements of the regional cerebral metabolic rate for glucose (CMRgl). The AD Neuroimaging Initiative (ADNI) is acquiring FDG PET, volumetric magnetic resonance imaging, and other biomarker measurements in a large longitudinal multi-center study of initially mildly affected probable AD (pAD) patients, amnestic mild cognitive impairment (aMCI) patients, who are at increased AD risk, and cognitively normal controls (NC), and we are responsible for analyzing the PET images using statistical parametric mapping (SPM). Here we compare baseline CMRgl measurements from 74 pAD patients and 142 aMCI patients to those from 82 NC, we correlate CMRgl with categorical and continuous measures of clinical disease severity, and we compare apolipoprotein E (APOE) ε4 carriers to non-carriers in each of these subject groups. In comparison with NC, the pAD and aMCI groups each had significantly lower CMRgl bilaterally in posterior cingulate, precuneus, parietotemporal and frontal cortex. Similar reductions were observed when categories of disease severity or lower Mini-Mental State Exam (MMSE) scores were correlated with lower CMRgl. However, when analyses were restricted to the pAD patients, lower MMSE scores were significantly correlated with lower left frontal and temporal CMRgl. These findings from a large, multi-site study support previous single-site findings, supports the characteristic pattern of baseline CMRgl reductions in AD and aMCI patients, as well as preferential anterior CMRgl reductions after the onset of AD dementia. PMID:19349228

Validation and Assessment of Three Methods to Estimate 24-h Urinary Sodium Excretion from Spot Urine Samples in High-Risk Elder Patients of Stroke from the Rural Areas of Shaanxi Province

PubMed Central

Ma, Wenxia; Yin, Xuejun; Zhang, Ruijuan; Liu, Furong; Yang, Danrong; Fan, Yameng; Rong, Jie; Tian, Maoyi; Yu, Yan

2017-01-01

Background: 24-h urine collection is regarded as the “gold standard” for monitoring sodium intake at the population level, but ensuring high quality urine samples is difficult to achieve. The Kawasaki, International Study of Sodium, Potassium, and Blood Pressure (INTERSALT) and Tanaka methods have been used to estimate 24-h urinary sodium excretion from spot urine samples in some countries, but few studies have been performed to compare and validate these methods in the Chinese population. Objective: To compare and validate the Kawasaki, INTERSALT and Tanaka formulas in predicting 24-h urinary sodium excretion using spot urine samples in 365 high-risk elder patients of strokefrom the rural areas of Shaanxi province. Methods: Data were collected from a sub-sample of theSalt Substitute and Stroke Study. 365 high-risk elder patients of stroke from the rural areas of Shaanxi province participated and their spot and 24-h urine specimens were collected. The concentrations of sodium, potassium and creatinine in spot and 24-h urine samples wereanalysed. Estimated 24-h sodium excretion was predicted from spot urine concentration using the Kawasaki, INTERSALT, and Tanaka formulas. Pearson correlation coefficients and agreement by Bland-Altman method were computed for estimated and measured 24-h urinary sodium excretion. Results: The average 24-h urinary sodium excretion was 162.0 mmol/day, which representing a salt intake of 9.5 g/day. Three predictive equations had low correlation with the measured 24-h sodium excretion (r = 0.38, p < 0.01; ICC = 0.38, p < 0.01 for the Kawasaki; r = 0.35, p < 0.01; ICC = 0.31, p < 0.01 for the INTERSALT; r = 0.37, p < 0.01; ICC = 0.34, p < 0.01 for the Tanaka). Significant biases between estimated and measured 24-h sodium excretion were observed (all p < 0.01 for three methods). Among the three methods, the Kawasaki method was the least biased compared with the other two methods (mean bias: 31.90, 95% Cl: 23.84, 39.97). Overestimation

Validation and Assessment of Three Methods to Estimate 24-h Urinary Sodium Excretion from Spot Urine Samples in High-Risk Elder Patients of Stroke from the Rural Areas of Shaanxi Province.

PubMed

Ma, Wenxia; Yin, Xuejun; Zhang, Ruijuan; Liu, Furong; Yang, Danrong; Fan, Yameng; Rong, Jie; Tian, Maoyi; Yu, Yan

2017-10-11

Background : 24-h urine collection is regarded as the "gold standard" for monitoring sodium intake at the population level, but ensuring high quality urine samples is difficult to achieve. The Kawasaki, International Study of Sodium, Potassium, and Blood Pressure (INTERSALT) and Tanaka methods have been used to estimate 24-h urinary sodium excretion from spot urine samples in some countries, but few studies have been performed to compare and validate these methods in the Chinese population. Objective : To compare and validate the Kawasaki, INTERSALT and Tanaka formulas in predicting 24-h urinary sodium excretion using spot urine samples in 365 high-risk elder patients of strokefrom the rural areas of Shaanxi province. Methods : Data were collected from a sub-sample of theSalt Substitute and Stroke Study. 365 high-risk elder patients of stroke from the rural areas of Shaanxi province participated and their spot and 24-h urine specimens were collected. The concentrations of sodium, potassium and creatinine in spot and 24-h urine samples wereanalysed. Estimated 24-h sodium excretion was predicted from spot urine concentration using the Kawasaki, INTERSALT, and Tanaka formulas. Pearson correlation coefficients and agreement by Bland-Altman method were computed for estimated and measured 24-h urinary sodium excretion. Results : The average 24-h urinary sodium excretion was 162.0 mmol/day, which representing a salt intake of 9.5 g/day. Three predictive equations had low correlation with the measured 24-h sodium excretion (r = 0.38, p < 0.01; ICC = 0.38, p < 0.01 for the Kawasaki; r = 0.35, p < 0.01; ICC = 0.31, p < 0.01 for the INTERSALT; r = 0.37, p < 0.01; ICC = 0.34, p < 0.01 for the Tanaka). Significant biases between estimated and measured 24-h sodium excretion were observed (all p < 0.01 for three methods). Among the three methods, the Kawasaki method was the least biased compared with the other two methods (mean bias: 31.90, 95% Cl: 23.84, 39.97). Overestimation

Medication for Alzheimer's disease and associated fall hazard: a retrospective cohort study from the Alzheimer's Disease Neuroimaging Initiative.

PubMed

Epstein, Noam U; Guo, Rong; Farlow, Martin R; Singh, Jaswinder P; Fisher, Morris

2014-02-01

Falls are common in the elderly, especially in those with cognitive impairment. The elderly are often treated with several medications, which may have both beneficial and deleterious effects. The use and type of medication in Alzheimer's disease (AD) patients and association with falls is limited. We examined the association between falls and medication use in the Alzheimer's Disease Neuroimaging Initiative (ADNI). Diagnosis, demographics, medication use, apolipoprotein E4 allele status and functional activity level at baseline were gathered for 810 participants enrolled in the ADNI, including healthy controls and subjects with mild cognitive impairment or Alzheimer's. Reports detailing adverse event falls were tabulated. Baseline characteristics were compared between subjects with and without one or more falls. Cox proportional hazards models were conducted to evaluate the association between subject characteristics and hazard of the first fall. Age (p < 0.0001), Functional Activities Questionnaire (p = 0.035), Beers List (p = 0.0477) and medications for treating cognitive symptoms of Alzheimer's (p = 0.0019) were associated with hazard of fall in the univariate model. In the final multivariate model, after adjusting for covariates, Alzheimer's medication use (p = 0.0005) was associated with hazard of fall. Medication was changed by the clinician after an adverse fall event in 9% of the falls. About 7% of the falls were reported as serious adverse events and 6% were reported to be severe. We found a significant association between the use of symptomatic medication treating cognitive symptoms in AD and hazard of fall after adjusting for age and Beers List medication use. Additional pharmacovigilance of the association between falls and Alzheimer's medication use is warranted.

RotaTeq vaccine adverse events and policy considerations.

PubMed

Geier, David A; King, Paul G; Sykes, Lisa K; Geier, Mark R

2008-03-01

Rotavirus is the leading cause of severe gastroenteritis in children <5 years-old worldwide. On February 3, 2006, the US Food and Drug Administration licensed RotaTeq (Merck and Co.), a bioengineered combination of five human-bovine hybridized reassortment rotaviruses. In August of 2006, the Advisory Committee on Immunization Practices recommended RotaTeq for routine vaccination of US infants administered orally at the ages 2, 4, and 6 months. An evaluation of data reported to VAERS following the first five quarters of post-marketing surveillance of RotaTeq was undertaken. Trends in adverse events reported following RotaTeq and cost-effectiveness calculations of RotaTeq in the context of the disease burden of rotavirus in the US were examined. From February 3, 2006 through July 31, 2007, a total of 160 (of the 165 reported) intussusception and 11 (of the 16 reported) Kawasaki disease adverse event reports were identified when RotaTeq was administered or co-administered with other vaccines. Time-trend analyses showed that there were significant increases in the total number of intussusception and Kawasaki disease adverse events entered into VAERS in comparison to previous years. These observations, coupled with limited rotavirus disease burden, cost-effectiveness, and potential contact viral transmission concerns, raise serious questions regarding the use of RotaTeq in the US. Healthcare providers should diligently report adverse events following RotaTeq vaccination to VAERS, and those who have experienced a vaccine-associated adverse event should be made aware that they may be eligible for compensation from the no-fault National Vaccine Injury Compensation Program (NVICP).

Virtual angioscopic visualization and analysis of coronary aneurysms using intravascular ultrasound images

NASA Astrophysics Data System (ADS)

Ayeni, Tina A.; Holmes, David R., III; Robb, Richard A.

2001-05-01

Kawasaki Disease is an inflammatory illness of young children that can seriously affect the cardiovascular system. The disease may cause coronary artery aneurysms, a thinning and dilation of the arterial wall when the wall is weakened by disease. Such aneurysms significantly increase the risk of rupture of the arterial wall, an event from which few patients survive. Due to the largely asymptotic nature of coronary aneurysms, diagnosis must be timely and accurate in order for treatment to be effective. Currently, aneurysms are detected primarily using X-ray angiography, MRI, and CT images. Increased insight into the disease and its effects on the arterial wall can be gained by multi-dimensional computerized visualization and quantitative analysis of diagnostic images made possible by the techniques of intravascular imaging and virtual endoscopy. Intravascular ultrasound images (IVUS) of a coronary artery exhibiting aneurysms were acquired from a patient with Kawasaki Disease. The disease is characterized by low luminescent in the IVUS images. Image segmentation of the abnormal, prominent anechoic regions branching from the lumen and originating within other layers of the arterial wall was performed and each region defined as a separate object. An object segmentation map was generated and used in perspective rendering of the original image volume set at successive locations along the length of the arterial segment, producing a 'fly-through' of the interior of the artery. The diseased region (aneurysm) of the wall was well defined by the differences in luminal size and by differences in appearance of the arterial wall shape observed during virtual angioscopic fly-throughs. Erosions of the endovascular surface caused pronounced horizontal and vertical ballooning of the lumen. Minute cracks within the unaffected luminal areas revealed possible early development of an aneurysm on the contralateral wall, originating in the medial section of the artery and spreading

Patients' perception of Parkinson's disease-associated pain following initiation of rotigotine: a multicenter non-interventional study.

PubMed

Timmermann, Lars; Oehlwein, Christian; Ransmayr, Gerhard; Fröhlich, Holger; Will, Edgar; Schroeder, Hanna; Lauterbach, Thomas; Bauer, Lars; Kassubek, Jan

2017-01-01

To evaluate Parkinson's disease (PD)-associated pain as perceived by the patients (subjective characterization), and how this may change following initiation of rotigotine transdermal patch. SP1058 was a non-interventional study conducted in routine clinical practice in Germany and Austria in patients experiencing PD-associated pain (per the physician's assessment). Data were collected at baseline (ie, before rotigotine initiation) and at a routine visit after ≥25 days (-3 days allowed) of treatment on a maintenance dose of rotigotine (end of study [EoS]). Pain perception was assessed using the 12-item Pain Description List of the validated German Pain Questionnaire (each item ranked 0 = 'not true' to 3 = 'very true'). Primary effectiveness variable: change from baseline to EoS in the sum score of the 4 'affective dimension' items of the Pain Description List. Secondary effectiveness variables: change from baseline to EoS in Unified Parkinson's Disease Rating Scale (UPDRS) II, III, and II+III scores, and Parkinson's Disease Questionnaire (PDQ-8) total score (PD-related quality-of-life). Other variables included scores of the eight 'sensory dimension' items of the Pain Description List. Of 93 enrolled patients (mean [SD] age: 71.1 [9.0] years; male: 48 [52%]), 77 (83%) completed the study, and 70 comprised the full analysis set. The mean (SD) change from baseline in the sum score of the four 'affective dimension' items was -1.3 (2.8) indicating a numerical improvement (baseline: 3.9 [3.4]). In the 'sensory dimension', pain was mostly perceived as 'pulling' at baseline (49/70 [70%]); 'largely true'/'very true'). Numerical improvements were observed in all UPDRS scores (mean [SD] change in UPDRS II+III: -5.3 [10.5]; baseline: 36.0 [15.9]), and in PDQ-8 total score (-2.0 [4.8]; baseline: 10.7 [5.9]). Adverse drug reactions were consistent with dopaminergic stimulation and transdermal administration. The perception of the 'affective dimension' of PD

Treatment With Cholinesterase Inhibitors and Memantine of Patients in the Alzheimer’s Disease Neuroimaging Initiative

PubMed Central

Schneider, Lon S.; Insel, Philip S.; Weiner, Michael W.

