Determinants of initiation and progression of idiopathic pulmonary fibrosis

PubMed Central

Kottmann, Robert Matthew; Hogan, Christopher M.; Phipps, Richard P.; Sime, Patricia J.

2013-01-01

IPF is a devastating disease with few therapeutic options. The precise aetiology of IPF remains elusive. However, our understanding of the pathologic processes involved in the initiation and progression of this disease is improving. Data on the mechanisms underlying IPF have been generated from epidemiologic investigations as well as cellular and molecular studies of human tissues. Although no perfect animal model of human IPF exists, pre-clinical animal studies have helped define pathways which are likely important in human disease. Epithelial injury, fibroblast activation and repetitive cycles of injury and abnormal repair are almost certainly key events. Factors which have been associated with initiation and/or progression of IPF include viral infections, abnormal cytokine, chemokine and growth factor production, oxidant stress, autoimmunity, inhalational of toxicants and gastro-oesophageal reflux disease. Furthermore, recent evidence identifies a role for a variety of genetic and epigenetic abnormalities ranging from mutations in surfactant protein C to abnormalities in telomere length and telomerase activity. The challenge remains to identify additional inciting agents and key dysregulated pathways that lead to disease progression so that we can develop targeted therapies to treat or prevent this serious disease. PMID:19740254

NF-κB activating complex engaged in response to EGFR oncogene inhibition drives tumor cell survival and residual disease in lung cancer

PubMed Central

Blakely, Collin M.; Pazarentzos, Evangelos; Olivas, Victor; Asthana, Saurabh; Yan, Jenny Jiacheng; Tan, Irena; Hrustanovic, Gorjan; Chan, Elton; Lin, Luping; Neel, Dana S.; Newton, William; Bobb, Kathryn; Fouts, Timothy; Meshulam, Jeffrey; Gubens, Matthew A.; Jablons, David M.; Johnson, Jeffrey R.; Bandyopadhyay, Sourav; Krogan, Nevan J.; Bivona, Trever G.

2015-01-01

Summary Although oncogene-targeted therapy often elicits profound initial tumor responses in patients, responses are generally incomplete because some tumor cells survive initial therapy as residual disease that enables eventual acquired resistance. The mechanisms underlying tumor cell adaptation and survival during initial therapy are incompletely understood. Here, through the study of EGFR-mutant lung adenocarcinoma we show that NF-κB signaling is rapidly engaged upon initial EGFR inhibitor treatment to promote tumor cell survival and residual disease. EGFR oncogene inhibition induced an EGFR-TRAF2-RIP1-IKK complex that stimulated an NF-κB-mediated transcriptional survival program. The direct NF-κB inhibitor PBS-1086 suppressed this adaptive survival program and increased the magnitude and duration of initial EGFR inhibitor response in multiple NSCLC models, including a patient-derived xenograft. These findings unveil NF-κB activation as a critical adaptive survival mechanism engaged by EGFR oncogene inhibition and provide rationale for EGFR and NF-κB co-inhibition to eliminate residual disease and enhance patient responses. PMID:25843712

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.

Pigmented extramammary Paget’s disease of the axilla mimicking melanoma: case report and review of the literature

PubMed Central

Hilliard, Nicholaus J; Huang, Conway; Andea, Aleodor

2010-01-01

Pigmented Paget’s disease is a rare variant which is often confused clinically and histologically with melanoma in situ. Herein, we describe a case of pigmented extramammary Paget’s disease involving the axilla of a 79 year old white male thought initially to represent malignant melanoma clinically and histologically. Review of the literature reveals that pigmented variant of Paget’s disease, either mammary or extramammary, could be initially misdiagnosed as melanoma unless this entity is considered in the differential diagnosis and additional confirmatory studies are performed. PMID:19674203

Risk of Unsuccessful Noninvasive Ventilation for Acute Respiratory Failure in Heterogeneous Neuromuscular Diseases: A Retrospective Study.

PubMed

Kataoka, Hiroshi; Nanaura, Hitoki; Kinugawa, Kaoru; Uchihara, Yuto; Ohara, Hiroya; Eura, Nobuyuki; Syobatake, Ryogo; Sawa, Nobuhiro; Takao, Kiriyama; Sugie, Kazuma; Ueno, Satoshi

2017-02-20

If invasive ventilation can be avoided by performing noninvasive mechanical ventilation (NIV) in patients with acute respiratory failure (ARF), the disease can be effectively managed. It is important to clarify the characteristics of patients with neuromuscular diseases in whom initial NIV is likely to be unsuccessful. We studied 27 patients in stable neuromuscular condition who initially received NIV to manage fatal ARF to identify differences in factors immediately before the onset of ARF among patients who receive continuous NIV support, patients who are switched from NIV to invasive ventilation, and patients in whom NIV is discontinued. Endpoints were evaluated 24 and 72 hours after the initiation of NIV. After 24 hours, all but 1 patient with amyotrophic lateral sclerosis (ALS) received continuous NIV support. 72 hours later, 5 patients were switched from NIV to invasive ventilation, and 5 patients continued to receive NIV support. 72 hours after the initiation of NIV, the proportion of patients with a diagnosis of ALS differed significantly among the three groups (P=0.039). NIV may be attempted to manage acute fatal respiratory failure associated with neuromuscular diseases, but clinicians should carefully manage the clinical course in patients with ALS.

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.

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.

A pilot study to improve adherence among MS patients who discontinue treatment against medical advice.

PubMed

Bruce, Jared; Bruce, Amanda; Lynch, Sharon; Strober, Lauren; O'Bryan, Sean; Sobotka, Deborah; Thelen, Joan; Ness, Abigail; Glusman, Morgan; Goggin, Kathy; Bradley-Ewing, Andrea; Catley, Delwyn

2016-04-01

Between 30 and 50% of MS patients may prematurely discontinue disease modifying therapies. Little research has examined how to best talk with patients who have discontinued treatment against medical advice. The aim of this pilot study was to determine whether telephone counseling increases disease modifying therapy (DMT) re-initiation among nonadherent patients with multiple sclerosis (MS). Participants were eligible if they had relapsing-remitting disease, had stopped taking a DMT, and had no plan to re-initiate treatment despite a provider recommendation. Following a baseline assessment, 81 patients were randomly assigned to either five 20 min, weekly sessions of Motivational Interviewing/Cognitive Behavioral Therapy (MI-CBT) or Treatment as Usual (TAU) with brief education. At 10 weeks, patients initially assigned to TAU switched over to MI-CBT. Compared to patients in the TAU group, patients undergoing MI-CBT were significantly more likely to indicate they were re-initiating DMT (41.7 vs. 14.3%). These significant results were replicated among patients crossing over from TAU to MI-CBT. Treatment satisfaction was high, with 97% of participants reporting that they would recommend MI-CBT to other patients with MS. Results of this pilot study provide initial support for the use of MI-CBT among MS patients who have discontinued treatment against medical advice.Clinicaltrials.gov: NCT01925690.

77 FR 5026 - Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Initial Review

Federal Register 2010, 2011, 2012, 2013, 2014

2012-02-01

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Centers for Disease Control and Prevention Disease... Series among Adolescent Females, IP12-004, and Intervention Study to Increase Use of Standing Orders... Series among Adolescent Females, FOA IP12-004; and Intervention Study to Increase Use of Standing Orders...

Abrupt Decline in Kidney Function Before Initiating Hemodialysis and All-Cause Mortality: The Chronic Renal Insufficiency Cohort (CRIC) Study.

PubMed

Hsu, Raymond K; Chai, Boyang; Roy, Jason A; Anderson, Amanda H; Bansal, Nisha; Feldman, Harold I; Go, Alan S; He, Jiang; Horwitz, Edward J; Kusek, John W; Lash, James P; Ojo, Akinlolu; Sondheimer, James H; Townsend, Raymond R; Zhan, Min; Hsu, Chi-Yuan

2016-08-01

It is not clear whether the pattern of kidney function decline in patients with chronic kidney disease (CKD) may relate to outcomes after reaching end-stage renal disease (ESRD). We hypothesize that an abrupt decline in kidney function prior to ESRD predicts early death after initiating maintenance hemodialysis therapy. Prospective cohort study. The Chronic Renal Insufficiency Cohort (CRIC) Study enrolled men and women with mild to moderate CKD. For this study, we studied 661 individuals who developed chronic kidney failure that required hemodialysis therapy initiation. The primary predictor was the presence of an abrupt decline in kidney function prior to ESRD. We incorporated annual estimated glomerular filtration rates (eGFRs) into a mixed-effects model to estimate patient-specific eGFRs at 3 months prior to initiation of hemodialysis therapy. Abrupt decline was defined as having an extrapolated eGFR≥30mL/min/1.73m(2) at that time point. All-cause mortality within 1 year after initiating hemodialysis therapy. Multivariable Cox proportional hazards. Among 661 patients with CKD initiating hemodialysis therapy, 56 (8.5%) had an abrupt predialysis decline in kidney function and 69 died within 1 year after initiating hemodialysis therapy. After adjustment for demographics, cardiovascular disease, diabetes, and cancer, abrupt decline in kidney function was associated with a 3-fold higher risk for death within the first year of ESRD (adjusted HR, 3.09; 95% CI, 1.65-5.76). Relatively small number of outcomes; infrequent (yearly) eGFR determinations; lack of more granular clinical data. Abrupt decline in kidney function prior to ESRD occurred in a significant minority of incident hemodialysis patients and predicted early death in ESRD. Copyright © 2016 National Kidney Foundation, Inc. All rights reserved.

Social Deprivation and Initial Presentation of 12 Cardiovascular Diseases: a CALIBER Study

ClinicalTrials.gov

2013-09-03

Abdominal Aortic Aneurysm; Coronary Heart Disease NOS; Unheralded Corronary 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

Salvage treatment for recurrent oropharyngeal squamous cell carcinoma.

PubMed

Röösli, Christof; Studer, Gabriela; Stoeckli, Sandro J

2010-08-01

This study evaluates the oncological outcome of patients with recurrent oropharyngeal squamous cell carcinoma (OPSCC) after primary radiation therapy +/- chemotherapy, primary surgical therapy, and surgical therapy followed by radiation therapy +/- chemotherapy. A total of 156 patients (36%) of a cohort of 427 treated for OPSCC between 1990 and 2006 developed recurrent disease. Fifty-one patients (12%) qualified for salvage treatment. Study endpoints were 5-year overall survival (OS) and disease-specific survival (DSS). The 5-year OS and DSS rates after salvage treatment were 29% and 40%; after initial primary radiation therapy, 25% and 40%; after initial surgery followed by radiation therapy, 40% and 40%; and after initial surgery alone, 20% and 40%. Patients with an advanced OPSCC have a considerable risk for recurrence. Despite poor ultimate outcome, salvage treatment should be attempted in patients with resectable disease, good performance status, and absence of distant metastases. 2009 Wiley Periodicals, Inc. Head Neck, 2010.

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.

Retrospective comparison of abdominal ultrasonography and radiography in the investigation of feline abdominal disease

PubMed Central

Won, Wylen Wade; Sharma, Ajay; Wu, Wenbo

2015-01-01

Abdominal radiography and ultrasonography are commonly used as part of the initial diagnostic plan for cats with nonspecific signs of abdominal disease. This retrospective study compared the clinical usefulness of abdominal radiography and ultrasonography in 105 feline patients with signs of abdominal disease. The final diagnosis was determined more commonly with ultrasonography (59%) compared to radiography (25.7%). Ultrasonography was also able to provide additional clinically relevant information in 76% of cases, and changed or refined the diagnosis in 47% of cases. Based on these findings, ultrasonography may be sufficient as an initial diagnostic test for the investigation of feline abdominal disease. PMID:26483582

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

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

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...

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.

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

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.

Very long-term sequelae of craniopharyngioma.

PubMed

Wijnen, Mark; van den Heuvel-Eibrink, Marry M; Janssen, Joseph A M J L; Catsman-Berrevoets, Coriene E; Michiels, Erna M C; van Veelen-Vincent, Marie-Lise C; Dallenga, Alof H G; van den Berge, J Herbert; van Rij, Carolien M; van der Lely, Aart-Jan; Neggers, Sebastian J C M M

2017-06-01

Studies investigating long-term health conditions in patients with craniopharyngioma are limited by short follow-up durations and generally do not compare long-term health effects according to initial craniopharyngioma treatment approach. In addition, studies comparing long-term health conditions between patients with childhood- and adult-onset craniopharyngioma report conflicting results. The objective of this study was to analyse a full spectrum of long-term health effects in patients with craniopharyngioma according to initial treatment approach and age group at craniopharyngioma presentation. Cross-sectional study based on retrospective data. We studied a single-centre cohort of 128 patients with craniopharyngioma treated from 1980 onwards (63 patients with childhood-onset disease). Median follow-up since craniopharyngioma presentation was 13 years (interquartile range: 5-23 years). Initial craniopharyngioma treatment approaches included gross total resection ( n  = 25), subtotal resection without radiotherapy ( n  = 44), subtotal resection with radiotherapy ( n  = 25), cyst aspiration without radiotherapy ( n  = 8), and 90 Yttrium brachytherapy ( n  = 21). Pituitary hormone deficiencies (98%), visual disturbances (75%) and obesity (56%) were the most common long-term health conditions observed. Different initial craniopharyngioma treatment approaches resulted in similar long-term health effects. Patients with childhood-onset craniopharyngioma experienced significantly more growth hormone deficiency, diabetes insipidus, panhypopituitarism, morbid obesity, epilepsy and psychiatric conditions compared with patients with adult-onset disease. Recurrence-/progression-free survival was significantly lower after initial craniopharyngioma treatment with cyst aspiration compared with other therapeutic approaches. Survival was similar between patients with childhood- and adult-onset craniopharyngioma. Long-term health conditions were comparable after different initial craniopharyngioma treatment approaches and were generally more frequent in patients with childhood- compared with adult-onset disease. © 2017 European Society of Endocrinology.

Study Provides Insights into Diagnosis, Treatment of Rare Immune Disease: Autoimmmune Lymphoproliferative Syndrome ...

MedlinePlus

... Award Negotiation & Initial Award After Award Foreign Grants Management Getting Your Initial International Award Actions You Can Take as the Project Leader on a Foreign Grant Subawards for Foreign ...

Thinning southern bottomland hardwoods stands: Insect and disease consideratons

Treesearch

T. Evan Nebeker; Theodor D. Leininger; James S. Meadows; Michael D. Warriner

2005-01-01

The effects of thinning on insects and diseases have not been thoroughly examined in southern bottomland hardwood forests. To adress this issue, a study was initiated at sites in Mississippi and Alabama. These study sites allowed us to make observations concerning insect and disease activity 1-5 years following thinning. On all sites there was an unthinned control and...

Simulation of an epidemic model with vector transmission

NASA Astrophysics Data System (ADS)

Dickman, Adriana G.; Dickman, Ronald

2015-03-01

We study a lattice model for vector-mediated transmission of a disease in a population consisting of two species, A and B, which contract the disease from one another. Individuals of species A are sedentary, while those of species B (the vector) diffuse in space. Examples of such diseases are malaria, dengue fever, and Pierce's disease in vineyards. The model exhibits a phase transition between an absorbing (infection free) phase and an active one as parameters such as infection rates and vector density are varied. We study the static and dynamic critical behavior of the model using initial spreading, initial decay, and quasistationary simulations. Simulations are checked against mean-field analysis. Although phase transitions to an absorbing state fall generically in the directed percolation universality class, this appears not to be the case for the present model.

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.

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 is greater than that of the focus. Disease control treatments administered shortly after the initial outbreak within the focus may either prevent an epidemic from occurring or reduce its severity. PMID:25512677

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

Diagnosis of airway obstruction in primary care in the UK: the CADRE (COPD and Asthma Diagnostic/management REassessment) programme 1997-2001.

PubMed

Pearson, Mike; Ayres, Jon G; Sarno, Maria; Massey, Dan; Price, David

2006-01-01

Asthma and COPD require different management strategies, but differentiation in primary care is difficult. This primary care support initiative observed the impact of spirometry and clinical assessment on the diagnosis of airway disease. Of 61,191 patients aged > or =40 years being treated for respiratory conditions within 1003 UK primary care practices, 43,203 underwent a diagnostic review including standardized spirometric assessment. The proportion of patients in whom the diagnosis was changed by the additional information was determined. The relationship of various patient characteristics was compared with the baseline and review diagnoses and with any change in diagnosis. Asthma was initially diagnosed in 43% of patients, COPD in 35%, mixed disease in 9%, and other respiratory condition in 13%. Patients initially diagnosed with asthma, mixed disease, or another condition were more likely to have their diagnosis changed at review (54%, 46%, and 63%, respectively) than those initially diagnosed with COPD (14%). A change from asthma to COPD was associated with male gender, smoking, older age, and reduced lung function, the opposite being associated with a change from COPD to asthma. In this study, a clinical review supplemented by additional information including spirometry highlights apparent mislabeling of significant numbers of patients with chronic obstructive disease in general practice with significant implications for individual treatment and healthcare provision. This study shows that the addition of more clinical information can have a major effect on diagnostic tendency in patients with airway disease. An initial diagnosis of COPD seems less likely to change following review than an asthma diagnosis. While it is likely that greater information leads to a more accurate diagnosis, the differential effect of new information on diagnostic labeling highlights the insecurity of the diagnostic process in primary care in the UK.

[Alzheimer's Therapeutic Research Institute].

PubMed

Shimada, Hiroyuki; Kato, Yuichi; Fujii, Hisako; Mori, Hiroshi

2017-07-01

The Alzheimer's Therapeutic Research Institute (ATRI) was established in 2015 after ATRI director, Paul Aisen, and his fellow experts in therapeutic interventions for Alzheimer's disease (AD) moved from the Alzheimer's Disease Cooperative Study (ADCS) at the University of California to the Keck School of Medicine of the University of Southern California. The National Institute on Aging (NIA) decided to commit $14 million to the ATRI via an Alzheimer's Clinical Trials Consortium (ACTC). The ATRI supports various studies such as the Anti-Amyloid Treatment in Asymptomatic Alzheimer's study ("A4 study"), Alzheimer's Disease Neuroimaging Initiative 3 (ADNI3), Longitudinal Evaluation of Amyloid Risk and Neurodegeneration (LEARN), and The Alzheimer's Disease Neuroimaging Initiative-Depression Project (ADNI-D). The ATRI will share all relevant data and materials with the academic community, corporations, and government organizations. The ATRI is overseen by a Data and Safety Monitoring Board (DSMB), which comprises of leading experts in the field of Alzheimer's research and acts independently. The ATRI is slated to play a central role in clinical dementia research in the US in near future.

The modern pre-levodopa era of Parkinson's disease: insights into motor complications from sub-Saharan Africa.

PubMed

Cilia, Roberto; Akpalu, Albert; Sarfo, Fred Stephen; Cham, Momodou; Amboni, Marianna; Cereda, Emanuele; Fabbri, Margherita; Adjei, Patrick; Akassi, John; Bonetti, Alba; Pezzoli, Gianni

2014-10-01

During the past decade, a number of large drug trials suggested that the initiation of levodopa therapy should be delayed to reduce the risk of motor complications in patients with Parkinson's disease. However, the relative contribution of the cumulative exposure to levodopa and of disease progression to the pathophysiology of motor fluctuations and dyskinesias is still poorly understood. In this 4-year multicentre study, we investigated a large cohort of patients with Parkinson's disease in a sub-Saharan African country (Ghana), where access to medication is limited and the initiation of levodopa therapy often occurs many years after onset. The primary objective was to investigate whether the occurrence of motor complications is primarily related to the duration of levodopa therapy or to disease-related factors. Study design included a cross-sectional case-control analysis of data collected between December 2008 and November 2012, and a prospective study of patients followed-up for at least 6 months after the initiation of levodopa therapy. Ninety-one patients fulfilled criteria for clinical diagnosis of idiopathic Parkinson's disease (58 males, mean age at onset 60.6 ± 11.3 years). Demographic data were compared to those of 2282 consecutive Italian patients recruited during the same period, whereas nested matched subgroups were used to compare clinical variables. Demographic features, frequency and severity of motor and non-motor symptoms were comparable between the two populations, with the only exception of more frequent tremor-dominant presentation in Ghana. At baseline, the proportion of Ghanaian patients with motor fluctuations and dyskinesias was 56% and 14%, respectively. Although levodopa therapy was introduced later in Ghana (mean disease duration 4.2 ± 2.8 versus 2.4 ± 2.1 years, P < 0.001), disease duration at the occurrence of motor fluctuations and dyskinesias was similar in the two populations. In multivariate analysis, disease duration and levodopa daily dose (mg/kg of body weight) were associated with motor complications, while the disease duration at the initiation of levodopa was not. Prospective follow-up for a mean of 2.6 ± 1.3 years of a subgroup of 21 patients who were drug-naïve at baseline [median disease duration 4.5 (interquartile range, 2.3-5) years] revealed that the median time to development of motor fluctuations and dyskinesias after initiation of levodopa therapy was 6 months. We conclude that motor fluctuations and dyskinesias are not associated with the duration of levodopa therapy, but rather with longer disease duration and higher levodopa daily dose. Hence, the practice to withhold levodopa therapy with the objective of delaying the occurrence of motor complications is not justified. © The Author (2014). Published by Oxford University Press on behalf of the Guarantors of Brain.

Cost Comparison of Urate-Lowering Therapies in Patients with Gout and Moderate-to-Severe Chronic Kidney Disease.

PubMed

Mitri, Ghaith; Wittbrodt, Eric T; Turpin, Robin S; Tidwell, Beni A; Schulman, Kathy L

2016-04-01

Patients with chronic kidney disease (CKD) are at increased risk for developing gout and having refractory disease. Gout flare prevention relies heavily on urate-lowering therapies such as allopurinol and febuxostat, but clinical decision making in patients with moderate-to-severe CKD is complicated by significant comorbidity and the scarcity of real-world cost-effectiveness studies. To compare total and disease-specific health care expenditures by line of therapy in allopurinol and febuxostat initiators after diagnosis with gout and moderate-to-severe CKD. A retrospective observational cohort study was conducted to compare mean monthly health care cost (in 2012 U.S. dollars) among gout patients with CKD (stage 3 or 4) who initiated allopurinol or febuxostat. The primary outcome was total mean monthly health care expenditures, and the secondary outcome was disease-specific (gout, diabetes, renal, and cardiovascular disease [CVD]) expenditures. Gout patients (ICD-9-CM 274.xx) aged ≥ 18 years with concurrent CKD (stage 3 or 4) were selected from the MarketScan databases (January 2009-June 2012) upon allopurinol or febuxostat initiation. Patients were followed until disenrollment, discontinuation of the qualifying study agent, or use of the alternate study agent. Patients initiating allopurinol were subsequently propensity score-matched (1:1) to patients initiating febuxostat. Five generalized linear models (GLMs) were developed, each controlling for propensity score, to identify the incremental costs (vs. allopurinol) associated with febuxostat initiation in first-line (without prior allopurinol exposure) and second-line (with prior allopurinol exposure) settings. Propensity score matching yielded 2 cohorts, each with 1,486 patients (64.6% male, mean [SD] age 67.4 [12.8] years). Post-match, 74.6% of patients had stage 3 CKD; 82.9% had CVD; and 42.1% had diabetes. The post-match sample was well balanced on numerous comorbidities and medication exposures with the following exception: 50.0% of febuxostat initiators were treated in the second-line setting; that is, they had baseline exposure to allopurinol, whereas only 4.2% of allopurinol initiators had baseline exposure to febuxostat. Unadjusted mean monthly cost was $1,490 allopurinol and $1,525 febuxostat (P = 0.809). GLM results suggest that first-line febuxostat users incurred significantly (P = 0.009) lower cost than allopurinol users ($1,299 vs. $1,487), whereas second-line febuxostat initiators incurred significantly (P = 0.001) higher cost ($1,751 vs. $1,487). Febuxostat initiators in both settings had significantly (P < 0.001) higher gout-specific cost, due to higher febuxostat acquisition cost. Increased gout-specific cost in the first-line febuxostat cohort was offset by significantly (P < 0.001) lower CVD ($288 vs. $459) and renal-related cost ($86 vs. $216). There were no significant differences in either renal or CVD costs (adjusted) between allopurinol initiators treated almost exclusively in the first-line setting and second-line febuxostat patients. Gout patients with concurrent CKD, initiating treatment with febuxostat in a first-line setting, incurred significantly less total cost than patients initiating allopurinol during the first exposure to each agent. Conversely, patients treated with second-line febuxostat following allopurinol incurred significantly higher total cost than patients initiating allopurinol. There was no significant difference in total cost between the agents across line of therapy. Although study findings suggest the potential for CVD and renal-related savings to offset febuxostat's higher acquisition cost in gout patients with moderate-to-severe CKD, this is the first such retrospective evaluation. Future research is warranted to both demonstrate the durability of study findings and to better elucidate the mechanism by which associated cost offsets occur. No outside funding supported this study. Turpin is an employee of Takeda Pharmaceuticals U.S.A. Mitri and Wittbrodt were employees of Takeda Pharmaceuticals U.S.A. at the time of this study. Tidwell and Schulman are employees of Outcomes Research Solutions, consultants to Takeda Pharmaceuticals U.S.A. All authors contributed to the design of the study and to the writing and review of the manuscript. All authors read and approved the final manuscript. Tidwell and Schulman collected the data, and all authors participated in data interpretation.

[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.

Initial Misdiagnosis of Proximal Pancreatic Adenocarcinoma Is Associated with Delay in Diagnosis and Advanced Stage at Presentation.

PubMed

Swords, Douglas S; Mone, Mary C; Zhang, Chong; Presson, Angela P; Mulvihill, Sean J; Scaife, Courtney L

2015-10-01

Delay in diagnosis of pancreatic ductal adenocarcinoma (PDAC) is associated with decreased survival. The effect of an initial misdiagnosis on delay in diagnosis and stage of PDAC is unknown. This study is a retrospective review (2000-2010) from a University-based cancer center of new diagnoses of proximal PDAC. Of 313 patients, 98 (31.3 %) had an initial misdiagnosis. Misdiagnosed patients were younger, 62.8 ± 12.6 vs. 68.0 ± 10.1 (p < 0.001). The most common initial misdiagnoses were: gallbladder disease, gastroesophageal reflux disease, and peptic ulcer disease. After excluding patients with prior cholecystectomy, 14.2 % were misdiagnosed with gallbladder disease and underwent cholecystectomy before PDAC diagnosis. Misdiagnosed patients had higher rates of abdominal pain (p < 0.001), weight loss (p = 0.04), and acute pancreatitis (p < 0.001) and lower rate of jaundice (p < 0.001). Median time between symptoms to PDAC diagnosis was longer in misdiagnosed: 4.2 months vs. 1.4 (p < 0.001). Median time from contact with medical provider to axial imaging was longer in misdiagnosed (p < 0.001). Rate of stages III-IV disease at diagnosis was higher in misdiagnosed: 61.2 vs. 43.7 % (p = 0.004), with a 1.4 (95 % confidence interval (CI), 1.12-1.74) higher risk of stages III-IV disease at diagnosis; however, there was no difference in median overall survival in misdiagnosed patients (9.6 months in misdiagnosed vs. 10.3 months in correctly diagnosed, p = 0.69). Initial misdiagnosis of patients with proximal PDAC is associated with delay in diagnosis and higher risk of locally advanced or advanced disease at time of PDAC diagnosis.