2011-01-01

Objectives To assess the clinical characteristics and course of patients with mild cognitive impairment (MCI) and mild Alzheimer disease (AD) treated with cholinesterase inhibitors (ChEIs) and memantine hydrochloride. Design Cohort study. Setting The 59 recruiting sites for the Alzheimer’s Disease Neuroimaging Initiative (ADNI). Participants Outpatients with MCI and AD in ADNI. Main Outcome Measures The AD Assessment Scale–cognitive subscale (ADAS-cog), Mini-Mental State Examination (MMSE), Clinical Dementia Rating (CDR) scale, and Functional Activities Questionnaire (FAQ). Results A total of 177 (44.0%) of 402 MCI patients and 159 (84.6%) of 188 mild-AD patients were treated with ChEIs and 11.4% of MCI patients and 45.7% of AD patients with memantine at entry. Mild-cognitive-impairment patients who received ChEIs with or without memantine were more impaired, showed greater decline in scores, and progressed to dementia sooner than patients who did not receive ChEIs. Alzheimer-disease patients who received ChEIs and memantine took them longer, were more functionally impaired, and showed greater decline on the MMSE and CDR (but not on the ADAS-cog or FAQ) than those who received ChEIs only. Conclusions Academic physicians frequently prescribe ChEIs and memantine earlier than indicated in the US Food and Drug Administration–approved labeling to patients who are relatively more severely impaired or who are rapidly progressing toward cognitive impairment. The use of these medications in ADNI is associated with clinical decline and may affect the interpretation of clinical trial outcomes. Study Registration clinicalTrials.gov Identifier: NCT00106899 PMID:21220675

CSF biomarkers associated with disease heterogeneity in early Parkinson’s disease: the Parkinson’s Progression Markers Initiative study

PubMed Central

Kang, Ju-Hee; Mollenhauer, Brit; Coffey, Christopher S.; Toledo, Jon B.; Weintraub, Daniel; Galasko, Douglas R.; Irwin, David J.; Van Deerlin, Vivianna; Chen-Plotkin, Alice S.; Caspell-Garcia, Chelsea; Waligórska, Teresa; Taylor, Peggy; Shah, Nirali; Pan, Sarah; Zero, Pawel; Frasier, Mark; Marek, Kenneth; Kieburtz, Karl; Jennings, Danna; Tanner, Caroline M.; Simuni, Tanya; Singleton, Andrew; Toga, Arthur W.; Chowdhury, Sohini; Trojanowski, John Q.; Shaw, Leslie M.

2016-01-01

The development of biomarkers to predict the progression of Parkinson’s disease (PD) from its earliest stage through its heterogeneous course is critical for research and therapeutic development. The Parkinson’s Progression Markers Initiative (PPMI) study is an ongoing international multicenter, prospective study to validate biomarkers in drug-naïve PD patients and matched healthy controls (HC). We quantified cerebrospinal fluid (CSF) alpha-synuclein (α-syn), amyloid-beta1–42 (Aβ1–42), total tau (t-tau), and tau phosphorylated at Thr181 (p-tau) in 660 PPMI subjects at baseline, and correlated these data with measures of the clinical features of these subjects. We found that CSF α-syn, t-tau and p-tau levels, but not Aβ1–42, were significantly lower in PD compared with HC, while the diagnostic value of the individual CSF biomarkers for PD diagnosis was limited due to large overlap. The level of α-syn, but not other biomarkers, was significantly lower in PD patients with non-tremor-dominant phenotype compared with tremor-dominant phenotype. In addition, in PD patients the lowest Aβ1–42, or highest t-tau/Aβ1–42 and t-tau/α-syn quintile in PD patients were associated with more severe non-motor dysfunction compared with the highest or lowest quintiles, respectively. In a multivariate regression model, lower α-syn was significantly associated with worse cognitive test performance. APOE ε4 genotype was associated with lower levels of Aβ1–42, but neither with PD diagnosis nor cognition. Our data suggest that the measurement of CSF biomarkers in early-stage PD patients may relate to disease heterogeneity seen in PD. Longitudinal observations in PPMI subjects are needed to define their prognostic performance. PMID:27021906

Reference standard space hippocampus labels according to the European Alzheimer's Disease Consortium-Alzheimer's Disease Neuroimaging Initiative harmonized protocol: Utility in automated volumetry.

PubMed

Wolf, Dominik; Bocchetta, Martina; Preboske, Gregory M; Boccardi, Marina; Grothe, Michel J

2017-08-01

A harmonized protocol (HarP) for manual hippocampal segmentation on magnetic resonance imaging (MRI) has recently been developed by an international European Alzheimer's Disease Consortium-Alzheimer's Disease Neuroimaging Initiative project. We aimed at providing consensual certified HarP hippocampal labels in Montreal Neurological Institute (MNI) standard space to serve as reference in automated image analyses. Manual HarP tracings on the high-resolution MNI152 standard space template of four expert certified HarP tracers were combined to obtain consensual bilateral hippocampus labels. Utility and validity of these reference labels is demonstrated in a simple atlas-based morphometry approach for automated calculation of HarP-compliant hippocampal volumes within SPM software. Individual tracings showed very high agreement among the four expert tracers (pairwise Jaccard indices 0.82-0.87). Automatically calculated hippocampal volumes were highly correlated (r L/R  = 0.89/0.91) with gold standard volumes in the HarP benchmark data set (N = 135 MRIs), with a mean volume difference of 9% (standard deviation 7%). The consensual HarP hippocampus labels in the MNI152 template can serve as a reference standard for automated image analyses involving MNI standard space normalization. Copyright © 2017 the Alzheimer's Association. Published by Elsevier Inc. All rights reserved.

Contacts to general practice and antidepressant treatment initiation after screening for anxiety and depression in patients with heart disease.

PubMed

Larsen, Karen Kjær; Vestergaard, Claus Høstrup; Schougaard, Liv Marit Valen; Larsen, Louise Pape; Jessen, Anne; May, Ole; Hjøllund, Niels Henrik

2016-02-01

Anxiety and depression are found in 20-30% of all persons with heart disease, and depression is known to impact mortality. This paper aimed to describe the effect of systematic screening of this population in terms of use of general practice, psychological therapy and antidepressant treatment. A population-based cohort study was conducted in 2011-2013 comprising 1,658 people with heart disease treated at a Danish regional hospital. Collected data were based on Danish national registers and patient questionnaires. Patients with heart disease and anxiety or depressive symptoms had more general practitioner (GP) contact rates than patients without anxiety or depressive symptoms both before and after the screening. Furthermore, patients with depressive symptoms increased their GP contact rate significantly in the first month after the screening, while this was not the case for patients with anxiety symptoms. Finally, patients with heart disease and anxiety or depressive symptoms more frequently initiated treatment with antidepressants than patients with heart disease without anxiety or depressive symptoms, whereas therapy sessions with a psychologist were rarely used. Heart patients with depressive symptoms may benefit from screening for depression, information about the screening result and a subsequent recommendation to consult their GP in case of signs of depression. -However, the observed effect seems to be modest. The study was supported by an unrestricted grant from the Lundbeck Foundation (grant number: R155-2012-11280). none.

Interactions between Global Health Initiatives and country health systems: the case of a neglected tropical diseases control program in Mali.

PubMed

Cavalli, Anna; Bamba, Sory I; Traore, Mamadou N; Boelaert, Marleen; Coulibaly, Youssouf; Polman, Katja; Pirard, Marjan; Van Dormael, Monique

2010-08-17

Recently, a number of Global Health Initiatives (GHI) have been created to address single disease issues in low-income countries, such as poliomyelitis, trachoma, neonatal tetanus, etc.. Empirical evidence on the effects of such GHIs on local health systems remains scarce. This paper explores positive and negative effects of the Integrated Neglected Tropical Disease (NTD) Control Initiative, consisting in mass preventive chemotherapy for five targeted NTDs, on Mali's health system where it was first implemented in 2007. Campaign processes and interactions with the health system were assessed through participant observation in two rural districts (8 health centres each). Information was complemented by interviews with key informants, website search and literature review. Preliminary results were validated during feedback sessions with Malian authorities from national, regional and district levels. We present positive and negative effects of the NTD campaign on the health system using the WHO framework of analysis based on six interrelated elements: health service delivery, health workforce, health information system, drug procurement system, financing and governance. At point of delivery, campaign-related workload severely interfered with routine care delivery which was cut down or totally interrupted during the campaign, as nurses were absent from their health centre for campaign-related activities. Only 2 of the 16 health centres, characterized by a qualified, stable and motivated workforce, were able to keep routine services running and to use the campaign as an opportunity for quality improvement. Increased workload was compensated by allowances, which significantly improved staff income, but also contributed to divert attention away from core routine activities. While the campaign increased the availability of NTD drugs at country level, parallel systems for drug supply and evaluation requested extra efforts burdening local health systems. The campaign budget

Mastoiditis and facial paralysis as initial manifestations of temporal bone systemic diseases - the significance of the histopathological examination.

PubMed

Maniu, Alma Aurelia; Harabagiu, Oana; Damian, Laura Otilia; Ştefănescu, Eugen HoraŢiu; FănuŢă, Bogdan Marius; Cătană, Andreea; Mogoantă, Carmen Aurelia

2016-01-01

Several systemic diseases, including granulomatous and infectious processes, tumors, bone disorders, collagen-vascular and other autoimmune diseases may involve the middle ear and temporal bone. These diseases are difficult to diagnose when symptoms mimic acute otomastoiditis. The present report describes our experience with three such cases initially misdiagnosed. Their predominating symptoms were otological with mastoiditis, hearing loss, and subsequently facial nerve palsy. The cases were considered an emergency and the patients underwent tympanomastoidectomy, under the suspicion of otitis media with cholesteatoma, in order to remove a possible abscess and to decompress the facial nerve. The common features were the presence of severe granulation tissue filling the mastoid cavity and middle ear during surgery, without cholesteatoma. The definitive diagnoses was made by means of biopsy of the granulation tissue from the middle ear, revealing granulomatosis with polyangiitis (formerly known as Wegener's granulomatosis) in one case, middle ear tuberculosis and diffuse large B-cell lymphoma respectively. After specific associated therapy facial nerve functions improved, and atypical inflammatory states of the ear resolved. As a group, systemic diseases of the middle ear and temporal bone are uncommon, but aggressive lesions. After analyzing these cases and reviewing the literature, we would like to stress upon the importance of microscopic examination of the affected tissue, required for an accurate diagnosis and effective treatment.

Association of FCGR2A rs1801274 polymorphism with susceptibility to autoimmune diseases: A meta-analysis.

PubMed

Zhang, Chang'e; Wang, Wenju; Zhang, Hong'e; Wei, Lulu; Guo, Shuping

2016-06-28

The aim of this meta-analysis was to estimate the association between the FCGR2A rs1801274 polymorphism and the susceptibility to autoimmune diseases more precisely. A meta-analysis was conducted on the association between the FCGR2A gene variants and ADs by allelic contrast, homozygote contrast, the recessive model, and the dominant model. A total of 17 studies with 30 comparisons in different populations and genotype-methods were available for this meta-analysis, including 10 Kawasaki disease (KD), 7 Ulcerative colitis (UC), 6 Crohn's disease (CD), 3 Rheumatoid arthritis (RA), 2 Systemic lupus erythematosus (SLE), 1 Autoimmune thyroid disease (ATD) and 1 diabetes mellitus type 1 (T1D). A significant association between FCGR2A rs1801274 polymorphism were found in KD (OR = 1.409, P < 0.001) and UC (OR = 1.237, P < 0.001). A overall meta-analysis increased risk of AD significant association between FCGR2A rs1801274 gene polymorphism and ADs under allelic (OR = 1.378, P=0.000), homozygous (OR: 1.866, P=0.001), dominant (OR = 1.667, P = 0.000) and recessive (OR = 1.434, P=0.000) in Asian population. Meanwhile, a decreased risk of AD was detected in the allelic (OR= 0.882, P = 0.011), homozygous (OR = 0.777, P = 0.013), dominant (OR = 0.850, P = 0.032) and recessive (OR = 0.840, P = 0.048) in African-American population. This meta-analysis demonstrates that the FCGR2A rs1801274 G-allele confers susceptibility to KD and UC. Data also suggests that the FCGR2A rs1801274 polymorphism may be associated with the susceptibility of multiple ADs in Asian and African-American populations.

Association of FCGR2A rs1801274 polymorphism with susceptibility to autoimmune diseases: A meta-analysis

PubMed Central

Wei, Lulu; Guo, Shuping

2016-01-01

Objectives The aim of this meta-analysis was to estimate the association between the FCGR2A rs1801274 polymorphism and the susceptibility to autoimmune diseases more precisely. Methods A meta-analysis was conducted on the association between the FCGR2A gene variants and ADs by allelic contrast, homozygote contrast, the recessive model, and the dominant model. Results A total of 17 studies with 30 comparisons in different populations and genotype-methods were available for this meta-analysis, including 10 Kawasaki disease (KD), 7 Ulcerative colitis (UC), 6 Crohn's disease (CD), 3 Rheumatoid arthritis (RA), 2 Systemic lupus erythematosus (SLE), 1 Autoimmune thyroid disease (ATD) and 1 diabetes mellitus type 1 (T1D). A significant association between FCGR2A rs1801274 polymorphism were found in KD (OR = 1.409, P < 0.001) and UC (OR = 1.237, P < 0.001). A overall meta-analysis increased risk of AD significant association between FCGR2A rs1801274 gene polymorphism and ADs under allelic (OR = 1.378, P=0.000), homozygous (OR: 1.866, P=0.001), dominant (OR = 1.667, P = 0.000) and recessive (OR = 1.434, P=0.000) in Asian population. Meanwhile, a decreased risk of AD was detected in the allelic (OR= 0.882, P = 0.011), homozygous (OR = 0.777, P = 0.013), dominant (OR = 0.850, P = 0.032) and recessive (OR = 0.840, P = 0.048) in African-American population. Conclusions This meta-analysis demonstrates that the FCGR2A rs1801274 G-allele confers susceptibility to KD and UC. Data also suggests that the FCGR2A rs1801274 polymorphism may be associated with the susceptibility of multiple ADs in Asian and African-American populations. PMID:27270653

Federal Initiative: Tick-Borne Disease Integrated Pest Management White Paper

EPA Pesticide Factsheets

The numbers of human cases of Lyme disease and other tick-borne diseases (TBDs) reported each year to CDC have been increasing steadily in the United States (US), currently totaling tens of thousands of diagnosed human cases annually.

Anticipatory Postural Adjustment During Self-Initiated, Cued, and Compensatory Stepping in Healthy Older Adults and Patients With Parkinson Disease.

PubMed

Schlenstedt, Christian; Mancini, Martina; Horak, Fay; Peterson, Daniel

2017-07-01

To characterize anticipatory postural adjustments (APAs) across a variety of step initiation tasks in people with Parkinson disease (PD) and healthy subjects. Cross-sectional study. Step initiation was analyzed during self-initiated gait, perceptual cued gait, and compensatory forward stepping after platform perturbation. People with PD were assessed on and off levodopa. University research laboratory. People (N=31) with PD (n=19) and healthy aged-matched subjects (n=12). Not applicable. Mediolateral (ML) size of APAs (calculated from center of pressure recordings), step kinematics, and body alignment. With respect to self-initiated gait, the ML size of APAs was significantly larger during the cued condition and significantly smaller during the compensatory condition (P<.001). Healthy subjects and patients with PD did not differ in body alignment during the stance phase prior to stepping. No significant group effect was found for ML size of APAs between healthy subjects and patients with PD. However, the reduction in APA size from cued to compensatory stepping was significantly less pronounced in PD off medication compared with healthy subjects, as indicated by a significant group by condition interaction effect (P<.01). No significant differences were found comparing patients with PD on and off medications. Specific stepping conditions had a significant effect on the preparation and execution of step initiation. Therefore, APA size should be interpreted with respect to the specific stepping condition. Across-task changes in people with PD were less pronounced compared with healthy subjects. Antiparkinsonian medication did not significantly improve step initiation in this mildly affected PD cohort. Copyright © 2016 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Risk Factors in the Initial Presentation of Specific Cardiovascular Disease Syndromes

ClinicalTrials.gov

2013-03-03

Heart Diseases; Cardiovascular Diseases; Acute Myocardial Infarction; Unstable Angina; Chronic Stable Angina; Ischemic Stroke; Cerebrovascular Accident; Subarachnoid Hemorrhage; Transient Ischemic Attack; Abdominal Aortic Aneurysm; Peripheral Arterial Disease; Sudden Coronary Death; Ventricular Arrhythmia; Sudden Death; Cardiac Arrest; Heart Failure

Progression of MDS-UPDRS Scores Over Five Years in De Novo Parkinson Disease from the Parkinson's Progression Markers Initiative Cohort.

PubMed

Holden, Samantha K; Finseth, Taylor; Sillau, Stefan H; Berman, Brian D

2018-01-01

The Movement Disorder Society Unified Parkinson Disease Rating Scale (MDS-UDPRS) is a commonly used tool to measure Parkinson disease (PD) progression. Longitudinal changes in MDS-UPDRS scores in de novo PD have not been established. Determine progression rates of MDS-UPDRS scores in de novo PD. 362 participants from the Parkinson's Progression Markers Initiative, a multicenter longitudinal cohort study of de novo PD, were included. Longitudinal progression of MDS-UPDRS total and subscale scores were modeled using mixed model regression. MDS-UPDRS scores increased in a linear fashion over five years in de novo PD. MDS-UPDRS total score increased an estimated 4.0 points/year, Part I 0.25 points/year, Part II 1.0 points/year, and Part III 2.4 points/year. The expected average progression of MDS-UPDRS scores in de novo PD from this study can assist in clinical monitoring and provide comparative data for detection of disease modification in treatment trials.

Electrocardiographic repolarization-related variables as predictors of coronary heart disease death in the women's health initiative study.

PubMed

Rautaharju, Pentti M; Zhang, Zhu-Ming; Vitolins, Mara; Perez, Marco; Allison, Matthew A; Greenland, Philip; Soliman, Elsayed Z

2014-07-28

We evaluated 25 repolarization-related ECG variables for the risk of coronary heart disease (CHD) death in 52 994 postmenopausal women from the Women's Health Initiative study. Hazard ratios from Cox regression were computed for subgroups of women with and without cardiovascular disease (CVD). During the average follow-up of 16.9 years, 941 CHD deaths occurred. Based on electrophysiological considerations, 2 sets of ECG variables with low correlations were considered as candidates for independent predictors of CHD death: Set 1, Ѳ(Tp|Tref), the spatial angle between T peak (Tp) and normal T reference (Tref) vectors; Ѳ(Tinit|Tterm), the angle between the initial and terminal T vectors; STJ depression in V6 and rate-adjusted QTp interval (QTpa); and Set 2, TaVR and TV1 amplitudes, heart rate, and QRS duration. Strong independent predictors with over 2-fold increased risk for CHD death in women with and without CVD were Ѳ(Tp|Tref) >42° from Set 1 and TaVR amplitude >-100 μV from Set 2. The risk for these CHD death predictors remained significant after multivariable adjustment for demographic/clinical factors. Other significant predictors for CHD death in fully adjusted risk models were Ѳ(Tinit|Tterm) >30°, TV1 >175 μV, and QRS duration >100 ms. Ѳ(Tp|Tref) angle and TaVR amplitude are associated with CHD mortality in postmenopausal women. The use of these measures to identify high-risk women for further diagnostic evaluation or more intense preventive intervention warrants further study. http://www.clinicaltrials.gov. Unique identifier: NCT00000611. © 2014 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

Update on the magnetic resonance imaging core of the Alzheimer's disease neuroimaging initiative.

PubMed

Jack, Clifford R; Bernstein, Matt A; Borowski, Bret J; Gunter, Jeffrey L; Fox, Nick C; Thompson, Paul M; Schuff, Norbert; Krueger, Gunnar; Killiany, Ronald J; Decarli, Charles S; Dale, Anders M; Carmichael, Owen W; Tosun, Duygu; Weiner, Michael W

2010-05-01

Functions of the Alzheimer's Disease Neuroimaging Initiative (ADNI) magnetic resonance imaging (MRI) core fall into three categories: (1) those of the central MRI core laboratory at Mayo Clinic, Rochester, Minnesota, needed to generate high quality MRI data in all subjects at each time point; (2) those of the funded ADNI MRI core imaging analysis groups responsible for analyzing the MRI data; and (3) the joint function of the entire MRI core in designing and problem solving MR image acquisition, pre-processing, and analyses methods. The primary objective of ADNI was and continues to be improving methods for clinical trials in Alzheimer's disease. Our approach to the present ("ADNI-GO") and future ("ADNI-2," if funded) MRI protocol will be to maintain MRI methodological consistency in the previously enrolled "ADNI-1" subjects who are followed up longitudinally in ADNI-GO and ADNI-2. We will modernize and expand the MRI protocol for all newly enrolled ADNI-GO and ADNI-2 subjects. All newly enrolled subjects will be scanned at 3T with a core set of three sequence types: 3D T1-weighted volume, FLAIR, and a long TE gradient echo volumetric acquisition for micro hemorrhage detection. In addition to this core ADNI-GO and ADNI-2 protocol, we will perform vendor-specific pilot sub-studies of arterial spin-labeling perfusion, resting state functional connectivity, and diffusion tensor imaging. One of these sequences will be added to the core protocol on systems from each MRI vendor. These experimental sub-studies are designed to demonstrate the feasibility of acquiring useful data in a multicenter (but single vendor) setting for these three emerging MRI applications. Copyright 2010 The Alzheimer

Factors associated with the initiation of disease-modifying antirheumatic drugs in newly diagnosed rheumatoid arthritis: a retrospective claims database study.

PubMed

Bonafede, Machaon M K; Fox, Kathleen M; Johnson, Barbara H; Watson, Crystal; Gandra, Shravanthi R

2012-02-01

The objectives of this study were to quantify the proportion of US patients with newly diagnosed rheumatoid arthritis (RA) in whom disease-modifying antirheumatic drug (DMARD) therapy was initiated within 12 months following diagnosis, to determine mean time to initiation, to compare the characteristics of initiators versus noninitiators, and to identify factors associated with noninitiation. A retrospective study was conducted using claims from the databases of commercial managed care and Medicare supplemental managed care to identify patients with claims containing codes for RA dated January 1, 2004, through September 30, 2008. The percentage of patients with RA and a prescription for a DMARD within 12 months after the index date (initiators) was evaluated. The characteristics of DMARD initiators and noninitiators during the preindex period were compared, including demographic and clinical characteristics, health care resource utilization, and cost variables. The probability of DMARD initiation was determined using survival analysis. Multivariate analysis was performed to estimate mean time from diagnosis to DMARD initiation based on demographic and clinical variables. Of 26,911 patients with newly diagnosed RA identified in the database searches, 63% had been prescribed a DMARD within 12 months after diagnosis. DMARD initiators were significantly more likely to have had a rheumatologist visit and rheumatoid factor testing and were more likely to have received a corticosteroid and/or an NSAID (all, P < 0.001). DMARD initiators had significantly lower total costs ($10,534 vs $12,725, respectively) and pharmacy drug costs ($2438 vs $2822) over the preindex period compared with noninitiators (both, P < 0.001). Independent factors associated with a greater likelihood of DMARD initiation included a rheumatologist visit, rheumatoid factor testing, NSAID use, and corticosteroid use. Age ≥85 years and the presence of comorbidities were associated with a significantly

Periodontal Disease and Incident Cancer Risk among Postmenopausal Women: Results from the Women's Health Initiative Observational Cohort.