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...

77 FR 3269 - Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Data...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-01-23

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Centers for Disease Control and Prevention (CDC) Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Data Coordinating Center for Autism and Other Developmental Disabilities Research and Epidemiologic Studies, RFA DD12-001, Initial...

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.

Nutritional impact of inflammatory bowel diseases on children and adolescents☆

PubMed Central

dos Santos, Gilton Marques; Silva, Luciana Rodrigues; Santana, Genoile Oliveira

2014-01-01

OBJECTIVE: To perform a sistematiy review of the literature about the nutritional impact of inflammatory bowel diseases in children and adolescents. DATA SOURCES: A systematic review was performed using PubMed/MEDLINE, LILACS and SciELO databases, with inclusion of articles in Portuguese and in English with original data, that analyzed nutritional aspects of inflammatory bowel diseases in children and adolescents. The initial search used the terms "inflammatory bowel diseases" and "children" or "adolescents" and "nutritional evaluation" or "nutrition deficiency". The selection of studies was initially performed by reading the titles and abstracts. Review studies and those withouth data for pediatric patients were excluded. Subsequently, the full reading of the articles considered relevant was performed. RESULTS: 237 studies were identified, and 12 of them were selected according to the inclusion criteria. None of them was performed in South America. During the analysis of the studies, it was observed that nutritional characteristics of patients with inflammatory bowel disease may be altered; the main reports were related to malnutrition, growth stunting, delayed puberty and vitamin D deficiency. CONCLUSION: There are nutritional consequences of inflammatory bowel diseases in children and adolescents, mainly growth stunting, slower pubertal development, underweight and vitamin deficiencies. Nutritional impairments were more significant in patients with Crohn's disease; overweight and obesity were more common in patients with ulcerative rectocolitis. A detailed nutritional assessment should be performed periodically in children and adolescents with inflammatory bowel disease. PMID:25511006

Barriers to initiating tuberculosis treatment in sub-Saharan Africa: a systematic review focused on children and youth

PubMed Central

Sullivan, Brittney J.; Esmaili, B. Emily; Cunningham, Coleen K.

2017-01-01

ABSTRACT Background: Tuberculosis (TB) is the deadliest infectious disease globally, with 10.4 million people infected and more than 1.8 million deaths in 2015. TB is a preventable, treatable, and curable disease, yet there are numerous barriers to initiating treatment. These barriers to treatment are exacerbated in low-resource settings and may be compounded by factors related to childhood. Objective: Timely initiation of tuberculosis (TB) treatment is critical to reducing disease transmission and improving patient outcomes. The aim of this paper is to describe patient- and system-level barriers to TB treatment initiation specifically for children and youth in sub-Saharan Africa through systematic review of the literature. Design: This review was conducted in October 2015 in accordance with preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines. Six databases were searched to identify studies where primary or secondary objectives were related to barriers to TB treatment initiation and which included children or youth 0–24 years of age. Results: A total of 1490 manuscripts met screening criteria; 152 met criteria for full-text review and 47 for analysis. Patient-level barriers included limited knowledge, attitudes and beliefs regarding TB, and economic burdens. System-level barriers included centralization of services, health system delays, and geographical access to healthcare. Of the 47 studies included, 7 evaluated cost, 19 health-seeking behaviors, and 29 health system infrastructure. Only 4 studies primarily assessed pediatric cohorts yet all 47 studies were inclusive of children. Conclusions: Recognizing and removing barriers to treatment initiation for pediatric TB in sub-Saharan Africa are critical. Both patient- and system-level barriers must be better researched in order to improve patient outcomes. PMID:28598771

AACE/ACE Disease State Clinical Review: Medical Management of Cushing Disease.

PubMed

Hamrahian, Amir H; Yuen, Kevin C J; Hoffman, Andrew R

2014-07-01

To review available medical therapies for patients with Cushing disease and to provide a roadmap for their use in clinical practice. PubMed searches were performed to identify all of the available published data on medical management of Cushing disease. Medical therapy is usually not the first-line treatment for patients with Cushing disease but may be used to improve clinical manifestations of Cushing disease in patients who are not suitable candidates for surgery, following unsuccessful surgery or recurrence, or as a "bridge therapy" in those who have undergone radiotherapy. Medical therapy may also be used in preoperative preparation of patients with severe disease. Current available medical options for patients with Cushing disease include centrally acting agents, steroidogenesis inhibitors, and a glucocorticoid receptor antagonists. At present, there are no head-to-head studies comparing the efficacy, tolerability, and safety of different U.S. Food and Drug Administration (FDA)- and non-FDA-approved drugs in patients with Cushing disease. With the initiation of new studies and the completion of ongoing clinical trials, the number of FDA-approved drugs for medical treatment of Cushing disease is expected to increase. Medical therapy has an important adjunctive role in the management of patients with Cushing disease. The decision to initiate medical treatment depends on many factors, including patient characteristics and preference. Long-term studies are needed to better define the clinical efficacy, safety, and tolerability of medical treatment of Cushing disease, including the role of combination therapies.

Algorithm for optimal dialysis access timing.

PubMed

Heaf, J G

2007-02-01

Acute initiation of dialysis is associated with increased morbidity due to access and uremia complications. It is frequent despite early referral and regular out-patient control. We studied factors associated with end-stage renal disease (ESRD) progression in order to optimize the timing of dialysis access (DA). In a retrospective longitudinal study (Study 1), the biochemical and clinical course of 255 dialysis and 64 predialysis patients was registered to determine factors associated with dialysis-free survival (DFS). On the basis of these results an algorithm was developed to predict timely DA, defined as >6 weeks and <26 weeks before dialysis initiation, with too late placement weighted twice as harmful as too early. The algorithm was validated in a prospective study (Study 2) of 150 dialysis and 28 predialysis patients. Acute dialysis was associated with increased 90-day hospitalization (17.9 vs. 9.0 days) and mortality (14% vs. 6%). P-creatinine and p-urea were poor indicators of DFS. At any level of p-creatinine, DFS was shorter with lower creatinine clearance and vice versa. Patients with systemic renal disease had a significantly shorter DFS than primary renal disease, due to faster GFR loss and earlier dialysis initiation. Short DFS was seen with hypoalbuminemia and cachexia; these patients were recommended early DA. The following algorithm was used to time DA (units: 1iM and ml/min/1.73 m2): P-Creatinine - 50 x GFR + (100 if Systemic Renal Disease) >200. Use of the algorithm was associated with earlier dialysis placement and a fall in acute dialysis requirements from 50% to 23%. The incidence of too early DA was unchanged (7% vs. 9%), and was due to algorithm non-application. The algorithm failed to predict imminent dialysis in 10% of cases, primarily due to acute exacerbation of stable uremia. Dialysis initiation was advanced by approximately one month. A predialysis program based on early dialysis planning and GFR-based DA timing may reduce the requirement for acute dialysis initiation and patient morbidity and mortality, at the cost of slightly earlier dialysis initiation.

Extended Mortality and Chronic Kidney Disease After Septic Acute Kidney Injury.

PubMed

Chua, Horng-Ruey; Wong, Weng-Kin; Ong, Venetia Huiling; Agrawal, Dipika; Vathsala, Anantharaman; Tay, Hui-Ming; Mukhopadhyay, Amartya

2018-01-01

To evaluate 1-year mortality in patients with septic acute kidney injury (AKI) and to determine association between initial AKI recovery patterns ( reversal within 5 days, beyond 5 days but recovery, or nonrecovery) and chronic kidney disease (CKD) progression. Prospective observational study, with retrospective evaluation of initial nonconsenters, of critically ill patients with septic AKI. We studied 207 patients (age, mean [SD]: 64 [16] years, 39% males), of which 56 (27%), 18 (9%), and 9 (4%) died in intensive care unit (ICU), post-ICU in hospital, and posthospitalization, respectively. Infections (including pneumonia) and major adverse cardiac events accounted for 64% and 12% of deaths, respectively. Factors independently associated with 1-year mortality include older age, ischemic heart disease, higher Simplified Acute Physiology Score II, central nervous system or musculoskeletal primary infections, higher daily fluid balance (FB), and frusemide administration during ICU stay (all P < .05). Among 63 patients receiving renal replacement therapy (RRT), hospital mortality was higher with cumulative median FB >8 L versus ≤8 L at RRT initiation (57% vs 24%; P = .009); there was trend for less ICU- and RRT-free days at day 28 in patients with higher FB pre-RRT ( P = NS). Chronic kidney disease progression over 1 year developed in 21%, 30%, and 79% of 105 initial survivors with AKI reversal, recovery, and nonrecovery, respectively ( P < .001). Acute kidney injury nonrecovery during hospitalization independently predicted CKD progression ( P = .001). Patients with septic AKI had 40% 1-year mortality, mainly associated with infections. High FB and frusemide administration were modifiable risk factors. Risk of CKD progression is high especially with initial AKI nonrecovery.

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.

Modeling human mobility responses to the large-scale spreading of infectious diseases.

PubMed

Meloni, Sandro; Perra, Nicola; Arenas, Alex; Gómez, Sergio; Moreno, Yamir; Vespignani, Alessandro

2011-01-01

Current modeling of infectious diseases allows for the study of realistic scenarios that include population heterogeneity, social structures, and mobility processes down to the individual level. The advances in the realism of epidemic description call for the explicit modeling of individual behavioral responses to the presence of disease within modeling frameworks. Here we formulate and analyze a metapopulation model that incorporates several scenarios of self-initiated behavioral changes into the mobility patterns of individuals. We find that prevalence-based travel limitations do not alter the epidemic invasion threshold. Strikingly, we observe in both synthetic and data-driven numerical simulations that when travelers decide to avoid locations with high levels of prevalence, this self-initiated behavioral change may enhance disease spreading. Our results point out that the real-time availability of information on the disease and the ensuing behavioral changes in the population may produce a negative impact on disease containment and mitigation.

Frequency of unrecognized Fabry disease among young European-American and African-American men with first ischemic stroke.

PubMed

Wozniak, Marcella A; Kittner, Steven J; Tuhrim, Stanley; Cole, John W; Stern, Barney; Dobbins, Mark; Grace, Marie E; Nazarenko, Irina; Dobrovolny, Robert; McDade, Eric; Desnick, Robert J

2010-01-01

The cause of initial ischemic stroke in up to 30% of young patients remains unclear. Fabry disease, due to deficient alpha-galactosidase A (alpha-Gal A) activity, is a vascular endothelial glycosphingolipid storage disease typically presenting in childhood. With advancing age, patients develop renal, cardiac, and cerebrovascular disease and die prematurely. A European study suggested an increased prevalence of unrecognized Fabry disease in patients with cryptogenic stroke. We hypothesized that alpha-Gal A deficiency is a rare cause of initial early-onset ischemic stroke in men. The Stroke Prevention in Young Men Study enrolled >550 men (15 to 49 years) with first ischemic stroke in the Baltimore-Washington area in 2004 to 2007. Frozen plasma samples were assayed for alpha-Gal A activity, and DNA from patients with consistently low plasma alpha-Gal A activities were sequenced. The study sample consisted of 558 men (42% African-American; median age 44 years). Stroke was cryptogenic in 154 men (40% African-American). In 10 patients with low plasma alpha-Gal A activities, DNA sequencing identified alterations in the alpha-Gal A gene in 2 patients. The polymorphism, D313Y, which results in low plasma enzyme activity, but near normal levels of cellular activity was seen in one European-American male. The Fabry disease-causing A143T mutation was seen in an African-American male with cryptogenic stroke (0.18% of all strokes: upper 95% CI=0.53%; 0.65% of cryptogenic strokes: upper 95% CI=1.92%). In this biracial population, unrecognized Fabry disease is a rare but treatable cause of initial ischemic stroke in young men.

Development of practical diagnostic methods for monitoring rice bacterial panicle blight disease and evaluation of rice germplasm for resistance

USDA-ARS?s Scientific Manuscript database

A study was initiated to understand Burkholderia glumae, the major causal agent for bacterial panicle blight disease of rice; to develop practical diagnostic methods for monitoring the disease; and to evaluate rice germplasm for resistance. Burkholderia glumae was frequently isolated from infected p...

Development of practical diagnostic methods for monitoring rice bacterial panicle blight disease and evaluation of rice germplasm for resistance

USDA-ARS?s Scientific Manuscript database

A study was initiated to understand Burkholderia glumae (major causal agent for bacterial panicle blight disease of rice) to develop practical diagnostic methods for monitoring the disease; and to evaluate rice germplasm for resistance. B. glumae was frequently isolated from symptomatic panicles on...

Therapy of endocrine disease: outcomes in patients with Cushing's disease undergoing transsphenoidal surgery: systematic review assessing criteria used to define remission and recurrence.

PubMed

Petersenn, Stephan; Beckers, Albert; Ferone, Diego; van der Lely, Aart; Bollerslev, Jens; Boscaro, Marco; Brue, Thierry; Bruzzi, Paolo; Casanueva, Felipe F; Chanson, Philippe; Colao, Annamaria; Reincke, Martin; Stalla, Günter; Tsagarakis, Stelios

2015-06-01

A number of factors can influence the reported outcomes of transsphenoidal surgery (TSS) for Cushing's disease - including different remission and recurrence criteria, for which there is no consensus. Therefore, a comparative analysis of the best treatment options and patient management strategies is difficult. In this review, we investigated the clinical outcomes of initial TSS in patients with Cushing's disease based on definitions of and assessments for remission and recurrence. We systematically searched PubMed and identified 44 studies with clear definitions of remission and recurrence. When data were available, additional analyses by time of remission, tumor size, duration of follow-up, surgical experience, year of study publication and adverse events related to surgery were performed. Data from a total of 6400 patients who received microscopic TSS were extracted and analyzed. A variety of definitions of remission and recurrence of Cushing's disease after initial microscopic TSS was used, giving broad ranges of remission (42.0-96.6%; median, 77.9%) and recurrence (0-47.4%; median, 11.5%). Better remission and recurrence outcomes were achieved for microadenomas vs macroadenomas; however, no correlations were found with other parameters, other than improved safety with longer surgical experience. The variety of methodologies used in clinical evaluation of TSS for Cushing's disease strongly support the call for standardization and optimization of studies to inform clinical practice and maximize patient outcomes. Clinically significant rates of failure of initial TSS highlight the need for effective second-line treatments. © 2015 European Society of Endocrinology.

Poor replication validity of biomedical association studies reported by newspapers

PubMed Central

Smith, Andy; Boraud, Thomas; Gonon, François

2017-01-01

Objective To investigate the replication validity of biomedical association studies covered by newspapers. Methods We used a database of 4723 primary studies included in 306 meta-analysis articles. These studies associated a risk factor with a disease in three biomedical domains, psychiatry, neurology and four somatic diseases. They were classified into a lifestyle category (e.g. smoking) and a non-lifestyle category (e.g. genetic risk). Using the database Dow Jones Factiva, we investigated the newspaper coverage of each study. Their replication validity was assessed using a comparison with their corresponding meta-analyses. Results Among the 5029 articles of our database, 156 primary studies (of which 63 were lifestyle studies) and 5 meta-analysis articles were reported in 1561 newspaper articles. The percentage of covered studies and the number of newspaper articles per study strongly increased with the impact factor of the journal that published each scientific study. Newspapers almost equally covered initial (5/39 12.8%) and subsequent (58/600 9.7%) lifestyle studies. In contrast, initial non-lifestyle studies were covered more often (48/366 13.1%) than subsequent ones (45/3718 1.2%). Newspapers never covered initial studies reporting null findings and rarely reported subsequent null observations. Only 48.7% of the 156 studies reported by newspapers were confirmed by the corresponding meta-analyses. Initial non-lifestyle studies were less often confirmed (16/48) than subsequent ones (29/45) and than lifestyle studies (31/63). Psychiatric studies covered by newspapers were less often confirmed (10/38) than the neurological (26/41) or somatic (40/77) ones. This is correlated to an even larger coverage of initial studies in psychiatry. Whereas 234 newspaper articles covered the 35 initial studies that were later disconfirmed, only four press articles covered a subsequent null finding and mentioned the refutation of an initial claim. Conclusion Journalists preferentially cover initial findings although they are often contradicted by meta-analyses and rarely inform the public when they are disconfirmed. PMID:28222122

Poor replication validity of biomedical association studies reported by newspapers.

PubMed

Dumas-Mallet, Estelle; Smith, Andy; Boraud, Thomas; Gonon, François

2017-01-01

To investigate the replication validity of biomedical association studies covered by newspapers. We used a database of 4723 primary studies included in 306 meta-analysis articles. These studies associated a risk factor with a disease in three biomedical domains, psychiatry, neurology and four somatic diseases. They were classified into a lifestyle category (e.g. smoking) and a non-lifestyle category (e.g. genetic risk). Using the database Dow Jones Factiva, we investigated the newspaper coverage of each study. Their replication validity was assessed using a comparison with their corresponding meta-analyses. Among the 5029 articles of our database, 156 primary studies (of which 63 were lifestyle studies) and 5 meta-analysis articles were reported in 1561 newspaper articles. The percentage of covered studies and the number of newspaper articles per study strongly increased with the impact factor of the journal that published each scientific study. Newspapers almost equally covered initial (5/39 12.8%) and subsequent (58/600 9.7%) lifestyle studies. In contrast, initial non-lifestyle studies were covered more often (48/366 13.1%) than subsequent ones (45/3718 1.2%). Newspapers never covered initial studies reporting null findings and rarely reported subsequent null observations. Only 48.7% of the 156 studies reported by newspapers were confirmed by the corresponding meta-analyses. Initial non-lifestyle studies were less often confirmed (16/48) than subsequent ones (29/45) and than lifestyle studies (31/63). Psychiatric studies covered by newspapers were less often confirmed (10/38) than the neurological (26/41) or somatic (40/77) ones. This is correlated to an even larger coverage of initial studies in psychiatry. Whereas 234 newspaper articles covered the 35 initial studies that were later disconfirmed, only four press articles covered a subsequent null finding and mentioned the refutation of an initial claim. Journalists preferentially cover initial findings although they are often contradicted by meta-analyses and rarely inform the public when they are disconfirmed.

Examining the effects of comorbidities on disease-modifying therapy use in multiple sclerosis

PubMed Central

Zhang, Tingting; Tremlett, Helen; Leung, Stella; Zhu, Feng; Kingwell, Elaine; Fisk, John D.; Bhan, Virender; Campbell, Trudy L.; Stadnyk, Karen; Yu, B. Nancy

2016-01-01

Objective: Comorbidities are common in multiple sclerosis (MS) and adversely affect health outcomes. However, the effect of comorbidity on treatment decisions in MS remains unknown. We aimed to examine the effects of comorbidity on initiation of injectable disease-modifying therapies (DMTs) and on the choice of the initial DMT in MS. Methods: We conducted a retrospective observational analysis using population-based health administrative and linked clinical databases in 3 Canadian provinces. MS cases were defined as any individual with ≥3 diagnostic codes for MS. Cohort entry (index date) was the first recorded demyelinating disease-related claim. The outcomes included choice of initial first-line DMTs and time to initiating a DMT. Logistic and Cox regression models were used to examine the association between comorbidity status and study outcomes, adjusting for sex, age, year of index date, and socioeconomic status. Meta-analysis was used to estimate overall effects across the 3 provinces. Results: We identified 10,698 persons with incident MS, half of whom had ≥1 comorbidities. As the total number of comorbidities increased, the likelihood of initiating a DMT decreased. Comorbid anxiety and ischemic heart disease were associated with reduced initiation of a DMT. However, patients with depression were 13% more likely to initiate a DMT compared to those without depression at the index date (adjusted hazard ratio 1.13; 95% confidence interval 1.00–1.27). Conclusions: Comorbidities are associated with treatment decisions regarding DMTs in MS. A better understanding of the effects of comorbidity on effectiveness and safety of DMTs is needed. PMID:26944268

Characterization of Mineralocorticoid Receptor Antagonist Therapy Initiation in High-Risk Patients With Heart Failure.

PubMed

Cooper, Lauren B; Hammill, Bradley G; Peterson, Eric D; Pitt, Bertram; Maciejewski, Matthew L; Curtis, Lesley H; Hernandez, Adrian F

2017-01-01

Heart failure guidelines recommend routine monitoring of serum potassium, and renal function in patients treated with a mineralocorticoid receptor antagonist (MRA). How these recommendations are implemented in high-risk patients or according to setting of drug initiation is poorly characterized. We conducted a retrospective cohort study of Medicare beneficiaries linked to laboratory data in 10 states with prevalent heart failure as of July 1, 2011, and incident MRA use between May 1 and September 30, 2011. Outcomes included laboratory testing before MRA initiation and in the early (days 1-10) and extended (days 11-90) post-initiation periods, based on setting of drug initiation and the presence of renal insufficiency. Additional outcomes included abnormal laboratory results and adverse events proximate to MRA initiation. Of 10 443 Medicare beneficiaries with heart failure started on an MRA, 19.7% were initiated during a hospitalization. Appropriate follow-up laboratory testing across all time periods occurred in 25.2% of patients with inpatient initiation compared with 2.8% of patients begun as an outpatient. Patients with chronic kidney disease had higher rates of both hyperkalemia and acute kidney failure in the early (1.3% and 2.7%, respectively) and extended (5.6% and 9.8%, respectively) post-initiation periods compared with those without chronic kidney disease. Patients initiated on MRA therapy as an outpatient had extremely poor rates of guideline indicated follow-up laboratory monitoring after drug initiation. In particular, patients with chronic kidney disease are at high risk for adverse events after MRA initiation. Quality improvement initiatives focused on systems to improve appropriate laboratory monitoring are needed. © 2017 American Heart Association, Inc.

Cellular Immune Mechanisms in Malaria.

DTIC Science & Technology

1980-08-31

The initial studies in this area demonstrated the presence of lymphocytotoxins in patients with infectious mononucleosis , rubella, and measles (14...and P.I. Terasaki. 1970. Lymphocytotoxins in Disease I. Infectious mononucleosis , rubella and measles. Lymphocytotoxins in Disease (ed. by P.I

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

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.

Biomarkers intersect with the exposome

PubMed Central

Rappaport, Stephen M.

2016-01-01

The exposome concept promotes use of omic tools for discovering biomarkers of exposure and biomarkers of disease in studies of diseased and healthy populations. A two-stage scheme is presented for profiling omic features in serum to discover molecular biomarkers and then for applying these biomarkers in follow-up studies. The initial component, referred to as an exposome-wide-association study (EWAS), employs metabolomics and proteomics to interrogate the serum exposome and, ultimately, to identify, validate and differentiate biomarkers of exposure and biomarkers of disease. Follow-up studies employ knowledge-driven designs to explore disease causality, prevention, diagnosis, prognosis and treatment. PMID:22672124

[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.

Development of a self-treatment approach for patients with COPD and comorbidities: an ongoing learning process.

PubMed

Effing, Tanja W; Lenferink, Anke; Buckman, Julie; Spicer, Deborah; Cafarella, Paul A; Burt, Morton G; Bassett, Katherine L; van Ommeren, Clara; Anesbury, Sally; van der Valk, Paul D L P M; Frith, Peter A; van der Palen, Job

2014-11-01

Patient-initiated action plans are an important component of COPD self-management (SM) interventions. When integrated into SM interventions, these action plans have proven to be effective in reducing exacerbation severity, hospitalisations, and costs and in improving health status in patients with COPD without severe comorbidities. Because of overlap in symptoms, a self-treatment (ST) approach that focuses solely on traditional symptoms of COPD is inadequate for patients with COPD and comorbidities. The COPE-III SM intervention combines (I) patient-initiated action plans that are tailored to the individual's co-morbid disease(s), and (II) ongoing nurse support. In this paper we provide information regarding the integration of information from two previous COPD SM studies (COPE I and II) in the development of the current COPE-III ST approach. COPE-III ST materials include daily symptom diaries and action plans that take patient's common comorbidities [chronic heart failure (CHF), anxiety, depression, ischaemic heart disease (IHD), and diabetes] into account. The comorbid diary and action plans components were developed in collaboration with multiple disease-experts. Previous SM studies have highlighted some essential topics that need to be considered when developing a SM or ST approach: 'when to initiate ST', 'how to optimize materials and safety', and 'how to achieve behavioural change'. In the COPE-III study, ST is initiated after a significant change in symptoms. This is consistent with the COPE-II approach and was implemented because disease symptoms are often present even when patients are stable. We have tried to ensure patient safety by providing an easily accessible case-manager to patients throughout their involvement in the study. Furthermore, a psychologist has ensured the use of behavioural change techniques throughout the intervention. We should continue to learn from our experiences with SM interventions to further optimize future SM and ST interventions. The use of materials that are suitable for different levels of patient literacy and the training of health care providers are other points of improvement.

Association between GFR Estimated by Multiple Methods at Dialysis Commencement and Patient Survival

PubMed Central

Wong, Muh Geot; Pollock, Carol A.; Cooper, Bruce A.; Branley, Pauline; Collins, John F.; Craig, Jonathan C.; Kesselhut, Joan; Luxton, Grant; Pilmore, Andrew; Harris, David C.

2014-01-01

Summary Background and objectives The Initiating Dialysis Early and Late study showed that planned early or late initiation of dialysis, based on the Cockcroft and Gault estimation of GFR, was associated with identical clinical outcomes. This study examined the association of all-cause mortality with estimated GFR at dialysis commencement, which was determined using multiple formulas. Design, setting, participants, & measurements Initiating Dialysis Early and Late trial participants were stratified into tertiles according to the estimated GFR measured by Cockcroft and Gault, Modification of Diet in Renal Disease, or Chronic Kidney Disease-Epidemiology Collaboration formula at dialysis commencement. Patient survival was determined using multivariable Cox proportional hazards model regression. Results Only Initiating Dialysis Early and Late trial participants who commenced on dialysis were included in this study (n=768). A total of 275 patients died during the study. After adjustment for age, sex, racial origin, body mass index, diabetes, and cardiovascular disease, no significant differences in survival were observed between estimated GFR tertiles determined by Cockcroft and Gault (lowest tertile adjusted hazard ratio, 1.11; 95% confidence interval, 0.82 to 1.49; middle tertile hazard ratio, 1.29; 95% confidence interval, 0.96 to 1.74; highest tertile reference), Modification of Diet in Renal Disease (lowest tertile hazard ratio, 0.88; 95% confidence interval, 0.63 to 1.24; middle tertile hazard ratio, 1.20; 95% confidence interval, 0.90 to 1.61; highest tertile reference), and Chronic Kidney Disease-Epidemiology Collaboration equations (lowest tertile hazard ratio, 0.93; 95% confidence interval, 0.67 to 1.27; middle tertile hazard ratio, 1.15; 95% confidence interval, 0.86 to 1.54; highest tertile reference). Conclusion Estimated GFR at dialysis commencement was not significantly associated with patient survival, regardless of the formula used. However, a clinically important association cannot be excluded, because observed confidence intervals were wide. PMID:24178976

Knowledge and attitude of sexually transmitted diseases among adolescents in Ikeji-Arakeji, Osun State, in South-Western Nigeria.