PubMed

Nwizu, Ngozi N; Marshall, James R; Moysich, Kirsten; Genco, Robert J; Hovey, Kathleen M; Mai, Xiaodan; LaMonte, Michael J; Freudenheim, Jo L; Wactawski-Wende, Jean

2017-08-01

Background: Periodontal pathogens have been isolated from precancerous and cancerous lesions and also shown to promote a procarcinogenic microenvironment. Few studies have examined periodontal disease as a risk factor for total cancer, and none have focused on older women. We examined whether periodontal disease is associated with incident cancer among postmenopausal women in the Women's Health Initiative Observational Study. Methods: Our prospective cohort study comprised 65,869 women, ages 54 to 86 years. Periodontal disease information was obtained via self-report questionnaires administered between 1999 and 2003, whereas ascertainment of cancer outcomes occurred through September 2013, with a maximum follow-up period of 15 years. Physician-adjudicated incident total cancers were the main outcomes and site-specific cancers were secondary outcomes. HRs and 95% confidence intervals (CI) were calculated using Cox proportional hazards regression. All analyses were conducted two-sided. Results: During a mean follow-up of 8.32 years, 7,149 cancers were identified. Periodontal disease history was associated with increased total cancer risk (multivariable-adjusted HR, 1.14; 95% CI, 1.08-1.20); findings were similar in analyses limited to 34,097 never-smokers (HR, 1.12; 95% CI, 1.04-1.22). Associations were observed for breast (HR, 1.13; 95% CI, 1.03-1.23), lung (HR, 1.31; 95% CI, 1.14-1.51), esophagus (HR, 3.28; 95% CI, 1.64-6.53), gallbladder (HR, 1.73; 95% CI, 1.01-2.95), and melanoma skin (HR, 1.23; 95% CI, 1.02-1.48) cancers. Stomach cancer was borderline (HR, 1.58; 95% CI, 0.94-2.67). Conclusions: Periodontal disease increases risk of total cancer among older women, irrespective of smoking, and certain anatomic sites appear to be vulnerable. Impact: Our findings support the need for further understanding of the effect of periodontal disease on cancer outcomes. Cancer Epidemiol Biomarkers Prev; 26(8); 1255-65. ©2017 AACR . ©2017 American Association for Cancer

[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.

Foot-and-mouth disease virus receptors: multiple gateways to initiate infection

USDA-ARS?s Scientific Manuscript database

Since its discovery over 100 years ago as the causative agent of foot-and-mouth disease (FMD), research has been directed at understanding the biology of the foot-and-mouth disease virus (FMDV) so as to be able to control this devastating and highly contagious disease of cloven-hoofed livestock. Giv...

Hepatitis C co-infection is associated with an increased risk of incident chronic kidney disease in HIV-infected patients initiating combination antiretroviral therapy.

PubMed

Rossi, Carmine; Raboud, Janet; Walmsley, Sharon; Cooper, Curtis; Antoniou, Tony; Burchell, Ann N; Hull, Mark; Chia, Jason; Hogg, Robert S; Moodie, Erica E M; Klein, Marina B

2017-04-04

Combination antiretroviral therapy (cART) has reduced mortality from AIDS-related illnesses and chronic comorbidities have become prevalent among HIV-infected patients. We examined the association between hepatitis C virus (HCV) co-infection and chronic kidney disease (CKD) among patients initiating modern antiretroviral therapy. Data were obtained from the Canadian HIV Observational Cohort for individuals initiating cART from 2000 to 2012. Incident CKD was defined as two consecutive serum creatinine-based estimated glomerular filtration (eGFR) measurements <60 mL/min/1.73m 2 obtained ≥3 months apart. CKD incidence rates after cART initiation were compared between HCV co-infected and HIV mono-infected patients. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using multivariable Cox regression. We included 2595 HIV-infected patients with eGFR >60 mL/min/1.73m 2 at cART initiation, of which 19% were HCV co-infected. One hundred and fifty patients developed CKD during 10,903 person-years of follow-up (PYFU). The CKD incidence rate was higher among co-infected than HIV mono-infected patients (26.0 per 1000 PYFU vs. 10.7 per 1000 PYFU). After adjusting for demographics, virologic parameters and traditional CKD risk factors, HCV co-infection was associated with a significantly shorter time to incident CKD (HR 1.97; 95% CI: 1.33, 2.90). Additional factors associated with incident CKD were female sex, increasing age after 40 years, lower baseline eGFR below 100 mL/min/1.73m 2 , increasing HIV viral load and cumulative exposure to tenofovir and lopinavir. HCV co-infection was associated with an increased risk of incident CKD among HIV-infected patients initiating cART. HCV-HIV co-infected patients should be monitored for kidney disease and may benefit from available HCV treatments.

Initial combination therapy with ambrisentan and tadalafil in connective tissue disease-associated pulmonary arterial hypertension (CTD-PAH): subgroup analysis from the AMBITION trial

PubMed Central

Coghlan, John Gerry; Galiè, Nazzareno; Barberà, Joan Albert; Frost, Adaani E; Ghofrani, Hossein-Ardeschir; Hoeper, Marius M; Kuwana, Masataka; McLaughlin, Vallerie V; Peacock, Andrew J; Simonneau, Gérald; Vachiéry, Jean-Luc; Blair, Christiana; Gillies, Hunter; Miller, Karen L; Harris, Julia H N; Langley, Jonathan; Rubin, Lewis J

2017-01-01

Background Patients with connective tissue disease-associated pulmonary arterial hypertension (CTD-PAH), in particular systemic sclerosis (SSc), had an attenuated response compared with idiopathic PAH in most trials. Thus, there is uncertainty regarding the benefit of PAH-targeted therapy in some forms of CTD-PAH. Objective To explore the safety and efficacy of initial combination therapy with ambrisentan and tadalafil versus ambrisentan or tadalafil monotherapy in patients with CTD-PAH and SSc-PAH enrolled in the AMBITION trial. Methods This was a post hoc analysis of patients with CTD-PAH and SSc-PAH from AMBITION, an event-driven, double-blind trial in patients with WHO functional class II/III PAH. Treatment-naive patients were randomised 2:1:1 to once-daily initial combination therapy with ambrisentan plus tadalafil or monotherapy with ambrisentan or tadalafil, respectively. The primary endpoint was time to the first clinical failure event (first occurrence of death, hospitalisation for worsening PAH, disease progression or unsatisfactory long-term clinical response). Results In the primary analysis set (N=500), 187 patients had CTD-PAH, of whom 118 had SSc-PAH. Initial combination therapy reduced the risk of clinical failure versus pooled monotherapy in each subgroup: CTD-PAH (HR 0.43 (95% CI 0.24 to 0.77)) and SSc-PAH (0.44 (0.22 to 0.89)). The most common AE was peripheral oedema, which was reported more frequently with initial combination therapy than monotherapy in the two PAH subgroups. The relative frequency of adverse events between those on combination therapy versus monotherapy was similar across subgroups. Conclusions This post hoc subgroup analysis provides evidence that CTD-PAH and SSc-PAH patients benefit from initial ambrisentan and tadalafil combination therapy. Trial registration number NCT01178073, post results. PMID:28039187

Initial combination therapy with ambrisentan and tadalafil in connective tissue disease-associated pulmonary arterial hypertension (CTD-PAH): subgroup analysis from the AMBITION trial.

PubMed

Coghlan, John Gerry; Galiè, Nazzareno; Barberà, Joan Albert; Frost, Adaani E; Ghofrani, Hossein-Ardeschir; Hoeper, Marius M; Kuwana, Masataka; McLaughlin, Vallerie V; Peacock, Andrew J; Simonneau, Gérald; Vachiéry, Jean-Luc; Blair, Christiana; Gillies, Hunter; Miller, Karen L; Harris, Julia H N; Langley, Jonathan; Rubin, Lewis J

2017-07-01

Patients with connective tissue disease-associated pulmonary arterial hypertension (CTD-PAH), in particular systemic sclerosis (SSc), had an attenuated response compared with idiopathic PAH in most trials. Thus, there is uncertainty regarding the benefit of PAH-targeted therapy in some forms of CTD-PAH. To explore the safety and efficacy of initial combination therapy with ambrisentan and tadalafil versus ambrisentan or tadalafil monotherapy in patients with CTD-PAH and SSc-PAH enrolled in the AMBITION trial. This was a post hoc analysis of patients with CTD-PAH and SSc-PAH from AMBITION, an event-driven, double-blind trial in patients with WHO functional class II/III PAH. Treatment-naive patients were randomised 2:1:1 to once-daily initial combination therapy with ambrisentan plus tadalafil or monotherapy with ambrisentan or tadalafil, respectively. The primary endpoint was time to the first clinical failure event (first occurrence of death, hospitalisation for worsening PAH, disease progression or unsatisfactory long-term clinical response). In the primary analysis set (N=500), 187 patients had CTD-PAH, of whom 118 had SSc-PAH. Initial combination therapy reduced the risk of clinical failure versus pooled monotherapy in each subgroup: CTD-PAH (HR 0.43 (95% CI 0.24 to 0.77)) and SSc-PAH (0.44 (0.22 to 0.89)). The most common AE was peripheral oedema, which was reported more frequently with initial combination therapy than monotherapy in the two PAH subgroups. The relative frequency of adverse events between those on combination therapy versus monotherapy was similar across subgroups. This post hoc subgroup analysis provides evidence that CTD-PAH and SSc-PAH patients benefit from initial ambrisentan and tadalafil combination therapy. NCT01178073, post results. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Exploring APOE genotype effects on Alzheimer's disease risk and amyloid β burden in individuals with subjective cognitive decline: The FundacioACE Healthy Brain Initiative (FACEHBI) study baseline results.

PubMed

Moreno-Grau, Sonia; Rodríguez-Gómez, Octavio; Sanabria, Ángela; Pérez-Cordón, Alba; Sánchez-Ruiz, Domingo; Abdelnour, Carla; Valero, Sergi; Hernández, Isabel; Rosende-Roca, Maitée; Mauleón, Ana; Vargas, Liliana; Lafuente, Asunción; Gil, Silvia; Santos-Santos, Miguel Ángel; Alegret, Montserrat; Espinosa, Ana; Ortega, Gemma; Guitart, Marina; Gailhajanet, Anna; de Rojas, Itziar; Sotolongo-Grau, Óscar; Ruiz, Susana; Aguilera, Nuria; Papasey, Judith; Martín, Elvira; Peleja, Esther; Lomeña, Francisco; Campos, Francisco; Vivas, Assumpta; Gómez-Chiari, Marta; Tejero, Miguel Ángel; Giménez, Joan; Serrano-Ríos, Manuel; Orellana, Adelina; Tárraga, Lluís; Ruiz, Agustín; Boada, Mercè

2018-05-01

Subjective cognitive decline (SCD) has been proposed as a potential preclinical stage of Alzheimer's disease (AD). Nevertheless, the genetic and biomarker profiles of SCD individuals remain mostly unexplored. We evaluated apolipoprotein E (APOE) ε4's effect in the risk of presenting SCD, using the Fundacio ACE Healthy Brain Initiative (FACEHBI) SCD cohort and Spanish controls, and performed a meta-analysis addressing the same question. We assessed the relationship between APOE dosage and brain amyloid burden in the FACEHBI SCD and Alzheimer's Disease Neuroimaging Initiative cohorts. Analysis of the FACEHBI cohort and the meta-analysis demonstrated SCD individuals presented higher allelic frequencies of APOE ε4 with respect to controls. APOE dosage explained 9% (FACEHBI cohort) and 11% (FACEHBI and Alzheimer's Disease Neuroimaging Initiative cohorts) of the variance of cerebral amyloid levels. The FACEHBI sample presents APOE ε4 enrichment, suggesting that a pool of AD patients is nested in our sample. Cerebral amyloid levels are partially explained by the APOE allele dosage, suggesting that other genetic or epigenetic factors are involved in this AD endophenotype. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Association between clinically recorded alcohol consumption and initial presentation of 12 cardiovascular diseases: population based cohort study using linked health records.

PubMed

Bell, Steven; Daskalopoulou, Marina; Rapsomaniki, Eleni; George, Julie; Britton, Annie; Bobak, Martin; Casas, Juan P; Dale, Caroline E; Denaxas, Spiros; Shah, Anoop D; Hemingway, Harry

2017-03-22

Objectives  To investigate the association between alcohol consumption and cardiovascular disease at higher resolution by examining the initial lifetime presentation of 12 cardiac, cerebrovascular, abdominal, or peripheral vascular diseases among five categories of consumption. Design  Population based cohort study of linked electronic health records covering primary care, hospital admissions, and mortality in 1997-2010 (median follow-up six years). Setting  CALIBER (ClinicAl research using LInked Bespoke studies and Electronic health Records). Participants  1 937 360 adults (51% women), aged ≥30 who were free from cardiovascular disease at baseline. Main outcome measures  12 common symptomatic manifestations of cardiovascular disease, including chronic stable angina, unstable angina, acute myocardial infarction, unheralded coronary heart disease death, heart failure, sudden coronary death/cardiac arrest, transient ischaemic attack, ischaemic stroke, intracerebral and subarachnoid haemorrhage, peripheral arterial disease, and abdominal aortic aneurysm. Results  114 859 individuals received an incident cardiovascular diagnosis during follow-up. Non-drinking was associated with an increased risk of unstable angina (hazard ratio 1.33, 95% confidence interval 1.21 to 1.45), myocardial infarction (1.32, 1.24 to1.41), unheralded coronary death (1.56, 1.38 to 1.76), heart failure (1.24, 1.11 to 1.38), ischaemic stroke (1.12, 1.01 to 1.24), peripheral arterial disease (1.22, 1.13 to 1.32), and abdominal aortic aneurysm (1.32, 1.17 to 1.49) compared with moderate drinking (consumption within contemporaneous UK weekly/daily guidelines of 21/3 and 14/2 units for men and women, respectively). Heavy drinking (exceeding guidelines) conferred an increased risk of presenting with unheralded coronary death (1.21, 1.08 to 1.35), heart failure (1.22, 1.08 to 1.37), cardiac arrest (1.50, 1.26 to 1.77), transient ischaemic attack (1.11, 1.02 to 1.37), ischaemic stroke (1

Timing of initiation of enzyme replacement therapy after diagnosis of type 1 Gaucher disease: effect on incidence of avascular necrosis

PubMed Central

Mistry, Pramod K; Deegan, Patrick; Vellodi, Ashok; Cole, J Alexander; Yeh, Michael; Weinreb, Neal J

2009-01-01

Data from the International Collaborative Gaucher Group Gaucher Registry were analysed to assess the relationship between enzyme replacement therapy with imiglucerase (ERT) and incidence of avascular necrosis (AVN) in type 1 Gaucher disease (GD1), and to determine whether the time interval between diagnosis and initiation of ERT influences the incidence rate of AVN. All patients with GD1 enrolled in the Gaucher Registry who received ERT and did not report AVN prior to starting therapy (n = 2700) were included. The incidence rate of AVN following initiation of ERT was determined. An incidence rate of AVN of 13·8 per 1000 person-years was observed in patients receiving ERT. Patients who initiated ERT within 2 years of diagnosis had an incidence rate of 8·1 per 1000 person-years; patients who started ERT ≥2 years after diagnosis had an incidence rate of 16·6 per 1000 person-years. The adjusted incidence rate ratio was 0·59 [95% confidence interval (CI) 0·36–0·96, P = 0·0343]. Splenectomy was an independent risk factor for AVN (adjusted incidence rate ratio 2·23, 95% CI 1·61–3·08, P < 0·0001). In conclusion, the risk of AVN was reduced among patients who initiated ERT within 2 years of diagnosis, compared to initiating treatment ≥2 years after diagnosis. A higher risk of AVN was observed among patients who had previously undergone splenectomy. PMID:19732054

The Kidney Disease Outcomes Quality Initiative (K/DOQI) Guideline for Bone Metabolism and Disease in CKD: association with mortality in dialysis patients.

PubMed

Noordzij, Marlies; Korevaar, Johanna C; Boeschoten, Elisabeth W; Dekker, Friedo W; Bos, Willem J; Krediet, Raymond T

2005-11-01

In 2003, the National Kidney Foundation-Kidney Disease Outcomes Quality Initiative (K/DOQI) published a guideline recommending tight control of serum calcium, phosphorus, calcium-phosphorus product (Ca x P), and intact parathyroid hormone levels in patients with chronic kidney disease. Within the context of this guideline, we explored associations of these plasma concentrations with all-cause mortality risk in incident dialysis patients in The Netherlands. In a large, prospective, multicenter, cohort study (Netherlands Cooperative Study on the Adequacy of Dialysis), we included 1,629 patients new on hemodialysis or peritoneal dialysis therapy between 1997 and 2004. Multivariate Cox regression models containing calcium level, phosphorus level, intact parathyroid hormone level, age, comorbidity, primary kidney disease, nutritional status, albumin level, dialysis dose, and hemoglobin level were used to examine mortality risks. Mean age was 60 +/- 15 (SD) years, 61% were men, and 64% were treated with hemodialysis. In adjusted time-dependent survival analysis, all-cause mortality risk increased in hemodialysis patients by 40% (hazard ratio [HR], 1.4; 95% confidence interval [CI], 1.1 to 1.7) and in peritoneal dialysis patients by 60% (HR, 1.6; 95% CI, 1.1 to 2.4) for plasma phosphorus levels greater than the target. In addition, having elevated plasma Ca x P product levels increased mortality risk by 40% (HR, 1.4; 95% CI, 1.1 to 1.8) in hemodialysis patients and 50% in peritoneal dialysis patients (HR, 1.5; 95% CI, 1.0 to 2.2). In both patient groups, no significant effects were observed for plasma levels less than the targets. In time-dependent survival analysis, the presence of plasma phosphorus and Ca x P product concentrations greater than K/DOQI targets increased all-cause mortality risk in hemodialysis and peritoneal dialysis patients.

Rheumatoid Arthritis, Anti-CCP Positivity, and Cardiovascular Disease Risk in the Women’s Health Initiative

PubMed Central

Mackey, Rachel H.; Kuller, Lewis H.; Deane, Kevin D.; Walitt, Brian T.; Chang, Yuefang F.; Holers, V. Michael; Robinson, William H.; Tracy, Russell P.; Hlatky, Mark A.; Eaton, Charles; Liu, Simin; Freiberg, Matthew S.; Talabi, Mehret Birru; Schelbert, Erik B.; Moreland, Larry W.

2015-01-01

Objective This report evaluates incidence of cardiovascular disease (CVD) morbidity and mortality over 10 years among the >160,000 postmenopausal women in the Women’s Health Initiative (WHI) in relation to self-reported RA, disease modifying anti-rheumatic drugs (DMARD) use, anti-CCP+, RF+, CVD risk factors, joint pain, and inflammation (white blood cell (WBC) count and IL-6.) Methods Anti-CCP and RF were measured on a sample (n=9,988) of WHI participants with self-reported RA. RA was classified as self-reported RA plus anti-CCP+ positivity and/or use of DMARDs. Self-reported RA that was both anti-CCP− and DMARD− was classified as “unverified RA.” Results Age-adjusted rates of coronary heart disease (CHD), stroke, CVD, fatal CVD and total mortality were higher for women with RA vs. no RA, with multivariable-adjusted HR(95%CI) of 1.46(1.17, 1.83) for CHD, and 2.55(1.86, 3.51) for fatal CVD. Within RA, anti-CCP+ and RF+ were not significantly associated with higher risk of any outcomes, despite slightly higher risk of fatal CVD and death for anti-CCP+ vs. anti-CCP− RA. Joint pain severity and CVD risk factors were strongly associated with CVD risk, even for women with no RA. CVD incidence was increased for RA vs. no RA at almost all risk factor levels, except low levels of joint pain or inflammation. Within RA, inflammation was more strongly associated with fatal CVD and total mortality than CHD or CVD. Conclusion Among postmenopausal women, RA was associated with 1.5-2.5 higher CVD risk, strongly associated with CV risk factors, joint pain severity, and inflammation, but similar for anti-CCP+ and RF+. Clinical Trial Registration clinicaltrials.gov identifier: NCT00000611 PMID:25988241

Aspiration thrombectomy and intracoronary tirofiban via GuideLiner® catheter for a thrombosed aneurysmal vessel.

PubMed

Fry, James; Naqvi, Ali; Bahia, Amit; Seto, Arnold

2017-03-01

A 52-year-old Asian male with no traditional risk factors for coronary artery disease presented with acute coronary syndrome. Coronary angiography showed complete thrombotic occlusion of the left circumflex with a large thrombus burden in the setting of diffuse aneurysmal enlargement of the coronary arteries consistent with antecedent Kawasaki disease. Manual thrombectomy with adjunctive intracoronary tirofiban was performed utilizing the GuideLiner catheter ® (Vascular Solutions, Inc., MN, USA). Stent implantation was deferred. Follow-up imaging 48 h later showed preserved coronary flow and decreased thrombus burden. The GuideLiner catheter, a monorail guiding device, served a novel role in thrombus aspiration and intracoronary medication delivery.

Clinical trial designs for rare diseases: Studies developed and discussed by the International Rare Cancers Initiative

PubMed Central

Bogaerts, Jan; Sydes, Matthew R.; Keat, Nicola; McConnell, Andrea; Benson, Al; Ho, Alan; Roth, Arnaud; Fortpied, Catherine; Eng, Cathy; Peckitt, Clare; Coens, Corneel; Pettaway, Curtis; Arnold, Dirk; Hall, Emma; Marshall, Ernie; Sclafani, Francesco; Hatcher, Helen; Earl, Helena; Ray-Coquard, Isabelle; Paul, James; Blay, Jean-Yves; Whelan, Jeremy; Panageas, Kathy; Wheatley, Keith; Harrington, Kevin; Licitra, Lisa; Billingham, Lucinda; Hensley, Martee; McCabe, Martin; Patel, Poulam M.; Carvajal, Richard; Wilson, Richard; Glynne-Jones, Rob; McWilliams, Rob; Leyvraz, Serge; Rao, Sheela; Nicholson, Steve; Filiaci, Virginia; Negrouk, Anastassia; Lacombe, Denis; Dupont, Elisabeth; Pauporté, Iris; Welch, John J.; Law, Kate; Trimble, Ted; Seymour, Matthew

2015-01-01

Background The past three decades have seen rapid improvements in the diagnosis and treatment of most cancers and the most important contributor has been research. Progress in rare cancers has been slower, not least because of the challenges of undertaking research. Settings The International Rare Cancers Initiative (IRCI) is a partnership which aims to stimulate and facilitate the development of international clinical trials for patients with rare cancers. It is focused on interventional – usually randomised – clinical trials with the clear goal of improving outcomes for patients. The key challenges are organisational and methodological. A multi-disciplinary workshop to review the methods used in ICRI portfolio trials was held in Amsterdam in September 2013. Other as-yet unrealised methods were also discussed. Results The IRCI trials are each presented to exemplify possible approaches to designing credible trials in rare cancers. Researchers may consider these for use in future trials and understand the choices made for each design. Interpretation Trials can be designed using a wide array of possibilities. There is no ‘one size fits all’ solution. In order to make progress in the rare diseases, decisions to change practice will have to be based on less direct evidence from clinical trials than in more common diseases. PMID:25542058

Meningococcal disease in the Middle East and Africa: Findings and updates from the Global Meningococcal Initiative.

PubMed

Borrow, Ray; Caugant, Dominique A; Ceyhan, Mehmet; Christensen, Hannah; Dinleyici, Ener Cagri; Findlow, Jamie; Glennie, Linda; Von Gottberg, Anne; Kechrid, Amel; Vázquez Moreno, Julio; Razki, Aziza; Smith, Vincent; Taha, Muhamed-Kheir; Tali-Maamar, Hassiba; Zerouali, Khalid

2017-07-01

The Global Meningococcal Initiative (GMI) has recently considered current issues in Middle Eastern and African countries, and produced two recommendations: (i) that vaccination of attendees should be considered for some types of mass-gathering events, as some countries mandate for the Hajj, and (ii) vaccination of people with human immunodeficiency virus should be used routinely, because of increased meningococcal disease (MD) risk. Differences exist between Middle Eastern and African countries regarding case and syndrome definitions, surveillance, and epidemiologic data gaps. Sentinel surveillance provides an overview of trends and prevalence of different capsular groups supporting vaccine selection and planning, whereas cost-effectiveness decisions require comprehensive disease burden data, ideally counting every case. Surveillance data showed importance of serogroup B MD in North Africa and serogroup W expansion in Turkey and South Africa. Success of MenAfriVac ® in the African "meningitis belt" was reviewed; the GMI believes similar benefits may follow development of a low-cost meningococcal pentavalent vaccine, currently in phase 1 clinical trial, by 2022. The importance of carriage and herd protection for controlling invasive MD and the importance of advocacy and awareness campaigns were also highlighted. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Clinical trial designs for rare diseases: studies developed and discussed by the International Rare Cancers Initiative.