PubMed

Akokuwebe, M E; Daini, B; Falayi, E O; Oyebade, O

2016-09-01

Globally, sexually transmitted disease (STD) is a public health problem. In Nigeria, adolescents form a substantial proportion (22%) of the population and are particularly prone to STDs because of the influence of peer pressure and urge to experiment sexual activity. The study examined the knowledge and attitude of adolescents towards the prevention of sexually transmitted diseases. The survey study was descriptive cross- sectional and carried out among consenting secondary school students aged 10-24 years completing a self- administered questionnaire on knowledge and attitude in relation to sexually transmitted diseases in Ikeji- Arakeji, Oriade Local government, Osun State, Nigeria. The proportionate sampling technique was used to recruit 341 participants into the study. Data were analyzed using descriptive and inferential statistics. Male-Female distributions were 46.3% and 53.7% respectively. Mean age at first sex (sex initiation) was 16.8 years (approximately 17years) and about 97% of the respondents knew about STDs. The media/ magazine was the major source of information about STDs, accounting for more than half (57%) of the responses on sources of STD information followed closely from that from friends with 31%. Parent's source of information was about 11%. Knowledge of STDs centred mainly on HIV/AIDS with 83% and there was a poor knowledge (78%) of its symptoms. About 40% of all respondents had initiated sex at the time of the study and 46% of the adolescents, as against 54%, thought it was bad to initiate sex before marriage. There was a significant association between perception about initiating sex before marriage and ever having sex using bivariate analysis x(2)=268.4, P<0.001). Also, there was a significant difference between the different groups (sources of information) in influencing sex initiation (F=318.47 and P=0.000). Post-hoc analysis showed that each of the different groups (sources of information) was distinct. Adolescents' knowledge of STDs generally limited to HIV/AIDS and perception about sex significantly influenced the decision to initiate sex. There is, therefore, a serious need to implement sexual education and other sexual and reproductive health interventions early for adolescents in Nigeria.

Verbal and visual memory in patients with early Parkinson's disease: effect of levodopa.

PubMed

Singh, Sumit; Behari, Madhuri

2006-03-01

The effect of initiation of levodopa therapy on the memory functions in patients with Parkinson's disease remains poorly understood. To evaluate the effect of initiation of levodopa therapy on memory, in patients with early Parkinson's disease. Prospective case control study. Seventeen patients with early Parkinson's disease were evaluated for verbal memory using Rey's auditory verbal learning test, and visual memory using the Benton's visual retention test and Form sequence learning test. UPDRS scores, Hoehn and Yahr's Staging and Schwab and England scores of Activities of daily living. Hamilton's depression rating scale and MMSE were also evaluated. Six controls were also evaluated according to similar study protocol. Levodopa was then prescribed to the cases. Same tests were repeated on all the subjects after 12 weeks. The mean age of the patients was 59.8 (+ 12.9 yrs); mean disease duration of 3.26 (+ 2.06 yrs). The mean UPDRS scores of patients were 36.52 (+ 15.84). Controls were of a similar age and sex distribution. A statistically significant improvement in the scores on the UPDRS, Hamilton's depression scale, Schwab and England scale, and a statistically significant deterioration in the scores of visual memory was observed in patients with PD after starting levodopa, as compared to their baseline scores. There was no correlation between degree of deterioration and the dose of levodopa. Initiation of levodopa therapy in patients with early and stable Parkinson's disease is associated with deterioration in visual memory functions, with relative preservation of the verbal memory.

Pathogenesis of achalasia cardia.

PubMed

Ghoshal, Uday C; Daschakraborty, Sunil B; Singh, Renu

2012-06-28

Achalasia cardia is one of the common causes of motor dysphagia. Though the disease was first described more than 300 years ago, exact pathogenesis of this condition still remains enigmatic. Pathophysiologically, achalasia cardia is caused by loss of inhibitory ganglion in the myenteric plexus of the esophagus. In the initial stage, degeneration of inhibitory nerves in the esophagus results in unopposed action of excitatory neurotransmitters such as acetylcholine, resulting in high amplitude non-peristaltic contractions (vigorous achalasia); progressive loss of cholinergic neurons over time results in dilation and low amplitude simultaneous contractions in the esophageal body (classic achalasia). Since the initial description, several studies have attempted to explore initiating agents that may cause the disease, such as viral infection, other environmental factors, autoimmunity, and genetic factors. Though Chagas disease, which mimics achalasia, is caused by an infective agent, available evidence suggests that infection may not be an independent cause of primary achalasia. A genetic basis for achalasia is supported by reports showing occurrence of disease in monozygotic twins, siblings and other first-degree relatives and occurrence in association with other genetic diseases such as Down's syndrome and Parkinson's disease. Polymorphisms in genes encoding for nitric oxide synthase, receptors for vasoactive intestinal peptide, interleukin 23 and the ALADIN gene have been reported. However, studies on larger numbers of patients and controls from different ethnic groups are needed before definite conclusions can be obtained. Currently, the disease is believed to be multi-factorial, with autoimmune mechanisms triggered by infection in a genetically predisposed individual leading to degeneration of inhibitory ganglia in the wall of the esophagus.

Pathogenesis of achalasia cardia

PubMed Central

Ghoshal, Uday C; Daschakraborty, Sunil B; Singh, Renu

2012-01-01

Achalasia cardia is one of the common causes of motor dysphagia. Though the disease was first described more than 300 years ago, exact pathogenesis of this condition still remains enigmatic. Pathophysiologically, achalasia cardia is caused by loss of inhibitory ganglion in the myenteric plexus of the esophagus. In the initial stage, degeneration of inhibitory nerves in the esophagus results in unopposed action of excitatory neurotransmitters such as acetylcholine, resulting in high amplitude non-peristaltic contractions (vigorous achalasia); progressive loss of cholinergic neurons over time results in dilation and low amplitude simultaneous contractions in the esophageal body (classic achalasia). Since the initial description, several studies have attempted to explore initiating agents that may cause the disease, such as viral infection, other environmental factors, autoimmunity, and genetic factors. Though Chagas disease, which mimics achalasia, is caused by an infective agent, available evidence suggests that infection may not be an independent cause of primary achalasia. A genetic basis for achalasia is supported by reports showing occurrence of disease in monozygotic twins, siblings and other first-degree relatives and occurrence in association with other genetic diseases such as Down’s syndrome and Parkinson’s disease. Polymorphisms in genes encoding for nitric oxide synthase, receptors for vasoactive intestinal peptide, interleukin 23 and the ALADIN gene have been reported. However, studies on larger numbers of patients and controls from different ethnic groups are needed before definite conclusions can be obtained. Currently, the disease is believed to be multi-factorial, with autoimmune mechanisms triggered by infection in a genetically predisposed individual leading to degeneration of inhibitory ganglia in the wall of the esophagus. PMID:22791940

Antiretroviral therapy CNS penetration and HIV-1-associated CNS disease.

PubMed

Garvey, L; Winston, A; Walsh, J; Post, F; Porter, K; Gazzard, B; Fisher, M; Leen, C; Pillay, D; Hill, T; Johnson, M; Gilson, R; Anderson, J; Easterbrook, P; Bansi, L; Orkin, C; Ainsworth, J; Palfreeman, A; Gompels, M; Phillips, A N; Sabin, C A

2011-02-22

The impact of different antiretroviral agents on the risk of developing or surviving CNS disease remains unknown. The aim of this study was to investigate whether using antiretroviral regimens with higher CNS penetration effectiveness (CPE) scores was associated with reduced incidence of CNS disease and improved survival in the UK Collaborative HIV Cohort (CHIC) Study. Adults without previous CNS disease, who commenced combination antiretroviral therapy (cART) between 1996 and 2008, were included (n = 22,356). Initial and most recent cART CPE scores were calculated. CNS diseases were HIV encephalopathy (HIVe), progressive multifocal leukoencephalopathy (PML), cerebral toxoplasmosis (TOXO), and cryptococcal meningitis (CRYPTO). Incidence rates and overall survival were stratified by CPE score. A multivariable Poisson regression model was used to identify independent associations. The median (interquartile range) CPE score for initial cART regimen increased from 7 (5-8) in 1996-1997 to 9 (8-10) in 2000-2001 and subsequently declined to 6 (7-8) in 2006-2008. Differences in gender, HIV acquisition risk group, and ethnicity existed between CPE score strata. A total of 251 subjects were diagnosed with a CNS disease (HIVe 80; TOXO 59; CRYPTO 56; PML 54). CNS diseases occurred more frequently in subjects prescribed regimens with CPE scores ≤ 4, and less frequently in those with scores ≥ 10; however, these differences were nonsignificant. Initial and most recent cART CPE scores ≤ 4 were independently associated with increased risk of death. Clinical status at time of commencing cART influences antiretroviral selection and CPE score. This information should be considered when utilizing CPE scores for retrospective analyses.

High-sensitive factor I and C-reactive protein based biomarkers for coronary artery disease.

PubMed

Zhao, Qing; Du, Jian-Shi; Han, Dong-Mei; Ma, Ying

2014-01-01

An analysis of high-sensitive factor I and C-reactive proteins as biomarkers for coronary artery disease has been performed from 19 anticipated cohort studies that included 21,567 participants having no information about coronary artery disease. Besides, the clinical implications of statin therapy initiated due to assessment of factor I and C-reactive proteins have also been modeled during studies. The measure of risk discrimination (C-index) was increased (by 0.0101) as per the prognostic model for coronary artery disease with respect to sex, smoking status, age, blood pressure, total cholesterol level along with diabetic history characteristic parameters. The C-index was further raised by 0.0045 and 0.0053 when factor I and C-reactive proteins based information were added, respectively which finally predicted 10-year risk categories as: high (> 20%), medium (10% to < 20%), and low (< 10%) risks. We found 2,254 persons (among 15,000 adults (age ≥ 45 years)) would initially be classified as being at medium risk for coronary artery disease when only conventional risk factors were used as calculated risk. Besides, persons with a predicted risk of more than 20% as well as for persons suffering from other risk factors (i.e. diabetes), statin therapy was initiated (irrespective of their decade old predicted risk). We conclude that under current treatment guidelines assessment of factor I and C-reactive proteins levels (as biomarker) in people at medium risk for coronary artery disease could prevent one additional coronary artery disease risk over a period a decade for every 390-500 people screened.

Use of Abacavir and Risk of Cardiovascular Disease Among HIV-Infected Individuals.

PubMed

Marcus, Julia L; Neugebauer, Romain S; Leyden, Wendy A; Chao, Chun R; Xu, Lanfang; Quesenberry, Charles P; Klein, Daniel B; Towner, William J; Horberg, Michael A; Silverberg, Michael J

2016-04-01

Evidence is conflicting about the association of abacavir use and cardiovascular disease (CVD) among HIV-infected individuals. Previous studies may have been biased by the preferential initiation or continuation of abacavir in patients with renal dysfunction. We conducted a cohort study in Kaiser Permanente California during 1998-2011, following HIV-infected adults initiating antiretroviral therapy until the earliest of CVD (ie, coronary heart disease or ischemic stroke), health plan disenrollment, death, or end of study. We used inverse-probability weighting to fit marginal structural models to estimate hazard ratios (HRs) for CVD comparing regimens with and without abacavir. Propensity score models included demographics, HIV-specific factors, and CVD risk factors, including alcohol/drug use, smoking, overweight/obesity, diabetes, lipid-lowering and hypertension therapy, and renal dysfunction (ie, estimated glomerular filtration rate <60 mL·min·1.73 m). Among 8154 subjects, 178 had ≥1 CVD event, with 24/704 (3.4%) in the abacavir group and 154/7450 (2.1%) in the group initiating regimens without abacavir. Abacavir users had more renal dysfunction at antiretroviral therapy initiation (7.0% vs. 3.3%, P < 0.001). Compared with patients initiating regimens without abacavir, abacavir users had a 2.2-fold higher risk of CVD in intention-to-treat analysis [HR 2.2, 95% confidence interval (CI): 1.4 to 3.5], a 2.7-fold higher risk when remaining on their initial regimens for ≥1 year (HR 2.7, 95% CI: 1.5 to 5.0), and a 2.1-fold higher risk in per-protocol analysis (HR 2.1, 95% CI: 0.9 to 5.0). Abacavir was associated with an over 2-fold increased risk of CVD, which was not explained by renal dysfunction or other CVD risk factors.

Genital HSV Shedding among Kenyan Women Initiating Antiretroviral Therapy

PubMed Central

Manguro, Griffins O.; Masese, Linnet N.; Deya, Ruth W.; Magaret, Amalia; Wald, Anna; McClelland, R. Scott; Graham, Susan M.

2016-01-01

Objectives Genital ulcer disease (GUD) prevalence increases in the first month of antiretroviral treatment (ART), followed by a return to baseline prevalence by month 3. Since most GUD is caused by herpes simplex virus type 2 (HSV-2), we hypothesized that genital HSV detection would follow a similar pattern after treatment initiation. Methods We conducted a prospective cohort study of 122 HSV-2 and HIV-1 co-infected women with advanced HIV disease who initiated ART and were followed closely with collection of genital swab specimens for the first three months of treatment. Results At baseline, the HSV detection rate was 32%, without significant increase in genital HSV detection noted during the first month or the third month of ART. HIV-1 shedding declined during this period; no association was also noted between HSV and HIV-1 shedding during this period. Conclusion Because other studies have reported increased HSV detection in women initiating ART and we have previously reported an increase in GUD during early ART, it may be prudent to counsel HIV-1 infected women initiating ART that HSV shedding in the genital tract may continue after ART initiation. PMID:27683204

Genetic and phenotypic variations of inherited retinal diseases in dogs: the power of within- and across-breed studies

PubMed Central

Acland, Gregory M.

2014-01-01

Considerable clinical and molecular variations have been known in retinal blinding diseases in man and also in dogs. Different forms of retinal diseases occur in specific breed(s) caused by mutations segregating within each isolated breeding population. While molecular studies to find genes and mutations underlying retinal diseases in dogs have benefited largely from the phenotypic and genetic uniformity within a breed, within- and across-breed variations have often played a key role in elucidating the molecular basis. The increasing knowledge of phenotypic, allelic, and genetic heterogeneities in canine retinal degeneration has shown that the overall picture is rather more complicated than initially thought. Over the past 20 years, various approaches have been developed and tested to search for genes and mutations underlying genetic traits in dogs, depending on the availability of genetic tools and sample resources. Candidate gene, linkage analysis, and genome-wide association studies have so far identified 24 mutations in 18 genes underlying retinal diseases in at least 58 dog breeds. Many of these genes have been associated with retinal diseases in humans, thus providing opportunities to study the role in pathogenesis and in normal vision. Application in therapeutic interventions such as gene therapy has proven successful initially in a naturally occurring dog model followed by trials in human patients. Other genes whose human homologs have not been associated with retinal diseases are potential candidates to explain equivalent human diseases and contribute to the understanding of their function in vision. PMID:22065099

Genetic and phenotypic variations of inherited retinal diseases in dogs: the power of within- and across-breed studies.

PubMed

Miyadera, Keiko; Acland, Gregory M; Aguirre, Gustavo D

2012-02-01

Considerable clinical and molecular variations have been known in retinal blinding diseases in man and also in dogs. Different forms of retinal diseases occur in specific breed(s) caused by mutations segregating within each isolated breeding population. While molecular studies to find genes and mutations underlying retinal diseases in dogs have benefited largely from the phenotypic and genetic uniformity within a breed, within- and across-breed variations have often played a key role in elucidating the molecular basis. The increasing knowledge of phenotypic, allelic, and genetic heterogeneities in canine retinal degeneration has shown that the overall picture is rather more complicated than initially thought. Over the past 20 years, various approaches have been developed and tested to search for genes and mutations underlying genetic traits in dogs, depending on the availability of genetic tools and sample resources. Candidate gene, linkage analysis, and genome-wide association studies have so far identified 24 mutations in 18 genes underlying retinal diseases in at least 58 dog breeds. Many of these genes have been associated with retinal diseases in humans, thus providing opportunities to study the role in pathogenesis and in normal vision. Application in therapeutic interventions such as gene therapy has proven successful initially in a naturally occurring dog model followed by trials in human patients. Other genes whose human homologs have not been associated with retinal diseases are potential candidates to explain equivalent human diseases and contribute to the understanding of their function in vision.

[Nutritional impact of inflammatory bowel diseases on children and adolescents].

PubMed

dos Santos, Gilton Marques; Silva, Luciana Rodrigues; Santana, Genoile Oliveira

2014-12-01

To perform a systematic review of the literature about the nutritional impact of inflammatory bowel diseases in children and adolescents. A systematic review was performed using PubMed/MEDLINE, LILACS and SciELo databases, with inclusion of articles in Portuguese and in English with original data, that analyzed nutritional aspects of inflammatory bowel diseases in children and adolescents. The initial search used the terms "inflammatory bowel diseases" and "children" or "adolescents" and "nutritional evaluation" or "nutrition deficiency". The selection of studies was initially performed by reading the titles and abstracts. Review studies and those without data for pediatric patients were excluded. Subsequently, the full reading of the articles considered relevant was performed. 237 studies were identified, and 12 of them were selected according to the inclusion criteria. None of them was performed in South America. During the analysis of the studies, it was observed that nutritional characteristics of patients with inflammatory bowel disease may be altered; the main reports were related to malnutrition, growth stunting, delayed puberty and vitamin D deficiency. There are nutritional consequences of inflammatory bowel diseases in children and adolescents, mainly growth stunting, slower pubertal development, underweight and vitamin deficiencies. Nutritional impairments were more significant in patients with Crohn's disease; overweight and obesity were more common in patients with ulcerative rectocolitis. A detailed nutritional assessment should be performed periodically in children and adolescents with inflammatory bowel disease. Copyright © 2014 Associação de Pediatria de São Paulo. Publicado por Elsevier Editora Ltda. All rights reserved.

Are we there yet? Assessing achievement of vaccine-preventable disease goals in WHO's Western Pacific Region.

PubMed

Hennessey, Karen; Schluter, W William; Wang, Xiaojun; Boualam, Liliane; Jee, Youngmee; Mendoza-Aldana, Jorge; Roesel, Sigrun; Diorditsa, Sergey; Ehrenberg, John

2014-07-23

Accelerated disease control goals have long been appreciated for their role in galvanizing commitment and bringing a sense of urgency for disease prevention. WHO's Western Pacific Region has 14 on-going communicable disease reduction goals including 1 targeting eradication, 10 targeting elimination, and 3 control initiatives. These goals cover mother-to-child transmission of HIV, congenital syphilis, tuberculosis, leprosy, five parasitic diseases and four vaccine-preventable diseases (VPD). The initiatives have distinct objectives, approaches, and means in which to measure achievement of the goals. Given the long history and experience with VPD initiatives in the Western Pacific Region, this manuscript focuses on the Region's following initiatives: (1) smallpox eradication, (2) polio eradication, (3) measles elimination, (4) maternal and neonatal tetanus elimination (MNTE), and (5) hepatitis B control. There is good consistency across the Region's VPD initiatives yet a pattern of more robust and representative data requirements, stricter evaluation criteria, and more formal evaluation bodies are linked to the intensity of the goal - with eradication being the peak. On the other end of this spectrum, the Regional hepatitis B control initiative has established efficient and low-cost approaches for measuring impact and evaluating if the goals have been met. Even within the confines of VPD initiatives there are some deviations in use of terminology and comparisons across other disease control initiatives in the Region are provided. Copyright © 2014 World Health Organization. Published by Elsevier Ltd.. All rights reserved.

Etiological study of the short needle disease of pine

Treesearch

Francis A. Wood; Stanley P. Pennypacker

1976-01-01

The short needle disease of pines consists of dwarfing, crooking, twisting, and excessive elongation of random needles, failure of buds to develop, reduced lateral branch development and the premature casting of needles. The disease was initially associated with a power plant source of air pollution in the eastern United States during 1969; at that time the cause of...

75 FR 28626 - Disease, Disability, and Injury Prevention and Control Special Interest Projects (SIPs): SIP 10...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-05-21

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Centers for Disease Control and Prevention Disease, Disability, and Injury Prevention and Control Special Interest Projects (SIPs): SIP 10-029, Pilot Study--Cancer Survivorship Care Planning & SIP 10-030, Evaluating Special Events as a Recruitment Strategy for Cancer Screening, Initial Review In accordance...

Comparative efficacy of tilmicosin versus tulathromycin as a metaphylactic antimicrobial in feedlot calves at moderate risk for respiratory disease.

PubMed

Van Donkersgoed, Joyce; Merrill, John; Hendrick, Steven

2008-01-01

The purpose of this study was to compare the efficacy and cost-effectiveness of tilmicosin (MIC) versus tulathromycin (DRAX) as a metaphylactic antimicrobial in feedlot calves at moderate risk for bovine respiratory disease (BRD). Calves that received DRAX had significantly (P < or = .05) lower initial BRD treatment rates compared with calves that received MIC. However, there were no significant differences in the BRD relapse rate, railer rate, total mortality rate, BRD mortality rate, average daily gain, and dry matter conversion between the two groups. The economic advantage of the MIC group was Can$8.29/animal. Based on these results, while DRAX was more efficacious in reducing initial treatments for BRD in feedlot calves at moderate risk for disease, MIC was more cost-effective. The lower initial BRD treatment costs in the DRAX group did not offset the higher metaphylactic cost of DRAX.

Recognition and treatment of Alzheimer's disease: a case-based review.

PubMed

Marseille, Dana M; Silverman, Daniel H S

2006-01-01

Early recognition and treatment initiation are pivotal in managing Alzheimer's disease (AD). Once a diagnosis of AD is made, a treatment plan is developed and should include treatment initiation with cholinesterase inhibitors (ChEIs) to improve cognition, management of comorbid conditions, and treat behavioral symptoms. Caregiver compliance is integral to AD treatment success. The purpose of this report is to present two real case studies of "suspected" AD or related dementia and stress the significance of early and accurate diagnosis in disease management. In case 1, a caregiver reports gradual but progressive loss of memory, and the patient himself complains of memory impairment. Neuroimaging analysis confirms "typical " AD. In case 2, initiation of ChEI therapy is followed by substantial clinical improvement in the face of a complex medical picture, and neuroimaging revealing more neurodegenerative changes than could be accounted for by "pure" AD.

Distinct dynamic profiles of microglial activation are associated with progression of Alzheimer's disease.

PubMed

Hamelin, Lorraine; Lagarde, Julien; Dorothée, Guillaume; Potier, Marie Claude; Corlier, Fabian; Kuhnast, Bertrand; Caillé, Fabien; Dubois, Bruno; Fillon, Ludovic; Chupin, Marie; Bottlaender, Michel; Sarazin, Marie

2018-06-01

Although brain neuroinflammation may play an instrumental role in the pathophysiology of Alzheimer's disease, its actual impact on disease progression remains controversial, being reported as either detrimental or protective. This work aimed at investigating the temporal relationship between microglial activation and clinical progression of Alzheimer's disease. First, in a large cohort of patients with Alzheimer's disease we analysed the predictive value of microglial activation assessed by 18F-DPA-714 PET imaging on functional, cognitive and MRI biomarkers outcomes after a 2-year follow-up. Second, we analysed the longitudinal progression of 18F-DPA-714 binding in patients with Alzheimer's disease by comparison with controls, and assessed its influence on clinical progression. At baseline, all participants underwent a clinical assessment, brain MRI, 11C-PiB, 18F-DPA-714 PET imaging and TSPO genotyping. Participants were followed-up annually for 2 years. At the end of the study, subjects were asked to repeat a second 18F-DPA-714-PET imaging. Initial 18F-DPA-714 binding was higher in prodromal (n = 33) and in demented patients with Alzheimer's disease (n = 19) compared to controls (n = 17). After classifying patients into slow and fast decliners according to functional (Clinical Dementia Rating change) or cognitive (Mini-Mental State Examination score decline) outcomes, we found a higher initial 18F-DPA-714 binding in slow than fast decliners. Negative correlations were observed between initial 18F-DPA-714 binding and the Clinical Dementia Rating Sum of Boxes score increase, the MMSE score loss and the progression of hippocampal atrophy. This suggests that higher initial 18F-DPA-714 binding is associated with better clinical prognosis. Twenty-four patients with Alzheimer's disease and 15 control subjects performed a second DPA-PET. We observed an increase of 18F-DPA-714 in patients with Alzheimer's disease as compared with controls (mean 13.2% per year versus 4.2%) both at the prodromal (15.8%) and at the demented stages (8.3%). The positive correlations between change in 18F-DPA-714 binding over time and the three clinical outcome measures (Clinical Dementia Rating, Mini-Mental State Examination, hippocampal atrophy) suggested a detrimental effect on clinical Alzheimer's disease progression of increased neuroinflammation after the initial PET examination, without correlation with PiB-PET uptake at baseline. High initial 18F-DPA-714 binding was correlated with a low subsequent increase of microglial activation and favourable clinical evolution, whereas the opposite profile was observed when initial 18F-DPA-714 binding was low, independently of disease severity at baseline. Taken together, our results support a pathophysiological model involving two distinct profiles of microglial activation signatures with different dynamics, which differentially impact on disease progression and may vary depending on patients rather than disease stages.

Population characteristics of golden retriever lifetime study enrollees.

PubMed

Simpson, Melissa; Searfoss, Erin; Albright, Sharon; Brown, Diane E; Wolfe, Barbara; Clark, Nancy K; McCann, Susan E; Haworth, David; Guy, Mike; Page, Rod

2017-01-01

Studying cancer and other diseases poses a problem due to their protracted and multifactorial nature. Prospective studies are useful to investigate chronic disease processes since collection of lifestyle information, exposure data and co-incident health issues are collected before the condition manifests. The Golden Retriever Lifetime Study is one of the first prospective studies following privately-owned dogs throughout life to investigate the incidence and risk factors for disease outcomes, especially cancer.Owners of golden retrievers in the contiguous United States volunteered their dogs in early life. Owners and veterinarians complete online questionnaires about health status and lifestyle; dogs undergo a physical examination and collection of biological samples annually. The data presented summarize the initial study visits and the corresponding questionnaires for 3044 dogs in the cohort. The median age of dogs at enrollment was 14.0 months (interquartile range (IQR): 8-20 months). Approximately half of the population had undergone gonadectomy by their initial study visit. Medical conditions reported at enrollment consisted primarily of integumentary, gastrointestinal and urinary dysfunction. A large majority of the dogs have a record of having received preventive care (vaccines, parasiticides, flea and heartworm prevention) by the time of the initial study visit. Clinical pathology data were unremarkable. This study represents one of the first lifetime observational investigations in veterinary medicine. The population characteristics reported here indicate a healthy cohort of golden retrievers cared for by owners committed to their dogs' health. Data acquired over the study period will provide valuable information about genetic, dietary and environmental risk factors associated with disease in golden retrievers and a framework for future prospective studies in veterinary medicine.

Elevated Endothelial Hypoxia-Inducible Factor-1α Contributes to Glomerular Injury and Promotes Hypertensive Chronic Kidney Disease.