PubMed

Bogaerts, Jan; Sydes, Matthew R; Keat, Nicola; McConnell, Andrea; Benson, Al; Ho, Alan; Roth, Arnaud; Fortpied, Catherine; Eng, Cathy; Peckitt, Clare; Coens, Corneel; Pettaway, Curtis; Arnold, Dirk; Hall, Emma; Marshall, Ernie; Sclafani, Francesco; Hatcher, Helen; Earl, Helena; Ray-Coquard, Isabelle; Paul, James; Blay, Jean-Yves; Whelan, Jeremy; Panageas, Kathy; Wheatley, Keith; Harrington, Kevin; Licitra, Lisa; Billingham, Lucinda; Hensley, Martee; McCabe, Martin; Patel, Poulam M; Carvajal, Richard; Wilson, Richard; Glynne-Jones, Rob; McWilliams, Rob; Leyvraz, Serge; Rao, Sheela; Nicholson, Steve; Filiaci, Virginia; Negrouk, Anastassia; Lacombe, Denis; Dupont, Elisabeth; Pauporté, Iris; Welch, John J; Law, Kate; Trimble, Ted; Seymour, Matthew

2015-02-01

The past three decades have seen rapid improvements in the diagnosis and treatment of most cancers and the most important contributor has been research. Progress in rare cancers has been slower, not least because of the challenges of undertaking research. The International Rare Cancers Initiative (IRCI) is a partnership which aims to stimulate and facilitate the development of international clinical trials for patients with rare cancers. It is focused on interventional--usually randomized--clinical trials with the clear goal of improving outcomes for patients. The key challenges are organisational and methodological. A multi-disciplinary workshop to review the methods used in ICRI portfolio trials was held in Amsterdam in September 2013. Other as-yet unrealised methods were also discussed. The IRCI trials are each presented to exemplify possible approaches to designing credible trials in rare cancers. Researchers may consider these for use in future trials and understand the choices made for each design. Trials can be designed using a wide array of possibilities. There is no 'one size fits all' solution. In order to make progress in the rare diseases, decisions to change practice will have to be based on less direct evidence from clinical trials than in more common diseases. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

Comparison of methods for profiling O-glycosylation: Human Proteome Organisation Human Disease Glycomics/Proteome Initiative multi-institutional study of IgA1.

PubMed

Wada, Yoshinao; Dell, Anne; Haslam, Stuart M; Tissot, Bérangère; Canis, Kévin; Azadi, Parastoo; Bäckström, Malin; Costello, Catherine E; Hansson, Gunnar C; Hiki, Yoshiyuki; Ishihara, Mayumi; Ito, Hiromi; Kakehi, Kazuaki; Karlsson, Niclas; Hayes, Catherine E; Kato, Koichi; Kawasaki, Nana; Khoo, Kay-Hooi; Kobayashi, Kunihiko; Kolarich, Daniel; Kondo, Akihiro; Lebrilla, Carlito; Nakano, Miyako; Narimatsu, Hisashi; Novak, Jan; Novotny, Milos V; Ohno, Erina; Packer, Nicolle H; Palaima, Elizabeth; Renfrow, Matthew B; Tajiri, Michiko; Thomsson, Kristina A; Yagi, Hirokazu; Yu, Shin-Yi; Taniguchi, Naoyuki

2010-04-01

The Human Proteome Organisation Human Disease Glycomics/Proteome Initiative recently coordinated a multi-institutional study that evaluated methodologies that are widely used for defining the N-glycan content in glycoproteins. The study convincingly endorsed mass spectrometry as the technique of choice for glycomic profiling in the discovery phase of diagnostic research. The present study reports the extension of the Human Disease Glycomics/Proteome Initiative's activities to an assessment of the methodologies currently used for O-glycan analysis. Three samples of IgA1 isolated from the serum of patients with multiple myeloma were distributed to 15 laboratories worldwide for O-glycomics analysis. A variety of mass spectrometric and chromatographic procedures representative of current methodologies were used. Similar to the previous N-glycan study, the results convincingly confirmed the pre-eminent performance of MS for O-glycan profiling. Two general strategies were found to give the most reliable data, namely direct MS analysis of mixtures of permethylated reduced glycans in the positive ion mode and analysis of native reduced glycans in the negative ion mode using LC-MS approaches. In addition, mass spectrometric methodologies to analyze O-glycopeptides were also successful.

Severely Crusted Cheilitis as an Initial Presentation of Systemic Lupus Erythematosus.

PubMed

Chan, Wai Man Mandy; Pang, Shiu Ming; Ng, See Ket

2017-01-01

Lupus erythematosus (LE) is an autoimmune disease which may initially present solely with lip lesions. Due to a wide spectrum of presentation, these features may initially be misdiagnosed as other oral diseases such as lichen planus, erythema multiforme (EM), and actinic cheilitis, leading to a delay in diagnosis and treatment. We discuss a case of severely crusted cheilitis which was initially diagnosed as EM, with subsequent development of subacute cutaneous LE, and progression to systemic LE. We will discuss the clinical and histological features of lupus cheilitis.

Classification of Chronic Obstructive Pulmonary Disease (COPD) according to the new Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2017: Comparison with GOLD 2011.

PubMed

Marçôa, Raquel; Rodrigues, Daniela Marta; Dias, Margarida; Ladeira, Inês; Vaz, Ana Paula; Lima, Ricardo; Guimarães, Miguel

2018-02-01

Chronic Obstructive Pulmonary Disease (COPD) is a major cause of morbidity and mortality worldwide. The Global Initiative for Chronic Obstructive Lung Disease (GOLD) project has been working to improve awareness, prevention and management of this disease. The aim of this study is to evaluate how COPD patients are reclassified by the 2017 GOLD system (versus GOLD 2011), to calculate the level of agreement between these two classifications in allocation to categories and to compare the performance of each classification to predict future exacerbations. Two-hundred COPD patients (>40 years, post bronchodilator forced expiratory volume in one second/forced vital capacity<0.7) followed in pulmonology consultation were recruited into this prospective multicentric study. Approximately half of the patients classified as GOLD D [2011] changed to GOLD B [2017]. The extent of agreement between GOLD 2011 and GOLD 2017 was moderate (Cohen's Kappa = 0.511; p < 0.001) and the ability to predict exacerbations was similar (69.7% and 67.6%, respectively). GOLD B [2017] exacerbated 17% more than GOLD B [2011] and had a lower percent predicted post bronchodilator forced expiratory volume in one second (FEV1). GOLD B [2017] turned to be the predominant category, more heterogeneous and with a higher risk of exacerbation versus GOLD B [2011]. Physicians should be cautious in assessing the GOLD B [2017] patients. The assessment of patients should always be personalized. More studies are needed to evaluate the impact of the 2017 reclassification in predicting outcomes such as future exacerbations and mortality.

Improved Diagnostic Accuracy of Alzheimer's Disease by Combining Regional Cortical Thickness and Default Mode Network Functional Connectivity: Validated in the Alzheimer's Disease Neuroimaging Initiative Set.

PubMed

Park, Ji Eun; Park, Bumwoo; Kim, Sang Joon; Kim, Ho Sung; Choi, Choong Gon; Jung, Seung Chai; Oh, Joo Young; Lee, Jae-Hong; Roh, Jee Hoon; Shim, Woo Hyun

2017-01-01

To identify potential imaging biomarkers of Alzheimer's disease by combining brain cortical thickness (CThk) and functional connectivity and to validate this model's diagnostic accuracy in a validation set. Data from 98 subjects was retrospectively reviewed, including a study set (n = 63) and a validation set from the Alzheimer's Disease Neuroimaging Initiative (n = 35). From each subject, data for CThk and functional connectivity of the default mode network was extracted from structural T1-weighted and resting-state functional magnetic resonance imaging. Cortical regions with significant differences between patients and healthy controls in the correlation of CThk and functional connectivity were identified in the study set. The diagnostic accuracy of functional connectivity measures combined with CThk in the identified regions was evaluated against that in the medial temporal lobes using the validation set and application of a support vector machine. Group-wise differences in the correlation of CThk and default mode network functional connectivity were identified in the superior temporal ( p < 0.001) and supramarginal gyrus ( p = 0.007) of the left cerebral hemisphere. Default mode network functional connectivity combined with the CThk of those two regions were more accurate than that combined with the CThk of both medial temporal lobes (91.7% vs. 75%). Combining functional information with CThk of the superior temporal and supramarginal gyri in the left cerebral hemisphere improves diagnostic accuracy, making it a potential imaging biomarker for Alzheimer's disease.

Improved Diagnostic Accuracy of Alzheimer's Disease by Combining Regional Cortical Thickness and Default Mode Network Functional Connectivity: Validated in the Alzheimer's Disease Neuroimaging Initiative Set

PubMed Central

Park, Ji Eun; Park, Bumwoo; Kim, Ho Sung; Choi, Choong Gon; Jung, Seung Chai; Oh, Joo Young; Lee, Jae-Hong; Roh, Jee Hoon; Shim, Woo Hyun

2017-01-01

Objective To identify potential imaging biomarkers of Alzheimer's disease by combining brain cortical thickness (CThk) and functional connectivity and to validate this model's diagnostic accuracy in a validation set. Materials and Methods Data from 98 subjects was retrospectively reviewed, including a study set (n = 63) and a validation set from the Alzheimer's Disease Neuroimaging Initiative (n = 35). From each subject, data for CThk and functional connectivity of the default mode network was extracted from structural T1-weighted and resting-state functional magnetic resonance imaging. Cortical regions with significant differences between patients and healthy controls in the correlation of CThk and functional connectivity were identified in the study set. The diagnostic accuracy of functional connectivity measures combined with CThk in the identified regions was evaluated against that in the medial temporal lobes using the validation set and application of a support vector machine. Results Group-wise differences in the correlation of CThk and default mode network functional connectivity were identified in the superior temporal (p < 0.001) and supramarginal gyrus (p = 0.007) of the left cerebral hemisphere. Default mode network functional connectivity combined with the CThk of those two regions were more accurate than that combined with the CThk of both medial temporal lobes (91.7% vs. 75%). Conclusion Combining functional information with CThk of the superior temporal and supramarginal gyri in the left cerebral hemisphere improves diagnostic accuracy, making it a potential imaging biomarker for Alzheimer's disease. PMID:29089831

Myocardial scintigraphy with 201thallium in pediatric cardiology: A review of 52 cases

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

Bjoerkhem, G.E.; Evander, E.; White, T.

1990-01-01

We report our experience of myocardial scintigraphy with 201thallium (201Tl) in 52 children, aged 4 days to 18 years, in which 80 studies were made primarily to demonstrate or exclude impaired myocardial perfusion. For analysis, the patients were divided into the following eight groups: group I, coronary artery malformations (five patients); group II, Kawasaki's syndrome (six patients); group III, arterial switch operation (seven patients); group IV, dilated cardiomyopathy (18 patients); group V, hypertrophic cardiomyopathy (four patients); group VI, myocardial dysfunction after surgery for congenital heart disease (five patients); group VII, pulmonary atresia (three patients); and group VIII, miscellaneous (four patients).more » Myocardial scintigraphy was performed with a planar or tomographic technique at rest or after exercise (four patients). Isotope-uptake defects, indicating impaired myocardial perfusion, were present in 14 patients, including small infants. Defects were seen in all groups except those with hypertrophic cardiomyopathy and pulmonary atresia. The absence of such defects in several of the patients with Kawasaki's syndrome was particularly valuable as it made coronary angiography unnecessary. In the other groups of patients myocardial scintigraphy was a valuable adjunct to other investigations.« less

Women's Initiative for Nonsmoking-VII: evaluation of health service utilization and costs among women smokers with cardiovascular disease.