PubMed

Luo, Renna; Zhang, Weiru; Zhao, Cheng; Zhang, Yujin; Wu, Hongyu; Jin, Jianping; Zhang, Wenzheng; Grenz, Almut; Eltzschig, Holger K; Tao, Lijian; Kellems, Rodney E; Xia, Yang

2015-07-01

Hypertensive chronic kidney disease is one of the most prevalent medical conditions with high morbidity and mortality in the United States and worldwide. However, early events initiating the progression to hypertensive chronic kidney disease are poorly understood. We hypothesized that elevated endothelial hypoxia-inducible factor-1α (HIF-1α) is a common early insult triggering initial glomerular injury leading to hypertensive chronic kidney disease. To test our hypothesis, we used an angiotensin II infusion model of hypertensive chronic kidney disease to determine the specific cell type and mechanisms responsible for elevation of HIF-1α and its role in the progression of hypertensive chronic kidney disease. Genetic studies coupled with reverse transcription polymerase chain reaction profiling revealed that elevated endothelial HIF-1α is essential to initiate glomerular injury and progression to renal fibrosis by the transcriptional activation of genes encoding multiple vasoactive proteins. Mechanistically, we found that endothelial HIF-1α gene expression was induced by angiotensin II in a nuclear factor-κB-dependent manner. Finally, we discovered reciprocal positive transcriptional regulation of endothelial Hif-1α and Nf-κb genes is a key driving force for their persistent activation and disease progression. Overall, our findings revealed that the stimulation of HIF-1α gene expression in endothelial cells is detrimental to induce kidney injury, hypertension, and disease progression. Our findings highlight early diagnostic opportunities and therapeutic approaches for hypertensive chronic kidney disease. © 2015 American Heart Association, Inc.

76 FR 19996 - Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Funding...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-04-11

... Cohort of People with Lupus,'' FOA DP11-004, initial review. In accordance with Section 10(a)(2) of the... ``Longitudinal Study of a Population-based Cohort of People with Lupus,'' FOA DP11-004, initial review. Contact...

T regulatory cells in childhood asthma.

PubMed

Strickland, Deborah H; Holt, Patrick G

2011-09-01

Asthma is a chronic disease of the airways, most commonly driven by immuno-inflammatory responses to ubiquitous airborne antigens. Epidemiological studies have shown that disease is initiated early in life when the immune and respiratory systems are functionally immature and less able to maintain homeostasis in the face of continuous antigen challenge. Here, we examine the cellular and molecular mechanisms that underlie initial aeroallergen sensitization and the ensuing regulation of secondary responses to inhaled allergens in the airway mucosa. In particular, we focus on how T-regulatory (Treg) cells influence early asthma initiation and the potential of Treg cells as therapeutic targets for drug development in asthma. Copyright © 2011 Elsevier Ltd. All rights reserved.

Prognostic factors in pemphigus vulgaris and pemphigus foliaceus.

PubMed

Saha, M; Bhogal, B; Black, M M; Cooper, D; Vaughan, R W; Groves, R W

2014-01-01

Pemphigus typically has a chronic course, although there is great variability in disease duration (DD) and time taken to disease remission (DR) between individuals with the disease. The reasons for this are unclear. To explore the prognostic influence of epidemiological, clinical, immunological and genetic factors on disease course and remission in pemphigus vulgaris (PV) and pemphigus foliaceus (PF). This was a retrospective study of patients with PV and PF, recruited from a single UK centre. Direct and indirect immunofluorescence and enzyme-linked immunosorbent assay studies for antidesmoglein (Dsg) antibodies were used to assess immunological factors. Polymerase chain reaction with sequence specific primers (PCR-SSP) was used to assess the Class II human leukocyte antigen status of patients. Prognostic endpoints investigated were time to initial first DR and total DD. Ninety-five patients were recruited (79 PV and 16 PF). Patients of Indo-Asian origin were significantly associated with longer DD than White-British patients (P = 0.029). In addition, younger age at onset was associated with a worse prognosis in terms of DD: the mean age at presentation of patients with DD of < 5 years was 49 years (SEM = 3.4) compared with 40 years (SEM = 1.9) in those with DD > 5 years (P = 0.039). A higher initial intercellular antibody titre on normal human skin substrate was associated with a greater time to initial DR (P = 0.007) and high anti-Dsg 3 levels at baseline were associated with a longer total DD (P = 0.03). Ethnic group, age at presentation, initial intercellular antibody titre and initial Dsg 3 antibody levels all had a significant impact on prognosis of pemphigus. © 2013 British Association of Dermatologists.

78 FR 9063 - National Institute of Diabetes and Digestive and Kidney Diseases; Notice of Meetings

Federal Register 2010, 2011, 2012, 2013, 2014

2013-02-07

... Diabetes and Digestive and Kidney Diseases; Notice of Meetings Pursuant to section 10(d) of the Federal... Digestive and Kidney Diseases Initial Review Group; Kidney, Urologic and Hematologic Diseases D Subcommittee... . Name of Committee: National Institute of Diabetes and Digestive and Kidney Diseases Initial Review...

Trends in chronic diseases among the oldest-old in China

NASA Astrophysics Data System (ADS)

Teh, Jane K. L.; Tey, Nai Peng

2015-12-01

This study examined the prevalence of several chronic diseases among the oldest-old in China. Data came from the Chinese Longitudinal Healthy Longevity Survey (CLHLS) of 4 waves collected in 2002, 2005, 2008 and 2011, filtered to include individuals aged 80 and above. Bivariate and logistic regression methods were used in analyses. There were significant differences in the prevalence of hypertension, diabetes, chronic heart diseases, stroke/cardiovascular diseases, cancer and dementia, which generally saw an increase across the 4 waves. By contrast, prevalence of Parkinson was not significantly different over the 4 waves. Logistic regression results revealed that since 2002, hypertension had been significantly higher in subsequent waves in 2005, 2008 and 2011. Stroke had also shown significant increase in the 2008 and 2011 waves. Other chronic diseases such as diabetes, heart disease, cancer, Parkinson and dementia were only found to be significantly higher in the recent 2011 wave compared to the initial wave in 2002. Arthritis, which initially increased in earlier waves, had dropped significantly in the recent 2011 wave. However, respiratory conditions had been significantly lower since the initial wave in 2002. Generally, findings confirmed the increasing trend of chronic morbidity in recent years among the oldest-old in China. Long life expectancy coupled with chronic morbidity in very late age will duly have societal and economic implications.

Nationwide survey on the 2005 Guidelines for the Management of Community-Acquired Adult Pneumonia: validation of differentiation between bacterial pneumonia and atypical pneumonia.

PubMed

Watanabe, Akira; Goto, Hajime; Kohno, Shigeru; Matsushima, Toshiharu; Abe, Shosaku; Aoki, Nobuki; Shimokata, Kaoru; Mikasa, Keiichi; Niki, Yoshihito

2012-03-01

The Japanese Respiratory Society Guidelines for the Management of Community-Acquired Pneumonia (CAP) in Adults (JRS 2005) was published as a revision of the Basic Concept for the Management of CAP in Adults (JRS 2000). To evaluate the JRS 2005 criteria for differentiating between disease types and assessing the status of antimicrobial agent use in initial treatment, we conducted a prospective survey. The survey was conducted from July 2006 to March 2007 as a nationwide joint study by 200 institutions. The study subjects included patients aged ≥16 years of age who had CAP, and patients who met the inclusion criteria were consecutively enrolled. Disease type differentiation based on JRS 2005 and JRS 2000 was conducted. Disease type diagnosis was also performed based on test results. The sensitivity and specificity of disease type differentiation were calculated. The antimicrobial agents used in the initial treatment were classified as recommended or non-recommended based on JRS 2005. The validity of non-recommended antimicrobial agent use was investigated. A total of 1875 patients were analyzed. Differentiation of atypical pneumonia using the JRS 2005 criteria had higher sensitivity and lower specificity than differentiation using the JRS 2000 criteria. The antimicrobial agents recommended by JRS 2005 were used as initial treatment in a low number of cases. The efficacy of the recommended antimicrobial agents was similar to that of the non-recommended agents. JRS 2005 is advantageous in terms of reducing the number of items used in disease type differentiation. The recommended antimicrobial agents used for the initial treatment are believed to be appropriate. Copyright © 2012 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.

Cumulative Risk for Early Sexual Initiation among American Indian Youth: A Discrete-Time Survival Analysis

ERIC Educational Resources Information Center

Mitchell, Christina M.; Whitesell, Nancy Rumbaugh; Spicer, Paul; Beals, Janette; Kaufman, Carol E.

2007-01-01

Approximately 3 million teens are diagnosed with a sexually transmitted disease (STD) annually; STDs rates for American Indian young adults are among the highest of any racial/ethnic group. An important risk factor for STDs is early initiation of sex. In this study, we examined risk for early initiation with 474 American Indian youth ages 14-18,…

Daily Physical Activity for Children and Youth: A Review and Synthesis of the Literature

ERIC Educational Resources Information Center

Bates, Heidi

2006-01-01

A Daily Physical Activity (DPA) Initiative was implemented in all schools in Alberta starting in September 2005. The expected outcome of the DPA Initiative is to increase the activity levels and healthy habits of students and, in part, address related issues such as chronic disease. As part of the first tier of the DPA Initiative evaluation study,…

Colorectal cancer complicating Crohn's disease.

PubMed

Freeman, H J

2001-04-01

Some earlier studies have indicated that patients with inflammatory bowel disease, especially those with long-standing and extensive ulcerative colitis, have an increased risk of colorectal cancer. Moreover, others in tertiary care centres have suggested that patients with Crohn's disease also have a higher risk of colorectal cancer. Canadian data on colorectal cancer in Crohn's disease appear to be limited. For this investigation, a single clinician database of 877 patients with Crohn's disease was used. Altogether, there were six patients with colorectal cancer (ie, overall rate of 0.7%). All of these patients were men with an initial diagnosis of Crohn's disease established at a mean age of approximately 28 years, with either ileocolonic disease or colonic disease alone, but not with ileal disease alone. Although there was a predominance of women in the overall study population (ie, 56.1%), no women developed colorectal cancer. The clinical behaviour of Crohn's disease was classified as nonstricturing in all six patients with colorectal cancer, but in two patients, Crohn's disease was complicated by a perirectal abscess or a fistula. All cancers were located in the rectum and were diagnosed 30 years, 22 years, seven years, 18 years, 20 years and 40 years after Crohn's disease was initially diagnosed. In three patients, the cancer was detected in a residual rectal stump after a partial colon resection at least 10 years earlier. In five patients, localized extension of disease through the serosa, nodal or distant metastases (ie, liver, lung) was found at the time of cancer diagnosis; two patients have since died. The present study confirms that Crohn's disease involving the colon may be a possible risk factor for the development of colorectal cancer, at least in younger men, but, in this study, not in women. However, part of this increased risk in men may have been related to the presence of a rectal stump, rather than to Crohn's disease per se.

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.

Heart Failure and Frailty in the Community-Living Elderly Population: What the UFO Study Will Tell Us.

PubMed

Fung, Erik; Hui, Elsie; Yang, Xiaobo; Lui, Leong T; Cheng, King F; Li, Qi; Fan, Yiting; Sahota, Daljit S; Ma, Bosco H M; Lee, Jenny S W; Lee, Alex P W; Woo, Jean

2018-01-01

Heart failure and frailty are clinical syndromes that present with overlapping phenotypic characteristics. Importantly, their co-presence is associated with increased mortality and morbidity. While mechanical and electrical device therapies for heart failure are vital for select patients with advanced stage disease, the majority of patients and especially those with undiagnosed heart failure would benefit from early disease detection and prompt initiation of guideline-directed medical therapies. In this article, we review the problematic interactions between heart failure and frailty, introduce a focused cardiac screening program for community-living elderly initiated by a mobile communication device app leading to the Undiagnosed heart Failure in frail Older individuals (UFO) study, and discuss how the knowledge of pre-frailty and frailty status could be exploited for the detection of previously undiagnosed heart failure or advanced cardiac disease. The widespread use of mobile devices coupled with increasing availability of novel, effective medical and minimally invasive therapies have incentivized new approaches to heart failure case finding and disease management.

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.

Evidence of major genes for resistance to bacterial cold-water disease in rainbow trout using mixed inheritance multiple-threshold models and Bayesian segregation analysis

USDA-ARS?s Scientific Manuscript database

PURPOSE: Bacterial cold water disease (BCWD) causes significant economic loss in salmonid aquaculture, and in 2005, a rainbow trout breeding program was initiated at the NCCCWA to select for increased disease survival. The main objectives of this study were to determine the mode of inheritance of di...

Predicting factors of fistula healing and clinical remission after infliximab-based combined therapy for perianal fistulizing Crohn's disease.

PubMed

Tougeron, David; Savoye, Guillaume; Savoye-Collet, Céline; Koning, Edith; Michot, Francis; Lerebours, Eric

2009-08-01

Perianal fistulizing Crohn's disease (PFCD) treatment is based on fistula drainage, antibiotics, immunosuppressant (IS) drugs, and infliximab. Our aim was to study the effectiveness of combination therapy on PFCD and to search for clinical or imaging features associated with the initial complete clinical response and its stability overtime. All patients with PFCD treated in our tertiary center between 2000 and 2005 by infliximab in combination with seton placement and/or IS and evaluated by MRI before treatment were included in the study. Basal clinical and MRI characteristics were recorded. Response to treatment was evaluated after the infliximab induction regiment and at the end of the follow-up. Twenty-six patients were included and followed-up for an average 4.9 years. A complex fistula was present in 69% (18/26 patients) of cases and eight (8/26 patients) had an ano-vaginal fistula. After infliximab induction therapy, 13 patients (50%) achieved a complete clinical response. The initial clinical response was significantly associated with the absence of both, active intestinal disease (54% vs. 8%, P = 0.03) and active proctitis (77% vs. 23%, P = 0.01). No initial MRI characteristics were linked to the initial response. In multivariate analysis, only the presence of active proctitis was associated with the lack of response (P = 0.047). At the end of the follow-up, 42% of the patients remained in clinical remission. No clinical characteristics were associated to sustained response when among long-standing responders two exhibited a normal post-treatment MRI. An initial complete response of PFCD was observed in half of the patients after combined therapy including infliximab that decreased to 42% later on. Complete healing of fistulas on MRI was possible but unusual. The initial response seemed related to the absence of active intestinal disease, especially in the rectum, when the long-term response could not be predicted by the basal characteristics of patients.

78 FR 41939 - National Institute of Allergy and Infectious Diseases; Notice of Closed Meetings

Federal Register 2010, 2011, 2012, 2013, 2014

2013-07-12

... Allergy and Infectious Diseases; Notice of Closed Meetings Pursuant to section 10(d) of the Federal... Infectious Diseases Special Emphasis Panel; NIAID Investigator Initiated Program Project Applications. Date... Allergy and Infectious Diseases Special Emphasis Panel; NIAID Investigator Initiated Program Project...

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

Federal Register 2010, 2011, 2012, 2013, 2014

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...

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.

Comparison of primary and reoperative surgery in patients with Crohns disease.

PubMed

Heimann, T M; Greenstein, A J; Lewis, B; Kaufman, D; Heimann, D M; Aufses, A H

1998-04-01

This study was performed to determine the clinical results of patients with Crohns disease who require surgical resection. The outcome of patients undergoing initial surgery was compared with those having reoperation. One hundred sixty-four patients undergoing intestinal resection for Crohns disease at The Mount Sinai Hospital from 1976 to 1989 were studied prospectively. The mean duration of follow-up was 72 months. Ninety patients (55%) underwent initial intestinal resection whereas 74 patients (45%) underwent reoperation for recurrent disease. Patients undergoing reoperation were older (33.4 vs. 38.7 years), had longer durations of disease (8.7 vs. 15.2 years), had shorter resections (60 vs. 46 cm), and were more likely to require ileostomy. Forty-seven percent of the patients with multiple previous resections required an ileostomy. This group also received a mean of 2.3 U blood in the perioperative period and showed a trend to increased symptomatic recurrence (49% vs. 71% at 5 years). Patients with Crohns disease undergoing first and second reoperation have outcomes similar to those in patients undergoing primary resection. Patients requiring multiple reoperations are more likely to require blood transfusions and permanent ileostomy and to show a greater trend to early symptomatic recurrence.

Evaluation of disease progression in INCL by MR spectroscopy

PubMed Central

Baker, Eva H; Levin, Sondra W; Zhang, Zhongjian; Mukherjee, Anil B

2015-01-01

Objective Infantile neuronal ceroid lipofuscinosis (INCL) is a devastating neurodegenerative storage disease caused by palmitoyl-protein thioesterase-1 deficiency, which impairs degradation of palmitoylated proteins (constituents of ceroid) by lysosomal hydrolases. Consequent lysosomal ceroid accumulation leads to neuronal injury. As part of a pilot study to evaluate treatment benefits of cysteamine bitartrate and N-acetylcysteine, we quantitatively measured brain metabolite levels using magnetic resonance spectroscopy (MRS). Methods A subset of two patients from a larger treatment and follow-up study underwent serial quantitative single-voxel MRS examinations of five anatomical sites. Three echo times were acquired in order to estimate metabolite T2. Measured metabolite levels included correction for partial volume of cerebrospinal fluid. Comparison of INCL patients was made to a reference group composed of asymptomatic and minimally symptomatic Niemann-Pick disease type C patients. Results In INCL patients, N-acetylaspartate (NAA) was abnormally low at all locations upon initial measurement, and further declined throughout the follow-up period. In the cerebrum (affected early in the disease course), choline and myo-inositol were initially elevated and fell during the follow-up period, whereas in the cerebellum and brainstem (affected later), choline and myo-inositol were initially normal and rose subsequently. Interpretation Choline and myo-inositol levels in our patients are consistent with patterns of neuroinflammation observed in two INCL mouse models. Low, persistently declining NAA was expected based on the progressive, irreversible nature of the disease. Progression of metabolite levels in INCL has not been previously quantified; therefore the results of this study serve as a reference for quantitative evaluation of future therapeutic interventions. PMID:26339674

Lower Anogenital Tract Disease Therapy Outcomes, COMET, and CROWN: Call for Research Submissions.

PubMed

Andrews, Jeffrey

2015-10-01

There is a problem of inconsistent and inappropriate outcome selection for research studies. We can improve the relevance of research results for women and for their physicians and clinicians by encouraging researchers to critically evaluate outcome measures, and use valid, appropriate, standardized measures. To this purpose, and to facilitate synthesis of the evidence, outcomes reported by clinical studies should be standardized for different disease conditions through the development of core outcome sets (COS). There is an international effort for reaching consensus on outcome measures and establishing COS that represent agreed-upon standardized collections of outcome measures that will be reported in all studies within a clinical area. Across clinical specialties, the Core Outcome Measures in Effectiveness Trials (COMET) initiative launched in 2010. In 2014, the editors of women's health journals answered the challenge of COMET and formed the Core Outcomes in Women's Health initiative. The Journal of Lower Genital Tract Diseases is a participating member of the Core Outcomes in Women's Health consortium. There is broad inconsistency in outcome measures and reporting in the field of lower anogenital tract diseases. No core outcome sets currently exist. Suggested target conditions in anogenital disease are vulvar dermatoses, cervical intraepithelial neoplasia, and vulvodynia. Investigators are encouraged to conduct secondary systematic research to determine previously reported primary outcome measures and suggest domains for COS. Core Outcomes in Women's health initiative and COMET encourage the formation of consensus panels of stakeholders (researchers, health care providers, patients, and others) to recommend outcome domains and COS and then publish their report.

Evaluation of disease progression in INCL by MR spectroscopy.

PubMed

Baker, Eva H; Levin, Sondra W; Zhang, Zhongjian; Mukherjee, Anil B

2015-08-01

Infantile neuronal ceroid lipofuscinosis (INCL) is a devastating neurodegenerative storage disease caused by palmitoyl-protein thioesterase-1 deficiency, which impairs degradation of palmitoylated proteins (constituents of ceroid) by lysosomal hydrolases. Consequent lysosomal ceroid accumulation leads to neuronal injury. As part of a pilot study to evaluate treatment benefits of cysteamine bitartrate and N-acetylcysteine, we quantitatively measured brain metabolite levels using magnetic resonance spectroscopy (MRS). A subset of two patients from a larger treatment and follow-up study underwent serial quantitative single-voxel MRS examinations of five anatomical sites. Three echo times were acquired in order to estimate metabolite T2. Measured metabolite levels included correction for partial volume of cerebrospinal fluid. Comparison of INCL patients was made to a reference group composed of asymptomatic and minimally symptomatic Niemann-Pick disease type C patients. In INCL patients, N-acetylaspartate (NAA) was abnormally low at all locations upon initial measurement, and further declined throughout the follow-up period. In the cerebrum (affected early in the disease course), choline and myo-inositol were initially elevated and fell during the follow-up period, whereas in the cerebellum and brainstem (affected later), choline and myo-inositol were initially normal and rose subsequently. Choline and myo-inositol levels in our patients are consistent with patterns of neuroinflammation observed in two INCL mouse models. Low, persistently declining NAA was expected based on the progressive, irreversible nature of the disease. Progression of metabolite levels in INCL has not been previously quantified; therefore the results of this study serve as a reference for quantitative evaluation of future therapeutic interventions.

Mineral Metabolites, Angiotensin II Inhibition and Outcomes in Advanced Chronic Kidney Disease.

PubMed

Jovanovich, Anna J; Chonchol, Michel B; Sobhi, Atousa; Kendrick, Jessica B; Cheung, Alfred K; Kaufman, James S; Smits, Gerard; Jablonski, Kristen L

2015-01-01

Evidence suggests that the renin-angiotensin-aldosterone system (RAAS) interacts with the vitamin D-fibroblast growth factor 23-Klotho axis. We investigated whether circulating mineral metabolism markers modify outcomes in response to RAAS inhibition in subjects with advanced chronic kidney disease (CKD). In this retrospective cohort study, we analyzed the association of angiotensin-converting enzyme inhibitor (ACEI) and angiotensin receptor blocker (ARB) use with all-cause mortality and dialysis initiation among 1,753 subjects (1,099 CKD, estimated glomerular filtration rate 18 ± 6 ml/min/1.73 m(2) and 654 end-stage renal disease [ESRD]) from the Homocysteine in Kidney and End Stage Renal Disease (HOST) study. A propensity score analysis accounted for indication bias and Cox regression models adjusted for mineral metabolism markers. Mean follow-up was 3.2 years; 714 (41%) subjects died and 615 (56%) initiated dialysis. In adjusted analyses, all subjects treated with ACEI/ARB had a significantly lower hazard of death (hazards ratio (HR) 0.81, 95% CI 0.70-0.95, p = 0.007). Those with CKD not on dialysis and treated with ACEI/ARB trended toward a lower hazard of dialysis initiation (HR 0.86, 95% CI 0.73-1.01, p = 0.06). The association with mortality did not differ by level of mineral metabolism marker (p for interaction >0.16); however, the relationship with dialysis initiation differed according to the median serum phosphorus level (p for interaction <0.001). RAAS inhibition was associated with decreased all-cause mortality independent of disordered mineral metabolism among mostly male HOST subjects with advanced CKD and ESRD. However, among those with CKD not requiring dialysis, the renoprotection associated with RAAS inhibition was attenuated by higher serum phosphorus levels. Further studies are needed to confirm this association. © 2015 S. Karger AG, Basel.

Motor Symptoms at Onset of Parkinson Disease and Risk for Cognitive Impairment and Depression

PubMed Central

Dewey, Richard B.; Taneja, Aanchal; McClintock, Shawn M.; Cullum, C. Munro; Dewey, Richard B.; Bernstein, Ira; Husain, Mustafa M.

2012-01-01

Objective To determine if side and type of initial motor symptoms in Parkinson disease predict risk for later development of cognitive impairment or depressive symptoms. Methods We recruited 124 nondemented patients with Parkinson disease to participate in a cohort study of cognitive function and depressive symptoms that used validated neuropsychological tests and a depressive symptom inventory. We first reviewed the patients’ charts to determine their initial motor symptom and side of onset, and then classified the patients into 4 groups: right-side onset tremor, right-side onset bradykinesia/rigidity, left-side onset tremor, and left-side onset bradykinesia/rigidity. We excluded patients with bilateral symptom onset. We used analysis of variance on neuropsychological test performance and depressive symptoms to determine if group classification affected risk of cognitive impairment or depressive symptoms. We controlled our analyses for disease duration and motor severity as measured by the Unified Parkinson Disease Rating Scale Part III motor score. Results There were no differences in any cognitive measure by side and type of initial motor symptoms. The right-side onset tremor group had the lowest depressive symptom scores, and no patient in any group reported severe depressive symptoms. Conclusion Our findings suggest that patterns of nigral cell loss correlating to the initial side and type of motor symptoms in Parkinson disease are not related to the risk of later cognitive impairment. By contrast, patients with right-side onset of tremor appear to have a lower risk of depressive symptoms than patients with other presentations. PMID:22960435

First record of black band disease in the Hawaiian archipelago: response, outbreak, status, virulence, and a method of treatment

USGS Publications Warehouse

Aeby, Greta S.; Work, Thierry M.; Runyon, Christina M.; Shore-Maggio, Amanda; Ushijima, Blake; Videau, Patrick; Beurmann, Silvia; Callahan, Sean M.

2015-01-01

A high number of coral colonies, Montipora spp., with progressive tissue loss were reported from the north shore of Kaua‘i by a member of the Eyes of the Reef volunteer reporting network. The disease has a distinct lesion (semi-circular pattern of tissue loss with an adjacent dark band) that was first observed in Hanalei Bay, Kaua‘i in 2004. The disease, initially termedMontipora banded tissue loss, appeared grossly similar to black band disease (BBD), which affects corals worldwide. Following the initial report, a rapid response was initiated as outlined in Hawai‘i’s rapid response contingency plan to determine outbreak status and investigate the disease. Our study identified the three dominant bacterial constituents indicative of BBD (filamentous cyanobacteria, sulfate-reducing bacteria, sulfide-oxidizing bacteria) in coral disease lesions from Kaua‘i, which provided the first evidence of BBD in the Hawaiian archipelago. A rapid survey at the alleged outbreak site found disease to affect 6-7% of the montiporids, which is higher than a prior prevalence of less than 1% measured on Kaua‘i in 2004, indicative of an epizootic. Tagged colonies with BBD had an average rate of tissue loss of 5.7 cm2/day over a two-month period. Treatment of diseased colonies with a double band of marine epoxy, mixed with chlorine powder, effectively reduced colony mortality. Within two months, treated colonies lost an average of 30% less tissue compared to untreated controls.

Factors Associated with Timing of Initiation of Antiretroviral Therapy among HIV-1 Infected Adults in the Niger Delta Region of Nigeria

PubMed Central

Ogoina, Dimie

2015-01-01

Introduction Based on growing evidence mainly from countries outside Sub-Saharan Africa, the World Health Organisation (WHO) now recommends initiation of antiretroviral therapy (ART) in HIV-infected individuals in developing countries when CD4 cell count (CD4+) is ≤ 500cells/ul. Nigeria accounts for about 14% of the estimated HIV/AIDS burden in Sub-Saharan Africa. We evaluated the factors associated with timing of initiation of ART among treatment-ineligible HIV-infected adults from Nigeria. Methods We retrospectively reviewed the hospital records of ART ineligible HIV-infected adults who enrolled into HIV care between January 2008 and December 2012 at two major tertiary hospitals in Bayelsa State, South-South Nigeria. Demographic, clinical and laboratories data were obtained at presentation, at each subsequent visit at 6 monthly intervals and at time of initiation of ART. Cox proportional regression and Kaplan-Meier survival analysis were used to evaluate independent predictors of time to initiation of ART. Results Amongst the 280 study participants, 70.6% were females, 62.6% had CD4+ ≥500cells/ul, 48.4% had WHO HIV Stage 1 disease and 34.3% were lost to follow up. In a cohort of 180 participants followed up for ≥3months, participants with CD4+ of 351-500cells/ul and stage 2 disease were more likely to start ART earlier than those with CD4+ > 500cells/ul (Hazard ratio [HR]-1.7, 95% confidence interval [CI] of 1.0-2.9) and stage 1 disease (HR-2.3 (95% CI-1.3-4.2) respectively. HIV-infected adults with faster CD4+ decay required earlier ART initiation, especially in the first year of follow up. Conclusion ART-ineligible HIV-infected adults on follow up in South-South Nigeria are more likely to require earlier initiation of ART if they have stage 2 HIV disease or CD4+ ≤500cells/ul at presentation. Our findings suggest faster progression of HIV-disease in these groups of individuals and corroborate the growing evidence in support for earlier initiation of ART. PMID:25933356

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

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

Federal Register 2010, 2011, 2012, 2013, 2014

2012-05-22

... 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...

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...), the Centers for Disease Control and Prevention (CDC) announces the aforementioned meeting: Time and...

76 FR 75552 - National Institute of Allergy and Infectious Diseases; Notice of Closed Meetings

Federal Register 2010, 2011, 2012, 2013, 2014

2011-12-02

... Allergy and Infectious Diseases; Notice of Closed Meetings Pursuant to section 10(d) of the Federal... Institute of Allergy and Infectious Diseases Special Emphasis Panel, NIAID Investigator Initiated Program... Institute of Allergy and Infectious Diseases Special Emphasis Panel, NIAID Investigator Initiated Program...

77 FR 56660 - National Institute of Allergy and Infectious Diseases; Notice of Closed Meetings

Federal Register 2010, 2011, 2012, 2013, 2014

2012-09-13

... constitute a clearly unwarranted invasion of personal privacy. Name of Committee: Microbiology, Infectious Diseases and AIDS Initial Review Group; Microbiology and Infectious Diseases B Subcommittee. MID-B October..., [email protected] . Name of Committee: Microbiology, Infectious Diseases and AIDS Initial Review Group...

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. Restoration of euthyroidism will lower the blood glucose level.

Antiretroviral therapy CNS penetration and HIV-1–associated CNS disease

PubMed Central

Winston, A.; Walsh, J.; Post, F.; Porter, K.; Gazzard, B.; Fisher, M.; Leen, C.; Pillay, D.; Hill, T.; Johnson, M.; Gilson, R.; Anderson, J.; Easterbrook, P.; Bansi, L.; Orkin, C.; Ainsworth, J.; Palfreeman, A.; Gompels, M.; Phillips, A.N.; Sabin, C.A.

2011-01-01

Objective: The impact of different antiretroviral agents on the risk of developing or surviving CNS disease remains unknown. The aim of this study was to investigate whether using antiretroviral regimens with higher CNS penetration effectiveness (CPE) scores was associated with reduced incidence of CNS disease and improved survival in the UK Collaborative HIV Cohort (CHIC) Study. Methods: Adults without previous CNS disease, who commenced combination antiretroviral therapy (cART) between 1996 and 2008, were included (n = 22,356). Initial and most recent cART CPE scores were calculated. CNS diseases were HIV encephalopathy (HIVe), progressive multifocal leukoencephalopathy (PML), cerebral toxoplasmosis (TOXO), and cryptococcal meningitis (CRYPTO). Incidence rates and overall survival were stratified by CPE score. A multivariable Poisson regression model was used to identify independent associations. Results: The median (interquartile range) CPE score for initial cART regimen increased from 7 (5–8) in 1996–1997 to 9 (8–10) in 2000–2001 and subsequently declined to 6 (7–8) in 2006–2008. Differences in gender, HIV acquisition risk group, and ethnicity existed between CPE score strata. A total of 251 subjects were diagnosed with a CNS disease (HIVe 80; TOXO 59; CRYPTO 56; PML 54). CNS diseases occurred more frequently in subjects prescribed regimens with CPE scores ≤4, and less frequently in those with scores ≥10; however, these differences were nonsignificant. Initial and most recent cART CPE scores ≤4 were independently associated with increased risk of death. Conclusion: Clinical status at time of commencing cART influences antiretroviral selection and CPE score. This information should be considered when utilizing CPE scores for retrospective analyses. PMID:21339496

The Translation of Health Research in Kinesiology

ERIC Educational Resources Information Center

Ainsworth, Barbara E.

2009-01-01

The translation of health research is a process of transforming scientific discoveries arising from laboratory, clinical, or population studies into clinical or population-based applications to improve health by reducing disease incidence, morbidity, and mortality. Initiated by the National Institutes for Health Roadmap Initiative and the U.S.…

Loss of ability to work and ability to live independently in Parkinson's disease.

PubMed

Jasinska-Myga, Barbara; Heckman, Michael G; Wider, Christian; Putzke, John D; Wszolek, Zbigniew K; Uitti, Ryan J

2012-02-01

Ability to work and live independently is of particular concern for patients with Parkinson's disease (PD). We studied a series of PD patients able to work or live independently at baseline, and evaluated potential risk factors for two separate outcomes: loss of ability to work and loss of ability to live independently. The series comprised 495 PD patients followed prospectively. Ability to work and ability to live independently were based on clinical interview and examination. Cox regression models adjusted for age and disease duration were used to evaluate associations of baseline characteristics with loss of ability to work and loss of ability to live independently. Higher UPDRS dyskinesia score, UPDRS instability score, UPDRS total score, Hoehn and Yahr stage, and presence of intellectual impairment at baseline were all associated with increased risk of future loss of ability to work and loss of ability to live independently (P ≤ 0.0033). Five years after initial visit, for patients ≤70 years of age with a disease duration ≤4 years at initial visit, 88% were still able to work and 90% to live independently. These estimates worsened as age and disease duration at initial visit increased; for patients >70 years of age with a disease duration >4 years, estimates at 5 years were 43% able to work and 57% able to live independently. The information provided in this study can offer useful information for PD patients in preparing for future ability to perform activities of daily living. Copyright © 2011 Elsevier Ltd. All rights reserved.

Salt reduction in China: a state-of-the-art review

PubMed Central

Shao, Shuai; Hua, Yechu; Yang, Ying; Liu, Xiaojuan; Fan, Jingruo; Zhang, An; Xiang, Jingling; Li, Mingjing; Yan, Lijing L

2017-01-01

Objective This study aimed to reveal the latest evidence on salt reduction initiatives in China in order to identify the contextual cost-effective interventions, as well as the barriers encountered during China’s long march to reach its population salt reduction goal. Background Population-based salt reduction has been considered as one of the most cost-effective strategies in the world for the prevention and control of noncommunicable diseases. China, along with its sustained economic growth, faces increasing burdens from chronic diseases such as cardiovascular and kidney diseases. With policy support and cross-sector collaboration, various salt reduction initiatives have been adopted in China in order to reduce such dietary risk, especially since the beginning of this millennium. Methods This study conducted structured literature reviews in both English and Chinese databases and synthesized the latest evidence on the association of salt intake and health, as well as salt intake among Chinese and population-based salt reduction strategies in China and around the world. Findings Dietary salt restriction has been found to contribute to the reduction of blood pressure among both the normotensives and hypertensives bringing associated reduced disease burdens and great public health benefits. With gender, ethnic, and regional variations, salt intake levels in the population in China are well above the recommended threshold and physiological need. Admittedly, excessive salt intake precipitates the high prevalence of hypertension and cardiovascular disease among the Chinese. Considering that the majority of the dietary salt is added during cooking in China, salt substitutes, salt restriction tools, and health education are the most common salt reduction initiatives with varying levels of effectiveness and acceptability among the Chinese population. Implication Overwhelming evidence is in support of a well-coordinated nationwide salt restriction initiative as a key public health strategy for the prevention and control of hypertension and its related diseases. Orchestrated efforts from the government, industries, academia, health professionals, and the general public are required to achieve China’s long-term goal for salt reduction. PMID:28260957

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

Federal Register 2010, 2011, 2012, 2013, 2014

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...

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.

A Case of Sporadic Creutzfeldt-Jakob Disease Presenting as Conversion Disorder.

PubMed

Yegya-Raman, Nikhil; Aziz, Rehan; Schneider, Daniel; Tobia, Anthony; Leitch, Megan; Nwobi, Onyi

2017-01-01

Background . Creutzfeldt-Jakob disease is a rare disorder of the central nervous system. Its initial diagnosis may be obscured by its variable presentation. This case report illustrates the complexity of diagnosing this disease early in the clinical course, especially when the initial symptoms may be psychiatric. It offers a brief review of the literature and reinforces a role for consultation psychiatry services. Methods . PUBMED/MEDLINE was searched using the terms "Creutzfeldt-Jakob disease", "psychiatric symptoms", "conversion disorder", "somatic symptom disorder", "functional movement disorder", and "functional neurologic disorder". Case . The patient was a 64-year-old woman with no prior psychiatric history who was initially diagnosed with conversion disorder and unspecified anxiety disorder but soon thereafter was discovered to have Creutzfeldt-Jakob disease. Discussion . This case highlights the central role of psychiatric symptoms in early presentations of Creutzfeldt-Jakob disease. Still, few other cases in the literature report functional neurological symptoms as an initial sign. The consultation psychiatrist must remain alert to changing clinical symptoms, especially with uncharacteristic disease presentations.

A Scientometric Evaluation of the Chagas Disease Implementation Research Programme of the PAHO and TDR

PubMed Central

Carbajal-de-la-Fuente, Ana Laura; Yadón, Zaida E.

2013-01-01

The Special Programme for Research and Training in Tropical Diseases (TDR) is an independent global programme of scientific collaboration cosponsored by the United Nations Children's Fund, the United Nations Development Program, the World Bank, and the World Health Organization. TDR's strategy is based on stewardship for research on infectious diseases of poverty, empowerment of endemic countries, research on neglected priority needs, and the promotion of scientific collaboration influencing global efforts to combat major tropical diseases. In 2001, in view of the achievements obtained in the reduction of transmission of Chagas disease through the Southern Cone Initiative and the improvement in Chagas disease control activities in some countries of the Andean and the Central American Initiatives, TDR transferred the Chagas Disease Implementation Research Programme (CIRP) to the Communicable Diseases Unit of the Pan American Health Organization (CD/PAHO). This paper presents a scientometric evaluation of the 73 projects from 18 Latin American and European countries that were granted by CIRP/PAHO/TDR between 1997 and 2007. We analyzed all final reports of the funded projects and scientific publications, technical reports, and human resource training activities derived from them. Results about the number of projects funded, countries and institutions involved, gender analysis, number of published papers in indexed scientific journals, main topics funded, patents inscribed, and triatomine species studied are presented and discussed. The results indicate that CIRP/PAHO/TDR initiative has contributed significantly, over the 1997–2007 period, to Chagas disease knowledge as well as to the individual and institutional-building capacity. PMID:24244761

Effects of Spaced Retrieval Training on Semantic Memory in Alzheimer's Disease: A Systematic Review

ERIC Educational Resources Information Center

Oren, Shiri; Willerton, Charlene; Small, Jeff

2014-01-01

Purpose: This article reports on a systematic review and meta-analysis of the effects of spaced retrieval training (SRT) on semantic memory in people with Alzheimer's disease (AD) or related disorder. Method: An initial systematic database search identified 454 potential studies. After screening and de-duplication, 35 studies that used SRT…

Heart Rate, Responsiveness to Intravenous Immunoglobulin, and Coronary Artery Aneurysms in Kawasaki Disease.

PubMed

Miyakoshi, Chisato; Yamamoto, Yosuke; Yamakawa, Masaru; Fukuhara, Shunichi

2018-05-21

To evaluate whether heart rate (HR) was associated with intravenous immunoglobulin (IVIG) responsiveness or development of coronary artery lesions (CALs) in patients with Kawasaki disease. We conducted a retrospective cohort study using data from in patients with Kawasaki disease who were hospitalized in our institution from 2006 to 2016. The patients were divided into 5 groups according to the age- and temperature-adjusted HR z score (HRZ age/temp ) just before IVIG administration. The ORs of outcomes were estimated by using logistic regression models, with the middle group set as the reference. Of the 322 patients, a total of 98 patients (30%) were refractory to initial IVIG treatment. The patients whose HRZ age/temp belonged to the lowest group were at the highest risk of being refractory to the initial IVIG treatment (OR 2.10 [95% CI 1.01-4.37]). Multivariable analyses showed the same trend, though this was not statistically significant. The patients with the highest HRZ age/temp were most likely to develop CALs (OR 2.61 [95%CI 0.86-7.92]). In patients with Kawasaki disease , HRs has a different relationship with IVIG responsiveness and CALs. Low HRZ age/temp might be associated with high risk of being refractory to the initial IVIG treatment, while the risk of developing CALs increased among those whose HRs were high. Further studies are necessary to investigate the mechanisms regarding HR and these outcomes in Kawasaki disease . Copyright © 2018 Elsevier Inc. All rights reserved.

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 trajectory of the disease than by a sharp decline in functional ability and, to a lesser extent, by declines in executive function.

Cognitive training in Alzheimer's disease: a controlled randomized study.

PubMed

Giovagnoli, A R; Manfredi, V; Parente, A; Schifano, L; Oliveri, S; Avanzini, G

2017-08-01

This controlled randomized single-blind study evaluated the effects of cognitive training (CT), compared to active music therapy (AMT) and neuroeducation (NE), on initiative in patients with mild to moderate Alzheimer's disease (AD). Secondarily, we explored the effects of CT on episodic memory, mood, and social relationships. Thirty-nine AD patients were randomly assigned to CT, AMT, or NE. Each treatment lasted 3 months. Before, at the end, and 3 months after treatment, neuropsychological tests and self-rated scales assessed initiative, episodic memory, depression, anxiety, and social relationships. At the end of the CT, initiative significantly improved, whereas, at the end of AMT and NE, it was unchanged. Episodic memory showed no changes at the end of CT or AMT and a worsening after NE. The rates of the patients with clinically significant improvement of initiative were greater after CT (about 62%) than after AMT (about 8%) or NE (none). At the 3-month follow-up, initiative and episodic memory declined in all patients. Mood and social relationships improved in the three groups, with greater changes after AMT or NE. In patients with mild to moderate AD, CT can improve initiative and stabilize memory, while the non-cognitive treatments can ameliorate the psychosocial aspects. The combining of CT and non-cognitive treatments may have useful clinical implications.

Ten-year outcome of enzyme replacement therapy with agalsidase beta in patients with Fabry disease.

PubMed

Germain, Dominique P; Charrow, Joel; Desnick, Robert J; Guffon, Nathalie; Kempf, Judy; Lachmann, Robin H; Lemay, Roberta; Linthorst, Gabor E; Packman, Seymour; Scott, C Ronald; Waldek, Stephen; Warnock, David G; Weinreb, Neal J; Wilcox, William R

2015-05-01

Fabry disease results from deficient α-galactosidase A activity and globotriaosylceramide accumulation causing renal insufficiency, strokes, hypertrophic cardiomyopathy and early demise. We assessed the 10-year outcome of recombinant α-galactosidase A therapy. The outcomes (severe clinical events, renal function, cardiac structure) of 52/58 patients with classic Fabry disease from the phase 3 clinical trial and extension study, and the Fabry Registry were evaluated. Disease progression rates for patients with low renal involvement (LRI, n=32) or high renal involvement (HRI, n=20) at baseline were assessed. 81% of patients (42/52) did not experience any severe clinical event during the treatment interval and 94% (49/52) were alive at the end of the study period. Ten patients reported a total of 16 events. Patients classified as LRI started therapy 13 years younger than HRI (mean 25 years vs 38 years). Mean slopes for estimated glomerular filtration rate for LRI and HRI were -1.89 mL/min/1.73 m(2)/year and -6.82 mL/min/1.73 m(2)/year, respectively. Overall, the mean left ventricular posterior wall thickness and interventricular septum thickness remained unchanged and normal. Patients who initiated treatment at age ≥ 40 years exhibited significant increase in left ventricular posterior wall thickness and interventricular septum thickness. Mean plasma globotriaosylceramide normalised within 6 months. This 10-year study documents the effectiveness of agalsidase beta (1 mg/kg/2 weeks) in patients with Fabry disease. Most patients remained alive and event-free. Patients who initiated treatment at a younger age and with less kidney involvement benefited the most from therapy. Patients who initiated treatment at older ages and/or had advanced renal disease experienced disease progression. 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.

Ten-year outcome of enzyme replacement therapy with agalsidase beta in patients with Fabry disease

PubMed Central

Germain, Dominique P; Charrow, Joel; Desnick, Robert J; Guffon, Nathalie; Kempf, Judy; Lachmann, Robin H; Lemay, Roberta; Linthorst, Gabor E; Packman, Seymour; Scott, C Ronald; Waldek, Stephen; Warnock, David G; Weinreb, Neal J; Wilcox, William R

2015-01-01

Background Fabry disease results from deficient α-galactosidase A activity and globotriaosylceramide accumulation causing renal insufficiency, strokes, hypertrophic cardiomyopathy and early demise. We assessed the 10-year outcome of recombinant α-galactosidase A therapy. Methods The outcomes (severe clinical events, renal function, cardiac structure) of 52/58 patients with classic Fabry disease from the phase 3 clinical trial and extension study, and the Fabry Registry were evaluated. Disease progression rates for patients with low renal involvement (LRI, n=32) or high renal involvement (HRI, n=20) at baseline were assessed. Results 81% of patients (42/52) did not experience any severe clinical event during the treatment interval and 94% (49/52) were alive at the end of the study period. Ten patients reported a total of 16 events. Patients classified as LRI started therapy 13 years younger than HRI (mean 25 years vs 38 years). Mean slopes for estimated glomerular filtration rate for LRI and HRI were −1.89 mL/min/1.73 m2/year and −6.82 mL/min/1.73 m2/year, respectively. Overall, the mean left ventricular posterior wall thickness and interventricular septum thickness remained unchanged and normal. Patients who initiated treatment at age ≥40 years exhibited significant increase in left ventricular posterior wall thickness and interventricular septum thickness. Mean plasma globotriaosylceramide normalised within 6 months. Conclusions This 10-year study documents the effectiveness of agalsidase beta (1 mg/kg/2 weeks) in patients with Fabry disease. Most patients remained alive and event-free. Patients who initiated treatment at a younger age and with less kidney involvement benefited the most from therapy. Patients who initiated treatment at older ages and/or had advanced renal disease experienced disease progression. PMID:25795794

Health outcomes following liver function testing in primary care: a retrospective cohort study.

PubMed

McLernon, David J; Donnan, Peter T; Ryder, Stephen; Roderick, Paul; Sullivan, Frank M; Rosenberg, William; Dillon, John F

2009-08-01

patients who present with abnormal liver function tests (LFTs) in primary care and no obvious symptoms can be difficult to manage. The objective is to follow-up a cohort of liver function tested patients to determine their outcome. This population-based retrospective cohort study was conducted in Tayside, Scotland, from 1989 to 2003. Subjects were patients with no clinically obvious liver disease at initial liver function testing in primary care. Main outcomes were diagnosed liver disease and mortality. Record linkage of databases ascertained risk factors and outcomes. Measures of performance were calculated and Weibull regression analysis from initial LFT date was performed on all outcomes by level of abnormality. In total, 95 977 patients had 364 194 incident initial LFTs, with median follow-up 3.7 years. A total of 21.7% had at least one abnormal LFT and 1108 (1.15%) developed liver disease. Elevated transaminase was strongly associated with diagnosed liver disease, hazard ratio (HR) = 4.23 (95% confidence interval 3.55, 5.04) for mild levels and HR = 12.67 (95% CI 9.74, 16.47) for severe levels versus normal. For gamma-glutamyl transferase, these hazards were 2.54 (95% CI 2.17, 2.96) and 13.44 (95% CI 10.71, 16.87), respectively. Low albumin was strongly associated with all-cause mortality, HR = 2.65 (95% CI 2.47, 2.85) for mild levels and HR = 4.99 (95% CI 4.26, 5.84) for severe levels. Sensitivity for predicting events over 5 years was low and specificity high. All LFTs were predictive markers for liver disease as well as general ill health, although sensitivity was poor. Most patients with abnormal LFTs had no later formal diagnosis of liver disease within the study period. The time taken to develop liver disease in these patients provides opportunity to intervene.

Endothelial microparticles: Pathogenic or passive players in endothelial dysfunction in autoimmune rheumatic diseases?

PubMed

McCarthy, E M; Wilkinson, F L; Parker, B; Alexander, M Y

2016-11-01

Autoimmune rheumatic diseases are characterised by systemic inflammation and complex immunopathology, with an increased risk of cardiovascular disease, initiated by endothelial dysfunction in a chronic inflammatory environment. Endothelial microparticles (EMPs) are released into the circulation from activated endothelial cells and may therefore, reflect disease severity, vascular and endothelial dysfunction, that could influence disease pathogenesis via autocrine/paracrine signalling. The exact function of EMPs in rheumatic disease remains unknown, and this has initiated research to elucidate EMP composition and function, which may be determined by the mode of endothelial activation and the micro environment. To date, EMPs are thought to play a role in angiogenesis, thrombosis and inflammation by transferring specific proteins and microRNAs (miRs) to target cells. Here, we review the mechanisms underlying the generation and composition of EMPs and the clinical and experimental studies describing the involvement of EMPs in rheumatic diseases, since we have previously shown endothelial dysfunction and an elevated risk of cardiovascular disease are characteristics in systemic lupus erythematosus. We will also discuss the potential of EMPs as future biomarkers of cardiovascular risk in these diseases. Copyright © 2016 Elsevier Inc. All rights reserved.

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

Listeriosis Outbreaks and Associated Food Vehicles, United States, 1998–2008

PubMed Central

Cartwright, Emily J.; Jackson, Kelly A.; Johnson, Shacara D.; Graves, Lewis M.; Mahon, Barbara E.

2013-01-01

Listeria monocytogenes, a bacterial foodborne pathogen, can cause meningitis, bacteremia, and complications during pregnancy. This report summarizes listeriosis outbreaks reported to the Foodborne Disease Outbreak Surveillance System of the Centers for Disease Control and Prevention during 1998–2008. The study period includes the advent of PulseNet (a national molecular subtyping network for outbreak detection) in 1998 and the Listeria Initiative (enhanced surveillance for outbreak investigation) in 2004. Twenty-four confirmed listeriosis outbreaks were reported during 1998–2008, resulting in 359 illnesses, 215 hospitalizations, and 38 deaths. Outbreaks earlier in the study period were generally larger and longer. Serotype 4b caused the largest number of outbreaks and outbreak-associated cases. Ready-to-eat meats caused more early outbreaks, and novel vehicles (i.e., sprouts, taco/nacho salad) were associated with outbreaks later in the study period. These changes may reflect the effect of PulseNet and the Listeria Initiative and regulatory initiatives designed to prevent contamination in ready-to-eat meat and poultry products. PMID:23260661

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.

Barriers to preemptive renal transplantation: a single center questionnaire study.

PubMed

Knight, Richard J; Teeter, Larry D; Graviss, Edward A; Patel, Samir J; DeVos, Jennifer M; Moore, Linda W; Gaber, A Osama

2015-03-01

Preemptive transplantation results in excellent patient and graft survival yet most transplant candidates are referred for transplantation after initiation of dialysis. The goal of this study was to determine barriers to preemptive renal transplantation. A nonvalidated questionnaire was administered to prospective kidney transplant recipients to determine factors that hindered or favored referral for transplantation before the initiation of dialysis. One hundred ninety-seven subjects referred for a primary renal transplant completed the questionnaire. Ninety-one subjects (46%) had been informed of preemptive transplantation before referral, and 80 (41%) were predialysis at the time of evaluation. The median time from diagnosis of renal disease to referral was 60 months (range, 2-444 months). In bivariate analysis, among other factors, knowledge of preemptive transplantation was highly associated (odds ratio=94.69) with referral before initiation of dialysis. Given the strong association between knowledge of preemptive transplantation and predialysis referral, this variable was not included in the multivariate analysis. Using multivariate logistic regression analysis, white recipient race, referral by a transplant nephrologist, recipient employment, and the diagnosis of polycystic kidney disease were significantly associated with presentation to the pretransplant clinic before initiation of dialysis. The principle barrier to renal transplantation referral before dialysis was patient education regarding the option of preemptive transplantation. Factors significantly associated with referral before dialysis were the diagnosis of polycystic kidney disease, white recipient race, referral by a transplant nephrologist, and employed status. Greater effort should be applied to patient education regarding preemptive transplantation early after the diagnosis of end-stage renal disease.

Chest wall recurrence after mastectomy does not always portend a dismal outcome.

PubMed

Chagpar, Anees; Meric-Bernstam, Funda; Hunt, Kelly K; Ross, Merrick I; Cristofanilli, Massimo; Singletary, S Eva; Buchholz, Thomas A; Ames, Frederick C; Marcy, Sylvie; Babiera, Gildy V; Feig, Barry W; Hortobagyi, Gabriel N; Kuerer, Henry M

2003-07-01

Chest wall recurrence (CWR) after mastectomy often forecasts a grim prognosis. Predictors of outcome after CWR, however, are not clear. From 1988 to 1998, 130 patients with isolated CWRs were seen at our center. Clinicopathologic factors were studied by univariate and multivariate analyses for distant metastasis-free survival after CWR. The median post-CWR follow-up was 37 months. Initial nodal status was the strongest predictor of outcome by univariate analysis. Other significant factors included initial T4 disease, primary lymphovascular invasion, treatment of the primary tumor with neoadjuvant therapy or radiation, time to CWR >24 months, and treatment for CWR (surgery, radiation, or multimodality therapy). Multivariate analysis also found initial nodal status to have the greatest effect; time to CWR and use of radiation for CWR were also independent predictors. Three groups of patients were identified. Low risk was defined by initial node-negative disease, time to CWR >24 months, and radiation for CWR; intermediate risk had one or two favorable features; and high risk had none. The median distant metastasis-free survival after CWR was significantly different among these groups (P <.0001). Patients with CWR are a heterogeneous population. Patients with initial node-negative disease who develop CWR after 24 months have an optimistic prognosis, especially if they are treated with radiation.

Effect of Discontinuation or Initiation of Methotrexate or Glucocorticoids on Tofacitinib Efficacy in Patients with Rheumatoid Arthritis: A Post Hoc Analysis.

PubMed

Fleischmann, Roy; Wollenhaupt, Jürgen; Cohen, Stanley; Wang, Lisy; Fan, Haiyun; Bandi, Vara; Andrews, John; Takiya, Liza; Bananis, Eustratios; Weinblatt, Michael E

2018-06-01

Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). We evaluated the effect of concomitant methotrexate (MTX) or glucocorticoid (GC) use on tofacitinib clinical efficacy. Data were pooled from two open-label, long-term extension studies of tofacitinib 5 or 10 mg twice daily in patients with RA. Response according to Clinical Disease Activity Index (CDAI) was assessed separately in patients who discontinued (no MTX/GC use within 30 days prior to year-3 visit; assessment at month 3/year 3) or initiated (on/before year 3; assessment at initiation and year 3) MTX/GC. By year 3, among patients receiving background MTX at baseline, 186/1608 (11.6%) discontinued MTX, and 319/1434 (22.2%) patients receiving GC at baseline discontinued GC. Overall, 70.4/69.1% of patients who discontinued/continued MTX and 72.7/65.9% who discontinued/continued GC achieved CDAI remission or low disease activity (LDA) at year 3. Month 3 remission/LDA rates were maintained at year 3 in the majority of patients, irrespective of MTX/GC discontinuation/continuation. By year 3, 6.2% of patients receiving tofacitinib without MTX at baseline had initiated concomitant MTX, and 25.1% receiving tofacitinib without GC initiated GC; 69.0% and 45.4% initiating MTX or GC, respectively, had a CDAI-defined incomplete response prior to initiation. RA signs/symptoms improved following MTX initiation; only modest improvement was observed with GC initiation. Patients achieving remission/LDA with tofacitinib may discontinue MTX or GC and maintain treatment response. Patients with an incomplete response may benefit from adding concomitant MTX. Pfizer Inc. Study A3921024 [NCT00413699] and Study A3921041 [NCT00661661].