PubMed

Froelicher, Erika Sivarajan; Sohn, Min; Max, Wendy; Bacchetti, Peter

2004-01-01

The Women's Initiative for Nonsmoking (WINS), a randomized clinical trial of a smoking cessation intervention for women with cardiovascular disease, permitted an assessment of the types and costs of health services women used during the 30 months after their hospitalization with cardiovascular disease. A prospective design nested within WINS was used for this study. A structured telephone interview guide included questions about medical services and 15 categories of prevention services, including cardiac rehabilitation at 6, 12, 24, and 30 months. Costs were estimated from state and national databases. The 277 women studied had a mean age of 60.7 +/- 10 years. They had smoked approximately 40 +/- 11.4 years. More than 50% of the women had one or more risk factors for cardiovascular disease. During the first 6 months after the index hospitalization, 94% had a physician visit, 39% had an emergency-room visit, and 36% had a hospital admission. Prevention services used were home healthcare by nurse or home health aide (26%), a cardiac rehabilitation program, including Multifit and Heart Smart (19%), and physical therapy (14%). Usage decreased over the 30 months. For the women who used any service, the mean total monthly cost per woman was 913 dollars +/- 1204 dollars. This is the first report on health service use by women smokers with cardiovascular disease. Data collection using a telephone interview guide proved feasible for evaluating health service use. The greatest costs resulted from hospital admissions and physician and emergency-room visits. Considering the high prevalence of risk factors in this cohort, secondary prevention services were severely underutilized. By increasing referrals to such services, physicians and nurses might influence women to reduce their risk for subsequent cardiovascular disease.

Matching disease and phenotype ontologies in the ontology alignment evaluation initiative.

PubMed

Harrow, Ian; Jiménez-Ruiz, Ernesto; Splendiani, Andrea; Romacker, Martin; Woollard, Peter; Markel, Scott; Alam-Faruque, Yasmin; Koch, Martin; Malone, James; Waaler, Arild

2017-12-02

The disease and phenotype track was designed to evaluate the relative performance of ontology matching systems that generate mappings between source ontologies. Disease and phenotype ontologies are important for applications such as data mining, data integration and knowledge management to support translational science in drug discovery and understanding the genetics of disease. Eleven systems (out of 21 OAEI participating systems) were able to cope with at least one of the tasks in the Disease and Phenotype track. AML, FCA-Map, LogMap(Bio) and PhenoMF systems produced the top results for ontology matching in comparison to consensus alignments. The results against manually curated mappings proved to be more difficult most likely because these mapping sets comprised mostly subsumption relationships rather than equivalence. Manual assessment of unique equivalence mappings showed that AML, LogMap(Bio) and PhenoMF systems have the highest precision results. Four systems gave the highest performance for matching disease and phenotype ontologies. These systems coped well with the detection of equivalence matches, but struggled to detect semantic similarity. This deserves more attention in the future development of ontology matching systems. The findings of this evaluation show that such systems could help to automate equivalence matching in the workflow of curators, who maintain ontology mapping services in numerous domains such as disease and phenotype.

Polyflex expandable stents in the treatment of esophageal disease: initial experience.

PubMed

Pennathur, Arjun; Chang, Andrew C; McGrath, Kevin M; Steiner, Gregory; Alvelo-Rivera, Miguel; Awais, Omar; Gooding, William E; Christie, Neil A; Gilbert, Sebastien; Landreneau, Rodney J; Luketich, James D

2008-06-01

The new generation of expandable plastic esophageal stents (Polyflex; Boston Scientific, Natick, MA), combine the features of plastic and self-expanding metallic stents. The main objective of this study is to evaluate our initial experience with Polyflex expandable stents in the treatment of esophageal disease from two institutions. A total of 58 Polyflex stents were placed in 38 patients over a two-year period. There were 24 men and 14 women, with a median age of 63 years (range, 25 to 83). The most common indication for placement was an esophageal stricture in 25 patients (66%); other causes included leak in 8 (21%) and tracheoesophageal fistula (TEF) in 5 (13%). We evaluated the hospital course, complications, and outcomes. The median postoperative stay was one day. Complications included migration in 38 stents (63%) (28 patients; 73%), retrosternal chest discomfort in nine, reflux in four, airway obstruction in one, and food impaction in three. Continued leak or a persistent TEF occurred in five patients (38%). Reintervention was required predominantly due to migration of the stent at a mean interval of 46 days (range, 1 to 353). Patients with dysphagia improved significantly with dysphagia scores (1 = no dysphagia; 5 = unable to swallow saliva) improving from 3.44 to 2.15 (p < 0.0001). Polyflex stents were effective in the relief of dysphagia due to strictures. They were less effective in esophageal perforations or leaks. Their primary disadvantage is a high migration rate and further improvements in design are required to decrease this high incidence of migration.

Ultrasound contrast and real-time perfusion in conjunction with supine bicycle stress echocardiography for comprehensive evaluation of surgically corrected congenital heart disease.

PubMed

Kutty, Shelby; Olson, Joan; Danford, Christopher J; Sandene, Erin K; Xie, Feng; Fletcher, Scott E; Erickson, Christopher C; Kugler, John D; Danford, David A; Porter, Thomas R

2012-06-01

We sought to evaluate the efficacy of ultrasound contrast (UC) and low mechanical index real-time perfusion (RTP) in the haemodynamic and anatomic assessment of repaired congenital heart disease (CHD) at rest and during supine bicycle stress echocardiography (BSE). Patients with CHD (n = 51, median age 21.5 years) were prospectively studied. All had compromised image quality, 20 (39%) had arrhythmias, and 10 (20%) had pacemakers. RTP was performed at rest and during BSE using Definity and Contrast Pulse Sequencing, with assessment of Doppler pressure gradients. Diagnoses included tetralogy of Fallot (n = 27), transposition of the great arteries (TGA) atrial switch (n = 10), TGA arterial switch (n = 2), aortic valve disease (n = 4), Fontan (n = 4), and Kawasaki disease (n = 4). UC with RTP improved endocardial border definition, with increased number of left ventricular (LV) and right ventricular (RV) segments visualized at rest (P < 0.0001) and during stress. LV ejection fraction (EF) and RV fractional area change (FAC) were measurable at rest and peak stress, RV FAC correlating closely with same-day magnetic resonance EFs (r = 0.72; P < 0.001). UC enhanced Doppler signals, enabling subpulmonary ventricular systolic pressure measurements at rest and stress. In six patients, marked elevations of subpulmonary ventricular systolic pressure were detected with UC during BSE, and quantifiable ventricular dysfunction. No adverse events occurred, other than transient low back pain in one patient. UC at rest and with supine BSE enables safe and comprehensive assessment of anatomy, haemodynamics, and biventricular functional and perfusion reserve in adolescents and young adults with surgically modified CHD.

The "Choosing Wisely" initiative in infectious diseases.

PubMed

Lehmann, Clara; Berner, Reinhard; Bogner, Johannes R; Cornely, Oliver A; de With, Katja; Herold, Susanne; Kern, Winfried V; Lemmen, Sebastian; Pletz, Mathias W; Ruf, Bernhard; Salzberger, Bernd; Stellbrink, Hans Jürgen; Suttorp, Norbert; Ullmann, Andrew J; Fätkenheuer, Gerd; Jung, Norma

2017-06-01

"Choosing Wisely" is a growing international campaign aiming at practice changes to improve patient health and safety by both, conduct of essential and avoidance of unnecessary diagnostic, preventive and therapeutic procedures. The goal is to create an easily recognizable and distributable list ("Choosing Wisely items") that addresses common over- and underuse in the management of infectious diseases. The German Society of Infectious Diseases (DGI) participates in the campaign "Klug Entscheiden" by the German Society of Internal Medicine. Committee members of the (DGI) listed potential 'Choosing Wisely items'. Topics were subjected to systematic evidence review and top ten items were selected for appropriateness. Five positive and negative recommendations were approved via individual member vote. The final recommendations are: (1) Imperatively start antimicrobial treatment and remove the focus in Staphylococcus aureus bloodstream infection. (2) Critically ill patients with signs of infection need early appropriate antibiotic therapy. (3) Annual influenza vaccination should be given to individuals with age >60 years, patients with specific co-morbidities and to contact persons who may spread influenza to others. (4) All children should receive measles vaccine. (5) Prefer oral formulations of highly bioavailable antimicrobials whenever possible. (6) Avoid prescribing antibiotics for uncomplicated upper respiratory tract infections. (7) Do not treat asymptomatic bacteriuria with antibiotics. (8) Do not treat Candida detected in respiratory or gastrointestinal tract specimens. (9) Do not prolong prophylactic administration of antibiotics in patients after they have left the operating room. (10) Do not treat an elevated C-reactive protein (CRP) or procalcitonin with antibiotics for patients without signs of infection. Physicians will reduce potential harm to patients and increase the value of health care when implementing these recommendations.

The Global Meningococcal Initiative: global epidemiology, the impact of vaccines on meningococcal disease and the importance of herd protection.

PubMed

Borrow, Ray; Alarcón, Pedro; Carlos, Josefina; Caugant, Dominique A; Christensen, Hannah; Debbag, Roberto; De Wals, Philippe; Echániz-Aviles, Gabriela; Findlow, Jamie; Head, Chris; Holt, Daphne; Kamiya, Hajime; Saha, Samir K; Sidorenko, Sergey; Taha, Muhamed-Kheir; Trotter, Caroline; Vázquez Moreno, Julio A; von Gottberg, Anne; Sáfadi, Marco A P

2017-04-01

The 2015 Global Meningococcal Initiative (GMI) meeting discussed the global importance of meningococcal disease (MD) and its continually changing epidemiology. Areas covered: Although recent vaccination programs have been successful in reducing incidence in many countries (e.g. Neisseria meningitidis serogroup [Men]C in Brazil, MenA in the African meningitis belt), new clones have emerged, causing outbreaks (e.g. MenW in South America, MenC in Nigeria and Niger). The importance of herd protection was highlighted, emphasizing the need for high vaccination uptake among those with the highest carriage rates, as was the need for boosters to maintain individual and herd protection following decline of immune response after primary immunization. Expert commentary: The GMI Global Recommendations for Meningococcal Disease were updated to include a recommendation to enable access to whole-genome sequencing as for surveillance, guidance on strain typing to guide use of subcapsular vaccines, and recognition of the importance of advocacy and awareness campaigns.

Predictors of Clinical Progression in HIV-1-Infected Adults Initiating Combination Antiretroviral Therapy with Advanced Disease in the Asia-Pacific Region: Results from the TREAT Asia HIV Observational Database

PubMed Central

Byakwaga, H.; Petoumenos, K.; Ananworanich, J.; Zhang, F.; Boyd, M. A.; Sirisanthana, T.; Li, P. C. K.; Lee, C.; Mean, C. V.; Saphonn, V.; Omar, S. F. S.; Pujari, S.; Phanuphak, P.; Lim, P. L.; Kumarasamy, N.; Chen, Y. M. A.; Merati, T. P.; Sungkanuparph, S.; Ditangco, R.; Oka, S.; Tau, G.; Zhou, J.; Law, M. G.; Emery, S.

2013-01-01

The majority of HIV-infected patients in developing countries commences combination antiretroviral therapy (cART) with advanced disease. We examined predictors of disease progression in patients initiating cART with CD4 count ≤200 cells/mm3 in the TREAT Asia HIV Observational Database. The main outcome measure was progression to either an AIDS-defining illness or death occurring 6 months after initiation of cART. We used survival analysis methods. A total of 1255 patients contributed 2696 person years of follow-up; 73 were diagnosed with AIDS and 9 died. The rate of progression to the combined end point was 3.0 per 100 person years. The factors significantly associated with a higher risk of disease progression were Indian ethnicity, infection through intravenous drug use, lower CD4 count, and hemoglobin ≤130 g/dL at 6 months. In conclusion, measurements of CD4 count and hemoglobin at month 6 may be useful for early identification of disease progression in resource-limited settings. PMID:23422741

Rheumatoid Arthritis and Incidence of Twelve Initial Presentations of Cardiovascular Disease: A Population Record-Linkage Cohort Study in England.