Therapy-induced selective loss of leukemia-initiating activity in murine adult T cell leukemia

PubMed Central

El Hajj, Hiba; El-Sabban, Marwan; Hasegawa, Hideki; Zaatari, Ghazi; Ablain, Julien; Saab, Shahrazad T.; Janin, Anne; Mahfouz, Rami; Nasr, Rihab; Kfoury, Youmna; Nicot, Christophe; Hermine, Olivier; Hall, William

2010-01-01

Chronic HTLV-I (human T cell lymphotropic virus type I) infection may cause adult T cell leukemia/lymphoma (ATL), a disease with dismal long-term prognosis. The HTLV-I transactivator, Tax, initiates ATL in transgenic mice. In this study, we demonstrate that an As2O3 and IFN-α combination, known to trigger Tax proteolysis, cures Tax-driven ATL in mice. Unexpectedly, this combination therapy abrogated initial leukemia engraftment into secondary recipients, whereas the primary tumor bulk still grew in the primary hosts, only to ultimately abate later on. This loss of initial transplantability required proteasome function. A similar regimen recently yielded unprecedented disease control in human ATL. Our demonstration that this drug combination targeting Tax stability abrogates tumor cell immortality but not short-term growth may foretell a favorable long-term efficiency of this regimen in patients. PMID:21135137

Bacterial meningitis.

PubMed

Heckenberg, Sebastiaan G B; Brouwer, Matthijs C; van de Beek, Diederik

2014-01-01

Bacterial meningitis is a neurologic emergency. Vaccination against common pathogens has decreased the burden of disease. Early diagnosis and rapid initiation of empiric antimicrobial and adjunctive therapy are vital. Therapy should be initiated as soon as blood cultures have been obtained, preceding any imaging studies. Clinical signs suggestive of bacterial meningitis include fever, headache, meningismus, and an altered level of consciousness but signs may be scarce in children, in the elderly, and in meningococcal disease. Host genetic factors are major determinants of susceptibility to meningococcal and pneumococcal disease. Dexamethasone therapy has been implemented as adjunctive treatment of adults with pneumococcal meningitis. Adequate and prompt treatment of bacterial meningitis is critical to outcome. In this chapter we review the epidemiology, pathophysiology, and management of bacterial meningitis. © 2014 Elsevier B.V. All rights reserved.

Understanding age-based transition needs: Perspectives from adolescents and adults with congenital heart disease

USDA-ARS?s Scientific Manuscript database

The purpose of this study was to explore the transition process in congenital heart disease (CHD) care through the perceived needs and concerns of adolescents (pretransition) and the experiential insight from adults (post-transition), in order to inform future transition initiatives and information ...

The use of simple indicators for detecting potential coronary heart disease susceptibility in the third-class airman population.

DOT National Transportation Integrated Search

1972-07-01

An analysis was made of an eight-year interval change in several Framingham Heart Study (FHS) indicators of coronary heart disease (CHD) susceptibility as measured on 475 male air traffic control (ATC) personnel. The initial measurements were obtaine...

Hip1 and Hippi participate in a novel cell death-signaling pathway.

PubMed

Wanker, Erich E

2002-02-01

Neuronal apoptosis is a cardinal feature of late-onset neurodegenerative disorders such as Alzheimer's and Huntington's disease. Biochemical and cell biological studies point to a role for Hip1 and Hippi in caspase-8 activation and the initiation of apoptosis during the pathogenesis of Huntington's disease.

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.

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

Implications of DRG Classification in a Bundled Payment Initiative for COPD

PubMed Central

PAREKH, TRISHA M.; BHATT, SURYA P.; WESTFALL, ANDREW O.; WELLS, JAMES M.; KIRKPATRICK, DENAY; IYER, ANAND S.; MUGAVERO, MICHAEL; WILLIG, JAMES H.; DRANSFIELD, MARK T.

2018-01-01

OBJECTIVES Institutions participating in the Medicare Bundled Payments for Care Improvement (BPCI) initiative invest significantly in efforts to reduce readmissions and costs for patients who are included in the program. Eligibility for the BPCI initiative is determined by diagnosis-related group (DRG) classification. The implications of this methodology for chronic diseases are not known. We hypothesized that patients included in a BPCI initiative for chronic obstructive pulmonary disease (COPD) would have less severe illness and decreased hospital utilization compared with those excluded from the bundled payment initiative. STUDY DESIGN Retrospective observational study. METHODS We sought to determine the clinical characteristics and outcomes of Medicare patients admitted to the University of Alabama at Birmingham Hospital with acute exacerbations of COPD between 2012 and 2014 who were included and excluded in a BPCI initiative. Patients were included in the analysis if they were discharged with a COPD DRG or with a non-COPD DRG but with an International Classification of Diseases, Ninth Revision code for COPD exacerbation. RESULTS Six hundred and ninety-eight unique patients were discharged for an acute exacerbation of COPD; 239 (34.2%) were not classified into a COPD DRG and thus were excluded from the BPCI initiative. These patients were more likely to have intensive care unit (ICU) admissions (63.2% vs 4.4%, respectively; P <.001) and require noninvasive (46.9% vs 6.5%; P <.001) and invasive mechanical ventilation (41.4% vs 0.7%; P <.001) during their hospitalization than those in the initiative. They also had a longer ICU length of stay (5.2 vs 1.8 days; P = .011), longer hospital length of stay (10.3 days vs 3.9 days; P <.001), higher in-hospital mortality (14.6% vs 0.7%; P <.001), and greater hospitalization costs (median = $13,677 [interquartile range = $7489-$23,054] vs $4281 [$2718-$6537]; P <.001). CONCLUSIONS The use of DRGs to identify patients with COPD for inclusion in the BPCI initiative led to the exclusion of more than one-third of patients with acute exacerbations who had more severe illness and worse outcomes and who may benefit most from the additional interventions provided by the initiative. PMID:29623307

Persistence of thyrotropin (TSH) receptor antibodies in children and adolescents with Graves' disease treated using antithyroid medication.

PubMed

Smith, Jessica; Brown, Rosalind S

2007-11-01

To determine the course of thyrotropin (thyroid-stimulating hormone [TSH]) receptor antibodies (TRAbs) in children and adolescents with Graves' disease treated using antithyroid drugs (ATDs). Retrospective, cross-sectional study of 86 children and adolescents with Graves' disease treated medically for >3 years. Patients with Hashimoto's thyroiditis and idiopathic short stature (n = 30) served as controls. A second-generation enzyme-linked immunosorbent assay (ELISA) for TRAbs was used. Twenty-two out of 23 (95.7%) patients with newly diagnosed Graves' disease, but 0/30 controls, had detectable TRAbs (22.0 +/- 13.5 U/L [mean +/- SD] vs. 0.9 +/- 0.9 U/L, p < 0.0001). Mean TRAb levels decreased with duration of therapy, but even after 13-24 months, TRAbs had normalized in only 3/16 (18.8%) patients. The initial TRAb titer correlated significantly with severity of the initial hyperthyroidism, but did not predict the response to therapy as indicated by the dosage of ATD required to control the hyperthyroidism at 6 and 12 months. Unlike adults, most children and adolescents with Graves' disease require >2 years of ATD treatment before TRAbs are normalized. Although initial TRAb activity reflects disease severity, it does not predict the response to medical therapy. Recommendations as to treatment duration developed for adult patients should not be applied to the young.

Hemodialysis versus Peritoneal Dialysis: A Comparison of Survival Outcomes in South-East Asian Patients with End-Stage Renal Disease.

PubMed

Yang, Fan; Khin, Lay-Wai; Lau, Titus; Chua, Horng-Ruey; Vathsala, A; Lee, Evan; Luo, Nan

2015-01-01

Studies comparing patient survival of hemodialysis (HD) and peritoneal dialysis (PD) have yielded conflicting results and no such study was from South-East Asia. This study aimed to compare the survival outcomes of patients with end-stage renal disease (ESRD) who started dialysis with HD and PD in Singapore. Survival data for a maximum of 5 years from a single-center cohort of 871 ESRD patients starting dialysis with HD (n = 641) or PD (n = 230) from 2005-2010 was analyzed using the flexible Royston-Parmar (RP) model. The model was also applied to a subsample of 225 propensity-score-matched patient pairs and subgroups defined by age, diabetes mellitus, and cardiovascular disease. After adjusting for the effect of socio-demographic and clinical characteristics, the risk of death was higher in patients initiating dialysis with PD than those initiating dialysis with HD (hazard ratio [HR]: 2.08; 95% confidence interval [CI]: 1.67-2.59; p<0.001), although there was no significant difference in mortality between the two modalities in the first 12 months of treatment. Consistently, in the matched subsample, patients starting PD had a higher risk of death than those starting HD (HR: 1.73, 95% CI: 1.30-2.28, p<0.001). Subgroup analysis showed that PD may be similar to or better than HD in survival outcomes among young patients (≤65 years old) without diabetes or cardiovascular disease. ESRD patients who initiated dialysis with HD experienced better survival outcomes than those who initiated dialysis with PD in Singapore, although survival outcomes may not differ between the two dialysis modalities in young and healthier patients. These findings are potentially confounded by selection bias, as patients were not randomized to the two dialysis modalities in this cohort study.

Recent Progress in the Diagnosis and Treatment of Ovarian Cancer

PubMed Central

Jelovac, Danijela; Armstrong, Deborah K.

2013-01-01

Epithelial ovarian cancer is the most lethal of the gynecologic malignancies, largely due to the advanced stage at diagnosis in most patients. Screening strategies using ultrasound and the cancer antigen (CA) 125 tumor marker are currently under study and may lower stage at diagnosis but have not yet been shown to improve survival. Women who have inherited a deleterious mutation in the BRCA1 or BRCA2 gene and those with the Lynch syndrome (hereditary nonpolyposis colorectal cancer) have the highest risk of developing ovarian cancer but account for only approximately 10% of those with the disease. Other less common and less well-defined genetic syndromes may increase the risk of ovarian cancer, but their contribution to genetic risk is small. A clear etiology for sporadic ovarian cancer has not been identified, but risk is affected by reproductive and hormonal factors. Surgery has a unique role in ovarian cancer, as it is used not only for diagnosis and staging but also therapeutically, even in patients with widely disseminated, advanced disease. Ovarian cancer is highly sensitive to chemotherapy drugs, particularly the platinum agents, and most patients will attain a remission with initial treatment. Recent advances in the delivery of chemotherapy using the intraperitoneal route have further improved survival after initial therapy. Although the majority of ovarian cancer patients will respond to initial chemotherapy, most will ultimately develop disease recurrence. Chemotherapy for recurrent disease includes platinum-based, multiagent regimens for women whose disease recurs more than 6 to 12 months after the completion of initial therapy and sequential single agents for those whose disease recurs earlier. New targeted biologic agents, particularly those involved with the vascular endothelial growth factor pathway and those targeting the poly (ADP-ribose) polymerase (PARP) enzyme, hold great promise for improving the outcome of ovarian cancer. PMID:21521830

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.

Reversible lesions in the brain parenchyma in Wilson's disease confirmed by magnetic resonance imaging: earlier administration of chelating therapy can reduce the damage to the brain.

PubMed

Kozić, Duško B; Petrović, Igor; Svetel, Marina; Pekmezović, Tatjana; Ragaji, Aleksandar; Kostić, Vladimir S

2014-11-01

The aim of this study was to evaluate the resolution of brain lesions in patients with Wilson's disease during the long-term chelating therapy using magnetic resonance imaging and a possible significance of the time latency between the initial symptoms of the disease and the introduction of this therapy. Initial magnetic resonance examination was performed in 37 patients with proven neurological form of Wilson's disease with cerebellar, parkinsonian and dystonic presentation. Magnetic resonance reexamination was done 5.7 ± 1.3 years later in 14 patients. Patients were divided into: group A, where chelating therapy was initiated < 24 months from the first symptoms and group B, where the therapy started ≥ 24 months after the initial symptoms. Symmetry of the lesions was seen in 100% of patients. There was a significant difference between groups A and B regarding complete resolution of brain stem and putaminal lesions (P = 0.005 and P = 0.024, respectively). If the correct diagnosis and adequate treatment are not established less than 24 months after onset of the symptoms, irreversible lesions in the brain parenchyma could be expected. Signal abnormalities on magnetic resonance imaging might therefore, at least in the early stages, represent reversible myelinolisis or cytotoxic edema associated with copper toxicity.

Detecting lower extremity vascular dynamics in patients with peripheral artery disease using diffuse optical tomography

NASA Astrophysics Data System (ADS)

Khalil, Michael A.; Kim, Hyun-Keol K.; Kim, In-Kyong; Dayal, Rajeev; Hielscher, Andreas H.

2011-02-01

Peripheral Artery Disease (PAD) affects over 10 million Americans and is associated with significant morbidity and mortality. While in many cases the ankle-brachial index (ABI) can be used for diagnosing the disease, this parameter is not dependable in the diabetic and elderly population. These populations tend to have calcified arteries, which leads to elevated ABI values. Dynamic optical tomography (DDOT) promises to overcome the limitations of the current diagnostic techniques and has the potential to initiate a paradigm shift in the diagnosis of vascular disease. We have performed initial pilot studies involving 5 PAD patients and 3 healthy volunteers. The time traces and tomographic reconstruction obtained from measurements on the feet show significant differences between healthy and affected vasculatures. In addition, we found that DOT is capable of identifying PAD in diabetic patients, who are misdiagnosed by the traditional ABI screening.

Physics of Cell Adhesion Failure and Human Diseases

NASA Astrophysics Data System (ADS)

Family, Fereydoon

Emergent phenomena in living systems, including your ability to read these lines, do not obviously follow as a consequence of the fundamental laws of physics. Understanding the physics of living systems clearly falls outside the conventional boundaries of scientific disciplines and requires a collaborative, multidisciplinary approach. Here I will discuss how theoretical and computational techniques from statistical physics can be used to make progress in explaining the physical mechanisms that underlie complex biological phenomena, including major diseases. In the specific cases of macular degeneration and cancer that we have studied recently, we find that the breakdown of the mechanical stability in the local tissue structure caused by weakening of the cell-cell adhesion plays a key role in the initiation and progression of the disease. This finding can help in the development of new therapies that would prevent or halt the initiation and progression of these diseases.

[Personal genome research and neurological diseases: overview].

PubMed

Toda, Tatsushi

2013-03-01

Neurological diseases include those caused by a single defective gene,e.g., Huntington's disease, other polyglutamine diseases, and muscular dystrophies, and those that are mostly sporadic but rarely show Mendelian inheritance in some families, e.g., Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and epilepsy. The latter diseases are considered polygenic disorders. Both sporadic and Mendelian cases of these diseases are believed to share some common pathological mechanisms. Since the detection of causal genes for the Mendelian cases, studies have been initiated on disease pathology. SNPs and rare gene variants play important roles in common neurological diseases. From a technological perspective, next-generation sequencers have become widely available and have contributed to the advancement of research based on individual genome sequences (personal genome). This paper presents an overview, as well as a historical context, of the contribution of personal genome research to neurological disease studies.

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

[Long-term prognostic factors in Parkinson's disease (author's transl)].

PubMed

Guillard, A; Chastang, C

1978-05-01

Acturial methods are used to study the correlation between the initial condition and early therapeutic results, and the present condition of 164 parkinsonian patients treated with L. dopa for 4 to 8 years. There is an ineluctable deterioration in motility. There is a lower risk in patients who are autonomous and only slightly akinetic at the beginning of treatment. Intellectual deterioration is seen in some patients only. The risk factors are: males, the clinical forms of Parkinson's disease in which tremor is not predominant, onset of the disease before 60 years of age, and depression and transitory psychotic disorders during the first year of treatment. This deterioration appears 3 to 5 years after starting dopatherapy, which could be the cause. Life expectancy is still reduced by the disease at the present time. It is longer in patients in whom the disease started with isolated tremors, absence of Babinski's sign, and no loss of autonomy, and those in whom a good initial therapeutic result was obtained.

Effect of 24-h continuous rotigotine treatment on stationary and non-stationary locomotion in de novo patients with Parkinson disease in an open-label uncontrolled study.

PubMed

Serrao, Mariano; Ranavolo, Alberto; Conte, Carmela; Davassi, Chiara; Mari, Silvia; Fasano, Alfonso; Chini, Giorgia; Coppola, Gianluca; Draicchio, Francesco; Pierelli, Francesco

2015-11-01

The aim of this study was to investigate the effect of a rotigotine transdermal patch on stationary and non-stationary locomotion in de novo Parkinson disease (PD) patients in an open-label uncontrolled study. A 3-D gait analysis system was used to investigate four different locomotor tasks: steady-state linear walking, gait initiation, gait termination and 180°-turning. A series of gait variables were measured for each locomotor task. PD patients who received rotigotine treatment (4-8 mg) displayed: (1) increased step length, gait speed, cadence and arm oscillations, and reduced double support duration and step asymmetry during steady-state linear gait; (2) increased initial step length during gait initiation; (3) increased final step length and gait speed, and decreased stability index during gait termination; (4) decreased duration of turning and head-pelvis delays during 180°-turning. The main finding that emerges from the present study is that the dopamine agonist rotigotine can improve various aspects of gait in de novo PD patients.

Bee Venom for the Treatment of Parkinson Disease - A Randomized Controlled Clinical Trial.

PubMed

Hartmann, Andreas; Müllner, Julia; Meier, Niklaus; Hesekamp, Helke; van Meerbeeck, Priscilla; Habert, Marie-Odile; Kas, Aurélie; Tanguy, Marie-Laure; Mazmanian, Merry; Oya, Hervé; Abuaf, Nissen; Gaouar, Hafida; Salhi, Sabrina; Charbonnier-Beaupel, Fanny; Fievet, Marie-Hélène; Galanaud, Damien; Arguillere, Sophie; Roze, Emmanuel; Degos, Bertrand; Grabli, David; Lacomblez, Lucette; Hubsch, Cécile; Vidailhet, Marie; Bonnet, Anne-Marie; Corvol, Jean-Christophe; Schüpbach, Michael

2016-01-01

In the present study, we examined the potential symptomatic and/or disease-modifying effects of monthly bee venom injections compared to placebo in moderatly affected Parkinson disease patients. We conducted a prospective, randomized double-blind study in 40 Parkinson disease patients at Hoehn & Yahr stages 1.5 to 3 who were either assigned to monthly bee venom injections or equivalent volumes of saline (treatment/placebo group: n = 20/20). The primary objective of this study was to assess a potential symptomatic effect of s.c. bee venom injections (100 μg) compared to placebo 11 months after initiation of therapy on United Parkinson’s Disease Rating Scale (UPDRS) III scores in the « off » condition pre-and post-injection at a 60 minute interval. Secondary objectives included the evolution of UPDRS III scores over the study period and [123I]-FP-CIT scans to evaluate disease progression. Finally, safety was assessed by monitoring specific IgE against bee venom and skin tests when necessary. After an 11 month period of monthly administration, bee venom did not significantly decrease UPDRS III scores in the « off » condition. Also, UPDRS III scores over the study course, and nuclear imaging, did not differ significantly between treatment groups. Four patients were excluded during the trial due to positive skin tests but no systemic allergic reaction was recorded. After an initial increase, specific IgE against bee venom decreased in all patients completing the trial. This study did not evidence any clear symptomatic or disease-modifying effects of monthly bee venom injections over an 11 month period compared to placebo using a standard bee venom allergy desensitization protocol in Parkinson disease patients. However, bee venom administration appeared safe in non-allergic subjects. Thus, we suggest that higher administration frequency and possibly higher individual doses of bee venom may reveal its potency in treating Parkinson disease. ClinicalTrials.gov NCT01341431.

Bee Venom for the Treatment of Parkinson Disease – A Randomized Controlled Clinical Trial

PubMed Central

Hartmann, Andreas; Müllner, Julia; Meier, Niklaus; Hesekamp, Helke; van Meerbeeck, Priscilla; Habert, Marie-Odile; Kas, Aurélie; Tanguy, Marie-Laure; Mazmanian, Merry; Oya, Hervé; Abuaf, Nissen; Gaouar, Hafida; Salhi, Sabrina; Charbonnier-Beaupel, Fanny; Fievet, Marie-Hélène; Galanaud, Damien; Arguillere, Sophie; Roze, Emmanuel; Degos, Bertrand; Grabli, David; Lacomblez, Lucette; Hubsch, Cécile; Vidailhet, Marie; Bonnet, Anne-Marie

2016-01-01

In the present study, we examined the potential symptomatic and/or disease-modifying effects of monthly bee venom injections compared to placebo in moderatly affected Parkinson disease patients. We conducted a prospective, randomized double-blind study in 40 Parkinson disease patients at Hoehn & Yahr stages 1.5 to 3 who were either assigned to monthly bee venom injections or equivalent volumes of saline (treatment/placebo group: n = 20/20). The primary objective of this study was to assess a potential symptomatic effect of s.c. bee venom injections (100 μg) compared to placebo 11 months after initiation of therapy on United Parkinson’s Disease Rating Scale (UPDRS) III scores in the « off » condition pre-and post-injection at a 60 minute interval. Secondary objectives included the evolution of UPDRS III scores over the study period and [123I]-FP-CIT scans to evaluate disease progression. Finally, safety was assessed by monitoring specific IgE against bee venom and skin tests when necessary. After an 11 month period of monthly administration, bee venom did not significantly decrease UPDRS III scores in the « off » condition. Also, UPDRS III scores over the study course, and nuclear imaging, did not differ significantly between treatment groups. Four patients were excluded during the trial due to positive skin tests but no systemic allergic reaction was recorded. After an initial increase, specific IgE against bee venom decreased in all patients completing the trial. This study did not evidence any clear symptomatic or disease-modifying effects of monthly bee venom injections over an 11 month period compared to placebo using a standard bee venom allergy desensitization protocol in Parkinson disease patients. However, bee venom administration appeared safe in non-allergic subjects. Thus, we suggest that higher administration frequency and possibly higher individual doses of bee venom may reveal its potency in treating Parkinson disease. Trial Registration ClinicalTrials.gov NCT01341431 PMID:27403743

An environmental scan of policies in support of chronic disease self-management in Canada.

PubMed

Liddy, C; Mill, K

2014-02-01

The evidence supporting chronic disease self-management warrants further attention. Our aim was to identify existing policies, strategies and frameworks that support self-management initiatives. This descriptive study was conducted as an environmental scan, consisting of an Internet search of government and other publicly available websites, and interviews with jurisdictional representatives identified through the Health Council of Canada and academic networking. We interviewed 16 representatives from all provinces and territories in Canada and found 30 publicly available and relevant provincial and national documents. Most provinces and territories have policies that incorporate aspects of chronic disease self-management. Alberta and British Columbia have the most detailed policies. Both feature primary care prominently and are not disease specific. Both also have provincial level implementation of chronic disease self-management programming. Canada's northern territories all lacked specific policies supporting chronic disease self-management despite a significant burden of disease. Engaging patients in self-management of their chronic diseases is important and effective. Although most provinces and territories have policies that incorporate aspects of chronic disease self-management, they were often embedded within other initiatives and/or policy documents framed around specific diseases or populations. This approach could limit the potential reach and effect of self-management.

Comparison of primary and reoperative surgery in patients with Crohns disease.

PubMed Central

Heimann, T M; Greenstein, A J; Lewis, B; Kaufman, D; Heimann, D M; Aufses, A H

1998-01-01

OBJECTIVE: This study was performed to determine the clinical results of patients with Crohns disease who require surgical resection. The outcome of patients undergoing initial surgery was compared with those having reoperation. METHODS: One hundred sixty-four patients undergoing intestinal resection for Crohns disease at The Mount Sinai Hospital from 1976 to 1989 were studied prospectively. The mean duration of follow-up was 72 months. RESULTS: Ninety patients (55%) underwent initial intestinal resection whereas 74 patients (45%) underwent reoperation for recurrent disease. Patients undergoing reoperation were older (33.4 vs. 38.7 years), had longer durations of disease (8.7 vs. 15.2 years), had shorter resections (60 vs. 46 cm), and were more likely to require ileostomy. Forty-seven percent of the patients with multiple previous resections required an ileostomy. This group also received a mean of 2.3 U blood in the perioperative period and showed a trend to increased symptomatic recurrence (49% vs. 71% at 5 years). CONCLUSIONS: Patients with Crohns disease undergoing first and second reoperation have outcomes similar to those in patients undergoing primary resection. Patients requiring multiple reoperations are more likely to require blood transfusions and permanent ileostomy and to show a greater trend to early symptomatic recurrence. PMID:9563535

Statistical physics of medical diagnostics: Study of a probabilistic model.

PubMed

Mashaghi, Alireza; Ramezanpour, Abolfazl

2018-03-01

We study a diagnostic strategy which is based on the anticipation of the diagnostic process by simulation of the dynamical process starting from the initial findings. We show that such a strategy could result in more accurate diagnoses compared to a strategy that is solely based on the direct implications of the initial observations. We demonstrate this by employing the mean-field approximation of statistical physics to compute the posterior disease probabilities for a given subset of observed signs (symptoms) in a probabilistic model of signs and diseases. A Monte Carlo optimization algorithm is then used to maximize an objective function of the sequence of observations, which favors the more decisive observations resulting in more polarized disease probabilities. We see how the observed signs change the nature of the macroscopic (Gibbs) states of the sign and disease probability distributions. The structure of these macroscopic states in the configuration space of the variables affects the quality of any approximate inference algorithm (so the diagnostic performance) which tries to estimate the sign-disease marginal probabilities. In particular, we find that the simulation (or extrapolation) of the diagnostic process is helpful when the disease landscape is not trivial and the system undergoes a phase transition to an ordered phase.

Statistical physics of medical diagnostics: Study of a probabilistic model

NASA Astrophysics Data System (ADS)

Mashaghi, Alireza; Ramezanpour, Abolfazl

2018-03-01

We study a diagnostic strategy which is based on the anticipation of the diagnostic process by simulation of the dynamical process starting from the initial findings. We show that such a strategy could result in more accurate diagnoses compared to a strategy that is solely based on the direct implications of the initial observations. We demonstrate this by employing the mean-field approximation of statistical physics to compute the posterior disease probabilities for a given subset of observed signs (symptoms) in a probabilistic model of signs and diseases. A Monte Carlo optimization algorithm is then used to maximize an objective function of the sequence of observations, which favors the more decisive observations resulting in more polarized disease probabilities. We see how the observed signs change the nature of the macroscopic (Gibbs) states of the sign and disease probability distributions. The structure of these macroscopic states in the configuration space of the variables affects the quality of any approximate inference algorithm (so the diagnostic performance) which tries to estimate the sign-disease marginal probabilities. In particular, we find that the simulation (or extrapolation) of the diagnostic process is helpful when the disease landscape is not trivial and the system undergoes a phase transition to an ordered phase.

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.

Establishing a Consortium for the Study of Rare Diseases: The Urea Cycle Disorders Consortium

PubMed Central

Seminara, Jennifer; Tuchman, Mendel; Krivitzky, Lauren; Krischer, Jeffrey; Lee, Hye-Seung; LeMons, Cynthia; Baumgartner, Matthias; Cederbaum, Stephen; Diaz, George A.; Feigenbaum, Annette; Gallagher, Renata C.; Harding, Cary O.; Kerr, Douglas S.; Lanpher, Brendan; Lee, Brendan; Lichter-Konecki, Uta; McCandless, Shawn E.; Merritt, J. Lawrence; Oster-Granite, Mary Lou; Seashore, Margretta R.; Stricker, Tamar; Summar, Marshall; Waisbren, Susan; Yudkoff, Marc; Batshaw, Mark L.

2010-01-01

The Urea Cycle Disorders Consortium (UCDC) was created as part of a larger network established by the National Institutes of Health to study rare diseases. This paper reviews the UCDC’s accomplishments over the first six years, including how the Consortium was developed and organized, clinical research studies initiated, and the importance of creating partnerships with patient advocacy groups, philanthropic foundations and biotech and pharmaceutical companies. PMID:20188616

Early initiation of night-time NIV in an outpatient setting: a randomized non-inferiority study in ALS patients.

PubMed

Bertella, Enrica; Banfi, Paolo; Paneroni, Mara; Grilli, Silvia; Bianchi, Luca; Volpato, Eleonora; Vitacca, Michele

2017-12-01

In patients with amyotrophic lateral sclerosis (ALS), non-invasive ventilation (NIV) is usually initiated in an in-hospital regime. We investigated if NIV initiated in an outpatient setting can be as effective in terms of patients' acceptance/adherence. We also evaluated factors predicting NIV acceptance and adherence and disease progression. Prospective randomized study. Outpatient versus inpatient rehabilitation. ALS patients. ALS patients were randomized to two groups for NIV initiation: outpatients versus inpatients. At baseline (T0), end of NIV trial program (T1) and after 3 months from T1 (T2), respiratory function tests, blood gas analysis, and sleep study were performed. At T1, we assessed: NIV acceptance (>4 h/night), and dyspnea symptoms (day/night) by Visual analogue scale (VAS), staff and patients' experience (how difficult NIV was to accept, how difficult ventilator was to manage, satisfaction); at T2: NIV adherence (>120 h/month) and patients' experience. Fifty patients participated. There were no differences in acceptance failure (P=0.733) or adherence failure (P=0.529). At T1, outpatients had longer hours of nocturnal ventilation (P<0.02), at T2 this was similar (P=0.34). Female gender and spinal onset of the disease were predictors for NIV acceptance/adherence failure. There were no between-group differences in progression of respiratory impairment, symptoms and sleep quality. Early outpatient initiation of NIV in ALS is as effective as inpatient initiation.

Pituitary gigantism: a retrospective case series.

PubMed

Creo, Ana L; Lteif, Aida N

2016-05-01

Pituitary gigantism (PG) is a rare pediatric disease with poorly defined long-term outcomes. Our aim is to describe the longitudinal clinical course in PG patients using a single-center, retrospective cohort study. Patients younger than 19 years diagnosed with PG were identified. Thirteen cases were confirmed based on histopathology of a GH secreting adenoma or hyperplasia and a height >2 SD for age and gender. Laboratory studies, initial pathology, and imaging were abstracted. Average age at diagnosis was 13 years with an average initial tumor size of 7.4×3.8 mm. Initial transsphenoidal surgery was curative in 3/12 patients. Four of the nine patients who failed the initial surgery required a repeat procedure. Octreotide successfully normalized GH levels in 1/6 patients with disease refractory to surgery (1/6). Two out of five patients received pegvisomant after failing octreotide but only one patient responded to treatment. Five patients were ultimately treated with radiosurgery or radiation patients were followed for an average of 10 years. PG is difficult to treat. In most patients, the initial transsphenoidal surgery failed to normalize GH levels. If the initial surgery was unsuccessful, repeat surgery was unlikely to control GH secretion. Treatment with octreotide or pegvisomant was successful in less than half the patients failing surgery. Radiosurgery was curative, but is not an optimal treatment for pediatric patients. Despite the small sample, our study suggests that the treatment outcome of pediatric PG may be different than adults.

Optimizing surveillance for livestock disease spreading through animal movements

PubMed Central

Bajardi, Paolo; Barrat, Alain; Savini, Lara; Colizza, Vittoria

2012-01-01

The spatial propagation of many livestock infectious diseases critically depends on the animal movements among premises; so the knowledge of movement data may help us to detect, manage and control an outbreak. The identification of robust spreading features of the system is however hampered by the temporal dimension characterizing population interactions through movements. Traditional centrality measures do not provide relevant information as results strongly fluctuate in time and outbreak properties heavily depend on geotemporal initial conditions. By focusing on the case study of cattle displacements in Italy, we aim at characterizing livestock epidemics in terms of robust features useful for planning and control, to deal with temporal fluctuations, sensitivity to initial conditions and missing information during an outbreak. Through spatial disease simulations, we detect spreading paths that are stable across different initial conditions, allowing the clustering of the seeds and reducing the epidemic variability. Paths also allow us to identify premises, called sentinels, having a large probability of being infected and providing critical information on the outbreak origin, as encoded in the clusters. This novel procedure provides a general framework that can be applied to specific diseases, for aiding risk assessment analysis and informing the design of optimal surveillance systems. PMID:22728387

Disturbed skin barrier in children with chronic kidney disease.

PubMed

Wojtowicz-Prus, Elzbieta; Kilis-Pstrusinska, Katarzyna; Reich, Adam; Zachwieja, Katarzyna; Miklaszewska, Monika; Szczepanska, Maria; Szepietowski, Jacek C

2015-02-01

There are limited data on skin lesions in children with end-stage renal failure. The aim of the study was an evaluation of the skin barrier in children with different stages of chronic kidney disease (CKD). The prevalence of xerosis, its severity, as well as its link selected demographic factors, were examined. The study included 103 children: 72 with CKD stages 3-5 (38 on conservative treatment and 34 on dialysis) and 31 patients with primary monosymptomatic nocturnal enuresis as a control group. Initially, the study subjects described the localisation and severity of dry skin by themselves. Next, clinical evaluation of xerosis, non-invasive corneometric assessment of epidermis moisturising and the measurement of transepidermal water loss were performed. Most CKD children reported dry skin. The problem of xerosis was identified more frequently in patients on dialysis (67.6 %) than on conservative treatment (42.1 %) (p = 0.01). CKD patients divided according to skin dryness did not differ with regards to age, sex, initial kidney disease and CKD duration. Disturbed skin barrier is an important concern of children with CKD, intensifying as the disease progresses. This symptom occurs on early stages of CKD and it should be taken into consideration in the CKD management.

Identification and Characterization of a Unique Fusarium sp. nov. ex Mangifera indica L. Causing Mango Malformation Disease in México

USDA-ARS?s Scientific Manuscript database

In this study we characterized fusaria that were associated with mango malformation disease (MMD) in México. From 2002 to 2009, 141 strains were isolated from symptomatic mango inflorescences and vegetative tissues from various cultivars in eight geographically diverse states. Initially, isolates ...

Pathogenesis of primary foot-and-mouth disease virus infection in the nasopharynx of vaccinated and non-vaccinated cattle

USDA-ARS?s Scientific Manuscript database

A time-course pathogenesis study was performed to compare and contrast primary foot-and-mouth disease virus (FMDV) infection in vaccinated and non-vaccinated cattle following simulated-natural virus exposure. FMDV genome and infectious virus were detected during the initial phase of infection from b...

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

Treesearch

Thomas H. Nicholls; Darroll D. Skilling

1974-01-01

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

Association between Human Body Composition and Periodontal Disease.

PubMed

Salekzamani, Yagoub; Shirmohammadi, Adileh; Rahbar, Mohammad; Shakouri, Seyed-Kazem; Nayebi, Farough

2011-01-01

Obesity in humans might increase the risk of periodontitis. The aim of the present study was to examine the relationship between body composition of males and their periodontal status. AS total of 150 males (aged 30-60) were selected: 31 were periodontally healthy, 45 had gingivitis, 39 had initial periodontitis, and 35 suffered from established periodontitis. BMI (body mass index), WC (waist circumference), and body composition parameters (consisting of body water, body fat, and skeletal muscle and bone mass) were measured. After adjusting for age, history of diabetes, smoking, physical activity status, and socioeconomic status, statistically significant correlations were found between periodontitis and BMI, WC, and body composition. There was only a statistically significant difference between the periodontal health and established periodontitis; that is, periodontal disease in mild forms (gingivitis) and initial periodontitis do not influence these variables (BMI, WC, and body composition parameters) and only the severe form of the disease influences the variables. These data suggest that there is a considerable association between severe forms of periodontal disease in males and their body composition, but this preliminary finding needs to be confirmed in more extensive studies.

Heart Failure and Frailty in the Community-Living Elderly Population: What the UFO Study Will Tell Us

PubMed Central

Fung, Erik; Hui, Elsie; Yang, Xiaobo; Lui, Leong T.; Cheng, King F.; Li, Qi; Fan, Yiting; Sahota, Daljit S.; Ma, Bosco H. M.; Lee, Jenny S. W.; Lee, Alex P. W.; Woo, Jean

2018-01-01

Heart failure and frailty are clinical syndromes that present with overlapping phenotypic characteristics. Importantly, their co-presence is associated with increased mortality and morbidity. While mechanical and electrical device therapies for heart failure are vital for select patients with advanced stage disease, the majority of patients and especially those with undiagnosed heart failure would benefit from early disease detection and prompt initiation of guideline-directed medical therapies. In this article, we review the problematic interactions between heart failure and frailty, introduce a focused cardiac screening program for community-living elderly initiated by a mobile communication device app leading to the Undiagnosed heart Failure in frail Older individuals (UFO) study, and discuss how the knowledge of pre-frailty and frailty status could be exploited for the detection of previously undiagnosed heart failure or advanced cardiac disease. The widespread use of mobile devices coupled with increasing availability of novel, effective medical and minimally invasive therapies have incentivized new approaches to heart failure case finding and disease management. PMID:29740330

The mini mental state examination at the time of Alzheimer's disease and related disorders diagnosis, according to age, education, gender and place of residence: a cross-sectional study among the French National Alzheimer database.

PubMed

Pradier, Christian; Sakarovitch, Charlotte; Le Duff, Franck; Layese, Richard; Metelkina, Asya; Anthony, Sabine; Tifratene, Karim; Robert, Philippe

2014-01-01

was firstly to describe the MMSE (Mini-Mental State Examination) score upon initial diagnosis of Alzheimer's disease and related disorders among the French population, according to age. Secondly, education, gender and place of residence were studied as factors potentially associated with delayed Alzheimer's disease diagnosis. we conducted a cross sectional analysis of the French National Alzheimer database (BNA). Data from 2008 to 2012 were extracted. Patients were selected at the moment of their first diagnosis of AD (n = 39,451). The MMSE score at initial diagnosis dropped significantly with increasing age. The test score increased with the degree of educational background regardless of age. Gender and place of residence were significantly related to the MMSE score, women and persons living in medical institutions having lower MMSE scores under the age of 90 years and at all educational levels. Health care professionals should be aware of these risk factors in order to maximize chances of earliest possible diagnosis of Alzheimer's disease and related disorders.

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

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...

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

PubMed

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

2018-01-01

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

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

GENETIC MODIFIERS OF LIVER DISEASE IN CYSTIC FIBROSIS

PubMed Central

Bartlett, Jaclyn R.; Friedman, Kenneth J.; Ling, Simon C.; Pace, Rhonda G.; Bell, Scott C.; Bourke, Billy; Castaldo, Giuseppe; Castellani, Carlo; Cipolli, Marco; Colombo, Carla; Colombo, John L.; Debray, Dominique; Fernandez, Adriana; Lacaille, Florence; Macek, Milan; Rowland, Marion; Salvatore, Francesco; Taylor, Christopher J.; Wainwright, Claire; Wilschanski, Michael; Zemková, Dana; Hannah, William B.; Phillips, M. James; Corey, Mary; Zielenski, Julian; Dorfman, Ruslan; Wang, Yunfei; Zou, Fei; Silverman, Lawrence M.; Drumm, Mitchell L.; Wright, Fred A.; Lange, Ethan M.; Durie, Peter R.; Knowles, Michael R.

2013-01-01

Context A subset (~3–5%) of patients with cystic fibrosis (CF) develops severe liver disease (CFLD) with portal hypertension. Objective To assess whether any of 9 polymorphisms in 5 candidate genes (SERPINA1, ACE, GSTP1, MBL2, and TGFB1) are associated with severe liver disease in CF patients. Design, Setting, and Participants A 2-stage design was used in this case–control study. CFLD subjects were enrolled from 63 U.S., 32 Canadian, and 18 CF centers outside of North America, with the University of North Carolina at Chapel Hill (UNC) as the coordinating site. In the initial study, we studied 124 CFLD patients (enrolled 1/1999–12/2004) and 843 CF controls (patients without CFLD) by genotyping 9 polymorphisms in 5 genes previously implicated as modifiers of liver disease in CF. In the second stage, the SERPINA1 Z allele and TGFB1 codon 10 genotype were tested in an additional 136 CFLD patients (enrolled 1/2005–2/2007) and 1088 CF controls. Main Outcome Measures We compared differences in distribution of genotypes in CF patients with severe liver disease versus CF patients without CFLD. Results The initial study showed CFLD to be associated with the SERPINA1 (also known as α1-antiprotease and α1-antitrypsin) Z allele (P value=3.3×10−6; odds ratio (OR) 4.72, 95% confidence interval (CI) 2.31–9.61), and with transforming growth factor β-1 (TGFB1) codon 10 CC genotype (P=2.8×10−3; OR 1.53, CI 1.16–2.03). In the replication study, CFLD was associated with the SERPINA1 Z allele (P=1.4×10−3; OR 3.42, CI 1.54–7.59), but not with TGFB1 codon 10. A combined analysis of the initial and replication studies by logistic regression showed CFLD to be associated with SERPINA1 Z allele (P=1.5×10−8; OR 5.04, CI 2.88–8.83). Conclusion The SERPINA1 Z allele is a risk factor for liver disease in CF. Patients who carry the Z allele are at greater odds (OR ~5) to develop severe liver disease with portal hypertension. PMID:19738092

In real life, one-quarter of patients with hormone receptor-positive metastatic breast cancer receive chemotherapy as initial palliative therapy: a study of the Southeast Netherlands Breast Cancer Consortium.

PubMed

Lobbezoo, D J A; van Kampen, R J W; Voogd, A C; Dercksen, M W; van den Berkmortel, F; Smilde, T J; van de Wouw, A J; Peters, F P J; van Riel, J M G H; Peters, N A J B; de Boer, M; Peer, P G M; Tjan-Heijnen, V C G

2016-02-01

The objective of this study was to present initial systemic treatment choices and the outcome of hormone receptor-positive (HR+) metastatic breast cancer. All the 815 consecutive patients diagnosed with metastatic breast cancer in 2007-2009 in eight participating hospitals were identified. From the 611 patients with HR+ disease, a total of 520 patients with HER2-negative (HER2-) breast cancer were included. Initial palliative systemic treatment was registered. Progression-free survival (PFS) and overall survival (OS) per initial palliative systemic therapy were obtained using the Kaplan-Meier method and compared using the log-rank test. From the total of 520 patients with HR+/HER2- metastatic breast cancer, 482 patients (93%) received any palliative systemic therapy. Patients that received initial chemotherapy (n = 116) were significantly younger, had less comorbidity, had received more prior adjuvant systemic therapy and were less likely to have bone metastasis only compared with patients that received initial endocrine therapy (n = 366). Median PFS of initial palliative chemotherapy was 5.3 months [95% confidence interval (CI) 4.2-6.2] and of initial endocrine therapy 13.3 months (95% CI 11.3-15.5), with a median OS of 16.1 and 36.9 months, respectively. Initial chemotherapy was also associated with worse outcome in terms of PFS and OS after adjustment for prognostic factors. A high percentage of patients with HR+ disease received initial palliative chemotherapy, which was associated with worse outcome, even after adjustment of relevant prognostic factors. © The Author 2015. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Alterations in DNA methylation corresponding with lung inflammation and as a biomarker for disease development after MWCNT exposure.

PubMed

Brown, Traci A; Lee, Joong Won; Holian, Andrij; Porter, Virginia; Fredriksen, Harley; Kim, Minju; Cho, Yoon Hee

2016-01-01

Use of multi-walled carbon nanotubes (MWCNT) is growing which increases occupational exposures to these materials. Their toxic potential makes it important to have an in-depth understanding of the inflammation and disease that develops due to exposure. Epigenetics is one area of interest that has been quickly developing to assess disease processes due to its ability to change gene expression and thus the lung environment after exposure. In this study, promoter methylation of inflammatory genes (IFN-γ and TNF-α) was measured after MWCNT exposure using the pyrosequencing assay and found to correlate with initial cytokine production. In addition, methylation of a gene involved in tissue fibrosis (Thy-1) was also altered in a way that matched collagen deposition. In addition to using epigenetics to better understand disease processes, it has also been used as a biomarker of exposure and disease. In this study, global methylation was determined in the lung to ascertain whether MWCNT alter global methylation at the site of exposure and if those alterations coincide with disease development. Then, global methylation levels were determined in the blood to ascertain whether global methylation could be used as a biomarker of exposure in a more easily accessible tissue. Using the LuUminometric Methylation Assay (LUMA) and 5-Methylcytosine (5-mC) Quantification assay, we found that MWCNT lead to DNA hypomethylation in the lung and blood, which coincided with disease development. This study provides initial data showing that alterations in gene-specific methylation correspond with an inflammatory response to MWCNT exposure. In addition, global DNA methylation in the lung and blood coincides with MWCNT-induced disease development, suggesting its potential as a biomarker of both exposure and disease development.

Tolerating increases in the serum creatinine following aggressive treatment of chronic kidney disease, hypertension and proteinuria: pre-renal success.

PubMed

Hirsch, Sheldon; Hirsch, Jackie; Bhatt, Udayan; Rovin, Brad H

2012-01-01

Blood pressure (BP) reduction in patients with chronic kidney disease (CKD), particularly with a renin-angiotensin system inhibitor (RASI), commonly leads to an initial decrease in glomerular filtration rate. The current clinical guideline, based on studies with single RASIs, is to tolerate an increase in the serum creatinine only up to 30%. This guideline has aptly guided CKD care for over a decade, but should be updated in the contemporary context of more aggressive RASI and diuretic use. This study is a retrospective review of 48 mostly African-American patients with CKD treated with multiple and/or high-dose renin-angiotensin system (RAS) inhibition and diuretics, targeting both low BP and reduction of urine protein. RASI was not reduced in response to initial increases in serum creatinine greater than 30%. A clinically well-tolerated increase in serum creatinine over 30% during the first year occurred in 41% of the patients. Treatment was unaltered, and target goals for BP and urine protein were typically achieved. After the point of maximal serum creatinine in the first year, these patients had minimal progression of disease over the next 6 years, with a long-term estimated glomerular filtration rate slope of only -0.52 ml/min/year/1.73 m(2). Only 25% progressed to end-stage renal disease or death. The 30% limitation to initial increases in the serum creatinine still pertains for single RASI at usual doses. However, favorable long-term outcomes suggest that initial increases over 30% should be tolerated in the context of dual goal-directed, more aggressive RASI and diuretic use. Copyright © 2012 S. Karger AG, Basel.

Epilepsy in children with subacute sclerosing panencephalitis.

PubMed

Jović, Nebojša J

2013-01-01

Subacute sclerosing panencephalitis (SSPE) is a rare, progressive, fatal neurodegenerative disease of childhood and early adolescence caused by defective measles virus. The initial symptoms of SSPE usually involve regression in cognitive functioning and behavior or recurrent myoclonic jerks. Seizures revealing SSPE and epilepsy during the clinical course can occur. The aim of the study was to analyze clinical and EEG characteristics of both initially occurred seizures and epilepsy which developed in the course of the disease. Retrospective study was carried out on 19 children (14 boys, 5 girls) with SSPE diagnosed and treated at our Clinic from 1995 to 2010. Seizures revealed SSPE in our patients aged from 6.5 to 11.5 years (mean 8.6 years). SSPE onset ranged from 4.5 to 16.5 years (mean 10.05). Complete vaccination was performed in nine patients. Cognitive and behavioral decline was preceeded by 6-18 months in two children with intractable focal motor seizures with secondary generalization, one child with complex partial seizures and one with atypical absences. During the clinical course of the disease epilepsy developed in 10 (52.6%) cases, including four patients with seizures as the initial SSPE sign. It occurred mainly in the first year, while in three cases seizures appeared between 1 and 5 years of the disease evolution. Myoclonus was present independently from seizures. No significant inter-group differences were found relating to the type of SSPE progression and history of epilepsy. The only child with fulminant SSPE presented with initial seizures. Favorable seizure control was achieved in 60.0% patients. Intractable epilepsy developed in four patients. Atypical SSPE presentation can include mainly focal intractable seizures. Epilepsy developed during clinical course in 52.6% cases. No significant influence was found of the history of epilepsy on the type of SSPE progression.

Metabolic network failures in Alzheimer’s disease: A biochemical road map

PubMed Central

Toledo, Jon B.; Arnold, Matthias; Kastenmüuller, Gabi; Chang, Rui; Baillie, Rebecca A.; Han, Xianlin; Thambisetty, Madhav; Tenenbaum, Jessica D.; Suhre, Karsten; Thompson, J. Will; St. John-Williams, Lisa; MahmoudianDehkordi, Siamak; Rotroff, Daniel M.; Jack, John R.; Motsinger-Reif, Alison; Risacher, Shannon L.; Blach, Colette; Lucas, Joseph E.; Massaro, Tyler; Louie, Gregory; Zhu, Hongjie; Dallmann, Guido; Klavins, Kristaps; Koal, Therese; Kim, Sungeun; Nho, Kwangsik; Shen, Li; Casanova, Ramon; Varma, Sudhir; Legido-Quigley, Cristina; Moseley, M. Arthur; Zhu, Kuixi; Henrion, Marc Y. R.; van der Lee, Sven J.; Harms, Amy C.; Demirkan, Ayse; Hankemeier, Thomas; van Duijn, Cornelia M.; Trojanowski, John Q.; Shaw, Leslie M.; Saykin, Andrew J.; Weiner, Michael W.; Doraiswamy, P. Murali; Kaddurah-Daouk, Rima

2018-01-01

Introduction The Alzheimer’s Disease Research Summits of 2012 and 2015 incorporated experts from academia, industry, and nonprofit organizations to develop new research directions to transform our understanding of Alzheimer’s disease (AD) and propel the development of critically needed therapies. In response to their recommendations, big data at multiple levels are being generated and integrated to study network failures in disease. We used metabolomics as a global biochemical approach to identify peripheral metabolic changes in AD patients and correlate them to cerebrospinal fluid pathology markers, imaging features, and cognitive performance. Methods Fasting serum samples from the Alzheimer’s Disease Neuroimaging Initiative (199 control, 356 mild cognitive impairment, and 175 AD participants) were analyzed using the AbsoluteIDQ-p180 kit. Performance was validated in blinded replicates, and values were medication adjusted. Results Multivariable-adjusted analyses showed that sphingomyelins and ether-containing phosphatidylcholines were altered in preclinical biomarker-defined AD stages, whereas acylcarnitines and several amines, including the branched-chain amino acid valine and α-aminoadipic acid, changed in symptomatic stages. Several of the analytes showed consistent associations in the Rotterdam, Erasmus Rucphen Family, and Indiana Memory and Aging Studies. Partial correlation networks constructed for Aβ1–42, tau, imaging, and cognitive changes provided initial biochemical insights for disease-related processes. Coexpression networks interconnected key metabolic effectors of disease. Discussion Metabolomics identified key disease-related metabolic changes and disease-progression-related changes. Defining metabolic changes during AD disease trajectory and its relationship to clinical phenotypes provides a powerful roadmap for drug and biomarker discovery. PMID:28341160

A highly accurate method for monitoring histological recovery in patients with celiac disease on a gluten-free diet using an endoscopic approach that avoids the need for biopsy: a double-center study.

PubMed

Cammarota, G; Cuoco, L; Cesaro, P; Santoro, L; Cazzato, A; Montalto, M; La Mura, R; Larocca, L M; Vecchio, F M; Gasbarrini, A; Salvagnini, M; Gasbarrini, G

2007-01-01

Endoscopy with duodenal biopsy is often performed in order to assess histological recovery in patients with celiac disease who are on a gluten-free diet. Use of the "immersion" technique during upper endoscopy allows visualization of duodenal villi or detection of total villous atrophy. In this two-center study, we investigated the accuracy of the immersion technique in predicting histological recovery in patients on a gluten-free diet whose initial diagnosis of celiac disease had been made on the basis of total villous atrophy. The immersion technique was performed in 62 patients with celiac disease who were being treated and who had been referred for follow-up (26 patients at the Rome center and 36 patients at the Vicenza center). All these patients had an initial diagnosis based on positive antibodies and biopsy-proved duodenal total villous atrophy. At the follow-up examination, the duodenal villi were re-evaluated as present or absent by one endoscopist at each center, and the results were compared with the histology. At the follow-up endoscopy, the duodenal villi were found to be present in 51 patients and absent in 11. The sensitivity, specificity, positive predictive value, and negative predictive value of the immersion technique for detecting the presence or absence of villi were all 100 %. This study demonstrated the feasibility and the high level of accuracy of the immersion technique in predicting the histological recovery of duodenal villi in patients with celiac disease who are following a gluten-free diet. An endoscopy-based approach that avoids the need for biopsy could be useful for monitoring the dietary adherence and/or response of patients with an initial diagnosis of celiac disease based on total villous atrophy.

Crohn's disease patients carrying Nod2/CARD15 gene variants have an increased and early need for first surgery due to stricturing disease and higher rate of surgical recurrence.

PubMed

Alvarez-Lobos, Manuel; Arostegui, Juan I; Sans, Miquel; Tassies, Dolors; Plaza, Susana; Delgado, Salvadora; Lacy, Antonio M; Pique, Josep M; Yagüe, Jordi; Panés, Julián

2005-11-01

To study the predictive value of Nod2/CARD15 gene variants along with disease phenotypic characteristics for requirement of initial surgery and for surgical recurrence in Crohn's disease (CD). Nod2/CARD15 gene variants play an important role in the susceptibility to CD. Studies of genotype-phenotype relationship suggest that these variants are associated with development of intestinal strictures. Preliminary reports analyzing the association between these variants and need for surgery have produced inconsistent results. A total of 170 CD patients were included prospectively in the study and followed up regularly for a mean of 7.4 +/- 6.1 years. Clinical characteristics of CD, time and indication for surgery, and recurrence were registered. Nod2/CARD15 gene variants were determined by DNA sequencing analysis. Surgery for stricturing disease was significantly more frequent in patients with Nod2/CARD15 variants in the univariate analysis (odds ratio [OR], 3.63; 95% confidence interval [CI], 1.42-9.27), and it was required at an earlier time (P = 0.004). Only Nod2/CARD15 variants (OR, 3.58; 95% CI, 1.21-10.5) and stricturing phenotype at diagnosis of CD (OR, 9.34; 95% CI, 2.56-33.3) were independent predictive factors of initial surgery for stricturing lesions in the multivariate analysis. Among 70 patients that required surgery, postoperative recurrence was also more frequent in patients with Nod2/CARD15 variants in the univariate and multivariate analysis (OR, 3.29; 95% CI, 1.13-9.56), and reoperation was needed at an earlier time (P = 0.03). Nod2/CARD15 variants are associated with early initial surgery due to stenosis and with surgical recurrence in Crohn's disease. Patients with these variants could benefit from preventive and/or early therapeutic strategies.