PubMed

Pujades-Rodriguez, Mar; Duyx, Bram; Thomas, Sara L; Stogiannis, Dimitris; Rahman, Anisur; Smeeth, Liam; Hemingway, Harry

2016-01-01

While rheumatoid arthritis is an established risk factor for cardiovascular disease (CVD), our knowledge of how the pattern of risk varies for different cardiovascular phenotypes is incomplete. The association between rheumatoid arthritis and the initial presentation of 12 types of CVDs were examined in a contemporary population of men and women of a wide age range. CALIBER data, which links primary care, hospital and mortality data in England, was analysed. A cohort of people aged ≥18 years and without history of CVD was assembled and included all patients with prospectively recorded rheumatoid arthritis from January 1997, until March 2010, matched with up to ten people without rheumatoid arthritis by age, sex and general practice. The associations between rheumatoid arthritis and the initial presentation of 12 types of CVDs were estimated using multivariable random effects Poisson regression models. The analysis included 12,120 individuals with rheumatoid arthritis and 121,191 comparators. Of these, 2,525 patients with and 18,146 without rheumatoid arthritis developed CVDs during a median of 4.2 years of follow-up. Patients with rheumatoid arthritis had higher rates of myocardial infarction (adjusted incidence ratio [IRR] = 1.43, 95%CI 1.21-1.70), unheralded coronary death (IRR = 1.60, 95%CI 1.18-2.18), heart failure (IRR = 1.61, 95%CI 1.43-1.83), cardiac arrest (HR = 2.26, 95%CI 1.69-3.02) and peripheral arterial disease (HR = 1.36, 95%CI 1.14-1.62); and lower rates of stable angina (HR = 0.83, 95%CI 0.73-0.95). There was no evidence of association with cerebrovascular diseases, abdominal aortic aneurysm or unstable angina, or of interactions with sex or age. The observed associations with some but not all types of CVDs inform both clinical practice and the selection of cardiovascular endpoints for trials and for the development of prognostic models for patients with rheumatoid arthritis.

Earlier defibrotide initiation post-diagnosis of veno-occlusive disease/sinusoidal obstruction syndrome improves Day +100 survival following haematopoietic stem cell transplantation.

PubMed

Richardson, Paul G; Smith, Angela R; Triplett, Brandon M; Kernan, Nancy A; Grupp, Stephan A; Antin, Joseph H; Lehmann, Leslie; Miloslavsky, Maja; Hume, Robin; Hannah, Alison L; Nejadnik, Bijan; Soiffer, Robert J

2017-07-01

Hepatic veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) is a progressive, potentially fatal complication of conditioning for haematopoietic stem cell transplant (HSCT). The VOD/SOS pathophysiological cascade involves endothelial-cell activation and damage, and a prothrombotic-hypofibrinolytic state. Severe VOD/SOS (typically characterized by multi-organ dysfunction) may be associated with >80% mortality. Defibrotide is approved for treating severe hepatic VOD/SOS post-HSCT in the European Union, and for hepatic VOD/SOS with renal or pulmonary dysfunction post-HSCT in the United States. Previously, defibrotide (25 mg/kg/day in 4 divided doses for a recommended ≥21 days) was available through an expanded-access treatment protocol for patients with VOD/SOS. Data from this study were examined post-hoc to determine if the timing of defibrotide initiation post-VOD/SOS diagnosis affected Day +100 survival post-HSCT. Among 573 patients, defibrotide was started on the day of VOD/SOS diagnosis in approximately 30%, and within 7 days in >90%. The relationship between Day +100 survival and treatment initiation before/after specific days post-diagnosis showed superior survival when treatment was initiated closer to VOD/SOS diagnosis with a statistically significant trend over time for better outcomes with earlier treatment initiation (P < 0·001). These results suggest that initiation of defibrotide should not be delayed after diagnosis of VOD/SOS. © 2017 The Authors. British Journal of Haematology published by John Wiley & Sons Ltd.

Diet quality and the risk of cardiovascular disease: the Women's Health Initiative (WHI)123

PubMed Central

Belin, Rashad J; Greenland, Philip; Allison, Matthew; Martin, Lisa; Shikany, James M; Larson, Joseph; Tinker, Lesley; Howard, Barbara V; Lloyd-Jones, Donald

2011-01-01

Background: The association between diet quality and risk of incident cardiovascular disease (CVD) or heart failure (HF) in postmenopausal women is uncertain. Objective: This study aimed to determine whether a conventional index [Alternate Healthy Eating Index (AHEI)] or a novel index [Women's Health Initiative (WHI) Dietary Modification Index (DMI)] of diet quality was associated with the risk of incident CVD or HF in the WHI Observational Study (WHI-OS). Design: The WHI-OS is an observational cohort study of 93,676 women aged 50–79 y of diverse ethnicity and backgrounds followed for an average of 10.0 y for CVD events. The individual components of the AHEI and DMI were determined from the baseline WHI food-frequency questionnaire. Incident CVD was a composite of nonfatal myocardial infarction, coronary heart disease death, stroke, coronary revascularization, and incident HF. The association between AHEI or DMI and incident CVD or incident HF was determined by using Cox models adjusted for traditional CVD and HF risk factors. Results: Women with a DMI in the highest quintile had hazard ratios (HRs) of 0.88 (95% CI: 0.80, 0.95) and 0.91 (95% CI: 0.78, 1.06) for incident CVD and HF, respectively. Women with an AHEI in the highest quintile had HRs of 0.77 (95% CI: 0.70, 0.84) and 0.70 (95% CI: 0.59, 0.82) for incident CVD and HF, respectively. Conclusion: Overall, adherence to current nutrient guidelines (as indexed by the DMI) are associated with lower total CVD risk, and additional dietary factors (as indexed by the AHEI) were associated with a lower risk of CVD and HF. PMID:21613562

The spectrum of rheumatic in-patient diagnoses at a pediatric hospital in Kenya.

PubMed

Migowa, Angela; Colmegna, Inés; Hitchon, Carol; Were, Eugene; Ng'ang'a, Evelyn; Ngwiri, Thomas; Wachira, John; Bernatsky, Sasha; Scuccimarri, Rosie

2017-01-14

Pediatric rheumatic diseases are chronic illnesses that can cause considerable disease burden to children and their families. There is limited epidemiologic data on these diseases in East Africa. The aim of this study was to assess the spectrum of pediatric rheumatic diagnoses in an in-patient setting and determine the accuracy of ICD-10 codes in identifying these conditions. Medical records from Gertrude's Children's Hospital in Kenya were reviewed for patients diagnosed with "diseases of the musculoskeletal system and connective tissue" as per ICD-10 diagnostic codes assigned at discharge between January and December 2011. Cases were classified as "rheumatic" or "non-rheumatic". Accuracy of the assigned ICD-10 code was ascertained. Death records were reviewed. Longitudinal follow-up of "rheumatic" cases was done by chart review up to March 2014. Twenty six patients were classified as having a "rheumatic" condition accounting for 0.32% of patients admitted. Of these, 11 (42.3%) had an acute inflammatory arthropathy, 6 (23.1%) had septic arthritis, 4 (15.4%) had Kawasaki disease, 2 (7.7%) had pyomyositis, and there was one case each of septic bursitis, rheumatic fever, and a non-specific soft tissue disorder. No cases of juvenile idiopathic arthritis (JIA) were identified. One case of systemic lupus erythematosus was documented by death records. The agreement between the treating physician's discharge diagnosis and medical records ICD-10 code assignment was good (Kappa: 0.769). On follow-up, one child had recurrent knee swelling that was suspicious for JIA. Pediatric rheumatic conditions represented 0.32% of admissions at a pediatric hospital in Kenya. Acute inflammatory arthropathies, septic arthritis and Kawasaki disease were the most frequent in-patient rheumatic diagnoses. Chronic pediatric rheumatic diseases were rare amongst this in-patient population. Despite limitations associated with the use of administrative diagnostic codes, they can be a first step in

Disease mongering.

PubMed

Shankar, P R; Subish, P

2007-04-01

Convincing healthy people that they are sick and require medicines can enormously expand the market. Disease mongering can turn ordinary ailments like baldness into medical problems, consider risk factors such as hypertension and osteoporosis as diseases and frame prevalence estimates to increase potential markets. In Asia, conditions like erectile dysfunction, male pattern baldness, attention deficit hyperactivity disorder and irritable bowel syndrome, and the drugs to treat them, are widely promoted. Fairness creams and traditional medicines are also widely used. The cost of disease mongering to the individual and the community is expected to be high. Some authors have argued that medicalisation of illnesses may not be a problem and the real problem may be the lack of medicines. Doctors will play a key role in combating disease mongering. Disentanglement from the pharmaceutical industry and development of a capacity for critical analysis are required. Educating patients and empowering them to make decisions are important. Several initiatives have been undertaken to combat disease mongering. Initiatives at the level of the patient and the physician are especially important. Studies on the extent and knowledge of disease mongering among doctors and medical students, and their economic and social consequences are urgently required.

Medication for Alzheimer’s Disease and Associated Fall Hazard: a Retrospective Cohort Study from the Alzheimer’s Disease Neuro-Imaging Initiative

PubMed Central

Epstein, Noam U.; Guo, Rong; Farlow, Martin R.; Singh, Jaswinder P.; Fisher, Morris

2014-01-01

Background Falls are common in the elderly, especially in those with cognitive impairment. The elderly are often treated with several medications which may have both beneficial and deleterious effects. The use and type of medication in Alzheimer’s patients and association with falls is limited. Objective We examined the association between falls and medication use in the Alzheimer’s Disease Neuro-Imaging Initiative (ADNI). Methods Diagnosis, demographics, medication use, apolipoprotein E4 allele status and functional activity level at baseline were gathered for 810 participants enrolled in ADNI including healthy controls and subjects with mild cognitive impairment or Alzheimer’s. Adverse event fall reports were tabulated. Baseline characteristics were compared between subjects with and without one or more falls. Cox proportional hazards models were conducted to evaluate the association between subject characteristics and hazard of first fall. Results Age (p<0.0001), functional activities questionnaire (p=0.035), Beers list (p=0.0477) and medications for treating cognitive symptoms of Alzheimer’s (p=0.0019) were associated with hazard of fall in the univariate model. In the final multivariate model, after adjusting for covariates, Alzheimer’s medication use (p=0.0005) was associated with hazard of fall. Medication was changed after an adverse fall event by the clinician in 9% of the falls. About 7% of the falls were reported as serious adverse events and 6% were reported to be severe. Conclusion We found a significant association between use of symptomatic medication treating cognitive symptoms in Alzheimer’s disease and hazard of fall after adjusting for age and Beers list medication use. Additional pharmaco-vigilance of the association between falls and Alzheimer’s medication use is warranted. PMID:24357133

Restricted Use of Erythropoiesis-Stimulating Agent is Safe and Associated with Deferred Dialysis Initiation in Stage 5 Chronic Kidney Disease

PubMed Central

Pan, Szu-Yu; Chiang, Wen-Chih; Chen, Ping-Min; Liu, Heng-Hsiu; Chou, Yu-Hsiang; Lai, Tai-Shuan; Lai, Chun-Fu; Chiu, Yen-Ling; Lin, Wan-Yu; Chen, Yung-Ming; Chu, Tzong-Shinn; Lin, Shuei-Liong

2017-01-01

The effect of erythropoiesis-stimulating agent (ESA) on dialysis initiation in advanced chronic kidney disease (CKD) patients is not clear. We retrospectively analyzed the outcome of dialysis initiation in a stage 5 CKD cohort with ESA reimbursement limited to the maximal standardized monthly ESA dose equivalent to epoetin beta 20,000 U by the National Health Insurance program. Totally 423 patients were followed up for a median of 1.37 year. A time-dependent Cox regression model, adjusted for monthly levels of estimated glomerular filtration rate (eGFR) and hemoglobin, was constructed to investigate the association between ESA and outcome. The standardized monthly ESA dose in ESA users was 16,000 ± 3,900 U of epoetin beta. Annual changes of hemoglobin were −0.29 ± 2.19 and −0.99 ± 2.46 g/dL in ESA users and ESA non-users, respectively (P = 0.038). However, annual eGFR decline rates were not different between ESA users and non-users. After adjustment, ESA use was associated with deferred dialysis initiation (hazard ratio 0.63, 95% confidence interval 0.42–0.93, P = 0.021). The protective effect remained when the monthly ESA doses were incorporated. Our data showed that restricted use of ESA was safe and associated with deferred dialysis initiation in stage 5 CKD patients. PMID:28272424