Treating iron deficiency in patients with gastrointestinal disease: Risk of re-attendance in secondary care.

PubMed

Tomkins, Susannah; Chapman, Callum; Myland, Melissa; Tham, Rachel; de Nobrega, Rachael; Jackson, Brinley; Keshav, Satish

2017-01-01

Patients with gastrointestinal disease may have comorbid iron deficiency anaemia (IDA) and an increased risk of hospitalisation and re-attendance in hospital. The purpose of this study was to determine if oral and intravenous (IV) treatment of IDA in patients with gastrointestinal disease attending hospital were associated with differential rates of subsequent re-attendance. Data from the Clinical Practice Research Datalink (primary care) and Hospital Treatment Insights (secondary care) databases in England were used to conduct this retrospective cohort study. Patients with a coded gastrointestinal disease and IDA who attended hospital (inpatient or outpatient) and were dispensed oral or IV iron between 01/01/2010-31/10/2013 were included. Elective and emergency re-attendances in secondary care within 30 days of the initial attendance were determined. Demographics, medical diagnoses and treatments were extracted. Re-attendance rates following oral or IV iron were compared using chi-square tests and a step-wise logistic regression model to adjust for confounders. 2,844 patients contributed 6,294 initial attendances; 80% of patients received oral iron, 14% received intravenous iron, and 6% received both. Of initial attendances recording oral iron, 77% resulted in re-attendance in hospital, compared to 34% of those recording IV iron (unadjusted odds ratio [OR]: 0.16; adjusted OR: 0.52 [95% CI: 0.44-0.61]). Initial attendances using IV treatment were more likely to result in elective re-attendance (84%) than those recording oral treatment (43%) (p<0.001). Median length of stay in hospital tended to be shorter for patients using IV iron (1.4 days; interquartile range 0.5-3.6 days; oral iron: 5.1 days; interquartile range: 2.2-9.6 days). Patients with gastrointestinal disease and IDA who received IV iron were less likely to re-attend hospital, more likely to re-attend electively, and tended to have a shorter length of stay in hospital. The mode of IDA treatment could have a real-world impact on healthcare utilisation.

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...

The European Respiratory Society study on chronic obstructive pulmonary disease (EUROSCOP): recruitment methods and strategies.

PubMed

Löfdahl, C G; Postma, D S; Laitinen, L A; Ohlsson, S V; Pauwels, R A; Pride, N B

1998-03-01

The European Respiratory Society's study on chronic obstructive pulmonary disease (EUROSCOP) is a multicentre study performed initially in 12 countries to assess the effect of 3 years' treatment with inhaled corticosteroids on lung function decline in smokers with chronic obstructive pulmonary disease (COPD). It aimed at recruiting 50 subjects in 50 European centres. This study discusses the most successful, countrywise, recruitment strategies, an important issue since many multicentre European studies may follow in the future. The total number of recruited subjects was 2147 in 39 participating centres. In total, at least 25,000 screening spirometries were performed, and about 80,000 hospital records were checked. The most effective way of recruiting subjects was to screen subjects by spirometry after mass media campaigns (eight out of nine countries). Others used workplace screenings and different types of population survey, and only a few centres successfully recruited participants by hospital records. Inclusion criteria were slightly changed upon low initial accrual rate. Initial surveys in one country, where 2405 subjects were screened by spirometry, gave an important indication for the change of the inclusion criteria. Extension of the upper age limit from 60 to 65 yr considerably improved recruitment, as did a change of the upper limit of FEV1 from below 80% predicted normal to below 100% predicted normal, while maintaining the FEV1/VC ratio below 70%. A tremendous effort is needed to recruit individuals with preclinical COPD, but this is certainly feasible with adequate strategies adjusted to each country.

Treatment Patterns and Burden of Illness in Patients Initiating Targeted Therapy or Chemotherapy for Pancreatic Neuroendocrine Tumors.

PubMed

Broder, Michael S; Chang, Eunice; Reddy, Sheila R; Neary, Maureen P

2017-08-01

The aim of this study was to characterize treatment patterns and burden of pancreatic neuroendocrine tumors (PNET). Using 2 claims databases, we identified patients with PNET initiating targeted therapy (everolimus, sunitinib) or chemotherapy from 2009 to 2012. The first targeted/cytotoxic therapy was considered index treatment. Treatment patterns were graphically evaluated from index treatment initiation until enrollment or study end, whichever occurred first. Disease burden was examined by index group for first follow-up year. In treatment pattern analyses (582 newly treated patients with PNET), 72.2% received chemotherapy index treatment, 16.2% everolimus, and 11.7% received sunitinib. Median index treatment duration was 242, 146, and 126 days for everolimus, sunitinib, and cytotoxics (P < 0.01). Sunitinib initiators switched most often followed by everolimus and cytotoxic initiators. In disease burden analyses, 338 patients met inclusion criteria, with mean age of 54.5 (standard deviation, 9.9) years, 45.6% were female, and there were no significant between-group differences. Targeted therapy initiators had more prior somatostatin analog use versus cytotoxics (53.4% vs 25.1%, P < 0.001); 72.5% had comorbidities after treatment initiation; 42.9% had 1 or more inpatient hospitalization; and 47.9% had 1 or more emergency department visit. Pancreatic neuroendocrine tumor treatment patterns varied; cytotoxics were more often used as early therapy than targeted agents, but for less time. Patients had high health care utilization, irrespective of treatment, potentially from burdensome symptoms and comorbidities.

[Central nervous tuberculosis in patients non-VIH: seven case reports].

PubMed

Mazodier, K; Bernit, E; Faure, V; Rovery, C; Gayet, S; Seux, V; Donnet, A; Brouqui, P; Disdier, P; Schleinitz, N; Kaplanski, G; Veit, V; Harlé, J-R

2003-02-01

Tuberculosis involving the central nervous system (CNS) is rarely observed in non immuno-compromised hosts. We report herin the various clinical, biological and radiological manifestations observed in 7 patients with CNS tuberculosis. Clinical and biological records of 7 patients with CNS tuberculosis were retrospectively studied. All patients had encephalic CT-scan and MRI in the course of the disease. 5 women and 2 men with a mean age of 38.4 years initially initially presented with headache (n = 6), fever (n = 5), meningeal irritation (n = 3), localizing neurological signs (n = 1). Lumbar punction revealed lymphocytic meningitis (n = 6/7). Mycobacterium tuberculosis or bovis was isolated in 3 patients only. Cerebral tomodensitography or magnetic resonance imaging were initially normal in most of cases (n = 4/7), but discovered in the course of disease basilar meningitis (n = 6), hydrocephalus (n = 6), abcess or tuberculoma (n = 4). In all the patients, initiation of the treatment was complicated by clinical and/or biological deterioration, called paradoxal reaction, leading in all cases to glucocorticoid adjunction, with various final results. Indeed, 4 patients developed neurological sequelae. No patient died. CNS tuberculosis is a rare disease in non immunocompromised patients whose diagnostic may be difficult due to the absence of specific clinical symptoms, negative initial radiological examination, as well as delayed and often negative bacterial isolation. Paradoxal reaction appeared to be frequent despite specific antibiotherapy and underlines the beneficial effects of addictive corticosteroids.

"I Love Fruit But I Can't Afford It": Using Participatory Action Research to Develop Community-Based Initiatives to Mitigate Challenges to Chronic Disease Management in an African American Community Living in Public Housing.

PubMed

Rogers, Courtney; Johnson, Joy; Nueslein, Brianne; Edmunds, David; Valdez, Rupa S

2018-03-12

As chronic conditions are on the rise in the USA, management initiatives outside of the inpatient setting should be explored to reduce associated cost and access disparities. Chronic conditions disproportionately affect African American public housing residents due to the effects of historical marginalization on the manifestation of economic and social problems exacerbating health disparities and outcomes. Informed by participatory research action tenets, this study focused on identifying the challenges to management of chronic conditions and developing community-envisioned initiatives to address these challenges in a predominantly African American public housing community. Two focus groups were conducted with former and current public housing residents and were analyzed using inductive content analysis. Physical activity, the cost associated with healthy eating, and lack of information were noted as challenges to chronic disease management. Initiatives discussed were the formation of a walking partner's program to promote physical activity, a shopper's club to exchange coupons and learn how to prepare healthy meals, and a natural remedy's book to share information intergenerationally about management tactics. Challenges identified existed predominantly on the individual and the system level, while the initiatives generated target engaging interpersonal and community relationships. These community-envisioned approaches should be explored to facilitate chronic disease management in public housing neighborhoods.

Adult Congenital Heart Disease Patients Experience Similar Symptoms of Disease Activity.

PubMed

Cedars, Ari M; Stefanescu Schmidt, Ada; Broberg, Craig; Zaidi, Ali; Opotowsky, Alexander; Grewal, Jasmine; Kay, Joseph; Bhatt, Ami B; Novak, Eric; Spertus, John

2016-03-01

There is a lack of objective data on the symptoms characterizing disease activity among adults with congenital heart disease (ACHD). The purpose of this study was to elicit the most important symptoms from patients across the spectrum of ACHD and to examine whether reported symptoms were similar across the spectrum of ACHD as a foundation for creating a patient-reported outcome measure(s). We constructed a 39-item survey using input from physicians specializing in ACHD to assess the symptoms patients associate with disease activity. Patients (n=124) prospectively completed this survey, and the results were analyzed based on underlying anatomy and disease complexity. A confirmatory cohort of patients (n=40) was then recruited prospectively to confirm the validity of the initial data. When grouped based on underlying anatomy, significant differences in disease-related symptom rankings were found for only 6 of 39 symptoms. Six symptoms were identified which were of particular significance to patients, regardless of underlying anatomy. Patients with anatomy of great complexity experienced greater overall symptom severity than those with anatomy of low or moderate complexity, attributable exclusively to higher ranking of 5 symptoms. The second patient cohort had symptom experiences similar to those of the initial cohort, differing in only 5 of 39 symptoms. This study identified 6 symptoms relevant to patients across the spectrum of ACHD and remarkable homogeneity of patient experience, suggesting that a single disease-specific patient-reported outcome can be created for quality and outcome assessments. © 2016 American Heart Association, Inc.

Treatment patterns in disease-modifying therapy for patients with multiple sclerosis in the United States.

PubMed

Bonafede, Machaon M; Johnson, Barbara H; Wenten, Madé; Watson, Crystal

2013-10-01

Patients with multiple sclerosis (MS) whose disease activity is inadequately controlled with a platform therapy (interferon beta or glatiramer acetate [GA]) may switch to another platform therapy or escalate therapy to natalizumab or fingolimod, which were approved in the US in 2006 and 2010, respectively. The objective of this study was to describe treatment patterns in patients with multiple sclerosis (MS) in the United States who were followed for 2 years after initiating a disease-modifying therapy (DMT). A retrospective observational cohort study was conducted to examine treatment patterns of initial DMT use (on initial therapy for 2 years with and without gaps of ≥ 60 days, medication switching, and discontinuation) among patients with MS who initiated a platform therapy (interferon-β or glatiramer acetate) or natalizumab between January 1, 2007, and September 30, 2009; the first DMT claim was the index. Eligible patients were identified in the MarketScan Commercial and Medicare Supplemental databases based on continuous enrollment for 6 months before (preindex period) and 24 months after their index date, with a diagnosis of MS and no claim for a previous DMT in the 6-month preindex period. Demographics at index and clinical characteristics during the preindex period were also analyzed. A total of 6181 MS patients were included, with 5735 (92.8%) starting on platform therapy. Natalizumab initiators were more likely to stay on index therapy (32.3% vs 16.9%, P < 0.001) and have fewer treatment gaps of ≥ 60 days (44.8% vs 55.3%, P < 0.001) compared with platform initiators. In addition, natalizumab initiators were less likely to switch treatment (13.9% vs 19.1%, P = 0.007) and took longer to switch (400.9 days vs 330.7 days, P < 0.001) compared with platform initiators. Nearly 79% of platform initiators who switched went to another platform therapy. Approximately two thirds of patients who switched to a third DMT (n = 130) switched to another platform therapy. A total of 9% of natalizumab and platform initiators discontinued DMT within the 2 years. Most MS patients initiating DMT started on platform therapy. Natalizumab initiators tended to stay on index therapy, have fewer treatment gaps, and switch less than platform initiators in the 2 years after treatment initiation. Switching between platform therapies is common despite evidence that MS patients on platform therapy may benefit from switching to natalizumab. © 2013 Elsevier HS Journals, Inc. All rights reserved.

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.

Trends in Prevalence of Advanced HIV Disease at Antiretroviral Therapy Enrollment - 10 Countries, 2004-2015.

PubMed

Auld, Andrew F; Shiraishi, Ray W; Oboho, Ikwo; Ross, Christine; Bateganya, Moses; Pelletier, Valerie; Dee, Jacob; Francois, Kesner; Duval, Nirva; Antoine, Mayer; Delcher, Chris; Desforges, Gracia; Griswold, Mark; Domercant, Jean Wysler; Joseph, Nadjy; Deyde, Varough; Desir, Yrvel; Van Onacker, Joelle Deas; Robin, Ermane; Chun, Helen; Zulu, Isaac; Pathmanathan, Ishani; Dokubo, E Kainne; Lloyd, Spencer; Pati, Rituparna; Kaplan, Jonathan; Raizes, Elliot; Spira, Thomas; Mitruka, Kiren; Couto, Aleny; Gudo, Eduardo Samo; Mbofana, Francisco; Briggs, Melissa; Alfredo, Charity; Xavier, Carla; Vergara, Alfredo; Hamunime, Ndapewa; Agolory, Simon; Mutandi, Gram; Shoopala, Naemi N; Sawadogo, Souleymane; Baughman, Andrew L; Bashorun, Adebobola; Dalhatu, Ibrahim; Swaminathan, Mahesh; Onotu, Dennis; Odafe, Solomon; Abiri, Oseni Omomo; Debem, Henry H; Tomlinson, Hank; Okello, Velephi; Preko, Peter; Ao, Trong; Ryan, Caroline; Bicego, George; Ehrenkranz, Peter; Kamiru, Harrison; Nuwagaba-Biribonwoha, Harriet; Kwesigabo, Gideon; Ramadhani, Angela A; Ng'wangu, Kahemele; Swai, Patrick; Mfaume, Mohamed; Gongo, Ramadhani; Carpenter, Deborah; Mastro, Timothy D; Hamilton, Carol; Denison, Julie; Wabwire-Mangen, Fred; Koole, Olivier; Torpey, Kwasi; Williams, Seymour G; Colebunders, Robert; Kalamya, Julius N; Namale, Alice; Adler, Michelle R; Mugisa, Bridget; Gupta, Sundeep; Tsui, Sharon; van Praag, Eric; Nguyen, Duc B; Lyss, Sheryl; Le, Yen; Abdul-Quader, Abu S; Do, Nhan T; Mulenga, Modest; Hachizovu, Sebastian; Mugurungi, Owen; Barr, Beth A Tippett; Gonese, Elizabeth; Mutasa-Apollo, Tsitsi; Balachandra, Shirish; Behel, Stephanie; Bingham, Trista; Mackellar, Duncan; Lowrance, David; Ellerbrock, Tedd V

2017-06-02

Monitoring prevalence of advanced human immunodeficiency virus (HIV) disease (i.e., CD4+ T-cell count <200 cells/μL) among persons starting antiretroviral therapy (ART) is important to understand ART program outcomes, inform HIV prevention strategy, and forecast need for adjunctive therapies.* , † , § To assess trends in prevalence of advanced disease at ART initiation in 10 high-burden countries during 2004-2015, records of 694,138 ART enrollees aged ≥15 years from 797 ART facilities were analyzed. Availability of national electronic medical record systems allowed up-to-date evaluation of trends in Haiti (2004-2015), Mozambique (2004-2014), and Namibia (2004-2012), where prevalence of advanced disease at ART initiation declined from 75% to 34% (p<0.001), 73% to 37% (p<0.001), and 80% to 41% (p<0.001), respectively. Significant declines in prevalence of advanced disease during 2004-2011 were observed in Nigeria, Swaziland, Uganda, Vietnam, and Zimbabwe. The encouraging declines in prevalence of advanced disease at ART enrollment are likely due to scale-up of testing and treatment services and ART-eligibility guidelines encouraging earlier ART initiation. However, in 2015, approximately a third of new ART patients still initiated ART with advanced HIV disease. To reduce prevalence of advanced disease at ART initiation, adoption of World Health Organization (WHO)-recommended "treat-all" guidelines and strategies to facilitate earlier HIV testing and treatment are needed to reduce HIV-related mortality and HIV incidence.

Renal Lymphoma: Primary or First Manifestation of Aggressive Pediatric B-cell Lymphoma.

PubMed

Coca, Pragnya; Linga, Vijay Gandhi; Gundeti, Sadashivudu; Tandon, Ashwani

2017-01-01

Renal lymphoma is an uncommon renal tumor in children. Unlike renal lymphomas presenting as bilateral disease and renal failure, we report a boy who presented with unilateral renal involvement. After initial nephrectomy, he achieved remission with multiagent chemotherapy but relapsed systemically within 3 months. He was initiated on salvage chemotherapy with autologous bone marrow transplant. Even though the initial manifestation was localized lymphoma eventually, it turned out to be a systemic disease. He succumbed to disease at 14 months from diagnosis.

Yellow Fever outbreak in Darfur, Sudan in October 2012; the initial outbreak investigation report.

PubMed

Soghaier, Mohammed A; Hagar, Ahmed; Abbas, Mohammed A; Elmangory, Mutasim M; Eltahir, Khalid M; Sall, Amadou A

2013-10-01

Sudan is subject to repeated outbreaks, including Viral Hemorrhagic Fever (VHF), which is considered to be a very serious illness. Yellow Fever (YF) outbreaks in Sudan have been reported from the 1940s through 2005. In 2012, a new outbreak of YF occurred in the Darfur region. To identify the potential for an outbreak, to diagnose the disease and to be able to recognize its cause among the initial reported cases. >This is a descriptive and investigative field study that applies standard communicable disease outbreak investigation steps. The study involved clinical, serological, entomological and environmental surveys. The field investigation confirmed the outbreak and identified its cause to be YF. National surveillance systems should be strong enough to detect VHFs in a timely manner. Local health facilities should be prepared to promptly treat the initial cases because the case fatality ratios (CFRs) are usually very high among the index cases. Copyright © 2013 King Saud Bin Abdulaziz University for Health Sciences. Published by Elsevier Ltd. All rights reserved.

Social media methods for studying rare diseases.

PubMed

Schumacher, Kurt R; Stringer, Kathleen A; Donohue, Janet E; Yu, Sunkyung; Shaver, Ashley; Caruthers, Regine L; Zikmund-Fisher, Brian J; Fifer, Carlen; Goldberg, Caren; Russell, Mark W

2014-05-01

For pediatric rare diseases, the number of patients available to support traditional research methods is often inadequate. However, patients who have similar diseases cluster "virtually" online via social media. This study aimed to (1) determine whether patients who have the rare diseases Fontan-associated protein losing enteropathy (PLE) and plastic bronchitis (PB) would participate in online research, and (2) explore response patterns to examine social media's role in participation compared with other referral modalities. A novel, internet-based survey querying details of potential pathogenesis, course, and treatment of PLE and PB was created. The study was available online via web and Facebook portals for 1 year. Apart from 2 study-initiated posts on patient-run Facebook pages at the study initiation, all recruitment was driven by study respondents only. Response patterns and referral sources were tracked. A total of 671 respondents with a Fontan palliation completed a valid survey, including 76 who had PLE and 46 who had PB. Responses over time demonstrated periodic, marked increases as new online populations of Fontan patients were reached. Of the responses, 574 (86%) were from the United States and 97 (14%) were international. The leading referral sources were Facebook, internet forums, and traditional websites. Overall, social media outlets referred 84% of all responses, making it the dominant modality for recruiting the largest reported contemporary cohort of Fontan patients and patients who have PLE and PB. The methodology and response patterns from this study can be used to design research applications for other rare diseases. Copyright © 2014 by the American Academy of Pediatrics.

[Surviving the initial phase: subjective theories of illness in patients suffering from acute leukaemia at the end of initial inpatient treatment].

PubMed

Koehler, Katharina; Dogan, Elif; Koehler, Michael; Heine, Viktoria; Frommer, Jörg

2011-01-01

Studies concentrating on the temporal dependence of subjective concepts during oncological treatment are underrepresented. Subjective interpretation contexts develop in the course of illness. The study focuses on the ideal-typical gestalt of these contents. In a follow-up study on coping, 12 patients with acute leukaemia (AL) were interviewed using a semistructured interview at the end of initial inpatient treatment. Using qualitative methodology, we inductively developed categories and assigned them to formal main categories. The following categories were developed: causal uncertainty as burden; discrepancy between subjective and objective assessment of degree of threat; knowledge of disease: conflict between information-seeking and information-avoiding behavior; dominance of medical approach to treatment; pursuit of normality; defense of emotions; orientation to workflows on the ward; adjustment as a coping strategy; positive attitude as a resource; life between hope and fear; limited future; latent fear of death. Themes of coping with the disease become visible. Some of these contents are tacit and latent, although of high subjective relevance to the patient. Their consideration could improve the patient-physician relationship.

Moderating factors influencing adoption of a mobile chronic disease management system in China.

PubMed

Zhu, Zhangxiang; Liu, Yongmei; Che, Xiaoling; Chen, Xiaohong

2018-01-01

Mobile chronic disease management systems (MCDMS) have become increasingly important in recent years, but in China, challenges remain for their adoption. Existing empirical studies have not completely explored the adoption behavior of potential MCDMS users. This article presents a study in which we investigated factors that influence chronically ill patients in China and their families to adopt or decline to use MCDMS. We applied a research model based on the technology acceptance model (TAM) as well as four contextual constructs (perceived disease threat, perceived risk, initial trust, and technology anxiety) to a survey of 279 potential MCDMS service participants in China. Our key findings include: (1) as consistent with current research, both perceived usefulness and perceived ease of use have positive impact on potential users' MCDMS adoption intention; (2) both perceived disease threat and initial trust have positive impact on MCDMS adoption intention; (3) the impact of perceived risk is negative, and technology anxiety has negative impact on perceived ease of use of MCDMS; (4) young people place more importance on their perceptions of usefulness, ease of operation, and disease threat than middle-aged and older users; (5) family members are more influenced by their perception of ease of use and disease threat than chronically ill patients, while chronically ill patients place more importance on perceived usefulness than family members. This article concludes by discussing the implications of our study for research and practice, as well as limitations and future research directions.

Alzheimer’s Disease and Its Treatment With a Novel Transdermal Patch Therapy: Survey of Caregiver Experiences

PubMed Central

Pepp, Mike

2012-01-01

Objective: To investigate experiences and perceptions of caregivers of patients with Alzheimer’s disease using transdermal patch therapy. Method: Assessment methods for the pilot study comprised an interview between the caregiver and a moderator, an interview between 1 moderator and 2 caregivers, or a video diary. The subsequent quantitative study involved a 45-minute telephone questionnaire. For both studies, participants were required to be the principal caregiver of a patient with Alzheimer’s disease who had been receiving transdermal patch therapy for at least 3 months. Their responses were grouped into the following 6 themes: interpersonal relationships, impact on caregivers, from symptoms to treatment, help and support for caregivers, daily routine, and caregiver experience with the patch. Results: Overall, 206 caregivers were enrolled from France, Germany, Greece, Spain, and the United States between July 2009 and January 2011 (pilot study: N = 56; quantitative study: N = 150). The studies revealed that caregivers of patients with Alzheimer’s disease experienced emotional and practical impacts, and many felt that they had not received sufficient information from health care providers about Alzheimer’s disease, treatment options, or available support. In the quantitative study, 47% of caregivers who had been caring for the patient prior to diagnosis (61% of total respondents) felt that there had been a delay in seeking medical advice, frequently due to slow onset of symptoms of Alzheimer’s disease. In both studies, patch therapy was considered more convenient and easier to administer than oral treatments. The practical and efficacy advantages of the patch often translated into emotional benefits. Conclusions: With recent data highlighting the importance of early initiation of symptomatic Alzheimer’s disease therapy and the importance of reaching an optimal therapeutic dose, reasons for delay in treatment initiation need to be explored. Information that patients and caregivers receive at the time of diagnosis may aid therapeutic decisions. PMID:23251856

76 FR 18555 - Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Initial Review

Federal Register 2010, 2011, 2012, 2013, 2014

2011-04-04

... announced below concerns Economic Studies of Vaccines and Immunization Policies, Programs, and Practices... to ``Economic Studies of Vaccines and Immunization Policies, Programs, and Practices, FOA IP11-007...

Patterns of Lung Volume Use during an Extemporaneous Speech Task in Persons with Parkinson Disease

ERIC Educational Resources Information Center

Bunton, K.

2005-01-01

This study examined patterns of lung volume use in speakers with Parkinson disease (PD) during an extemporaneous speaking task. The performance of a control group was also examined. Behaviors described are based on acoustic, kinematic and linguistic measures. Group differences were found in breath group duration, lung volume initiation, and lung…

[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 Global Spine Care Initiative: a summary of the global burden of low back and neck pain studies.

PubMed

Hurwitz, Eric L; Randhawa, Kristi; Yu, Hainan; Côté, Pierre; Haldeman, Scott

2018-02-26

This article summarizes relevant findings related to low back and neck pain from the Global Burden of Disease (GBD) reports for the purpose of informing the Global Spine Care Initiative. We reviewed and summarized back and neck pain burden data from two studies that were published in Lancet in 2016, namely: "Global, regional, and national incidence, prevalence, and years lived with disability for 310 diseases and injuries, 1990-2015: a systematic analysis for the Global Burden of Disease Study 2015" and "Global, regional, and national disability-adjusted life years (DALYs) for 315 diseases and injuries and healthy life expectancy (HALE), 1990-2015: a systematic analysis for the Global Burden of Disease Study 2015." In 2015, low back and neck pain were ranked the fourth leading cause of disability-adjusted life years (DALYs) globally just after ischemic heart disease, cerebrovascular disease, and lower respiratory infection {low back and neck pain DALYs [thousands]: 94 941.5 [95% uncertainty interval (UI) 67 745.5-128 118.6]}. In 2015, over half a billion people worldwide had low back pain and more than a third of a billion had neck pain of more than 3 months duration. Low back and neck pain are the leading causes of years lived with disability in most countries and age groups. Low back and neck pain prevalence and disability have increased markedly over the past 25 years and will likely increase further with population aging. Spinal disorders should be prioritized for research funding given the huge and growing global burden. These slides can be retrieved under Electronic Supplementary Material.

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.

Management Options for Biochemically Recurrent Prostate Cancer.

PubMed

Fakhrejahani, Farhad; Madan, Ravi A; Dahut, William L

2017-05-01

Prostate cancer is the most common solid tumor malignancy in men worldwide. Treatment with surgery and radiation can be curative in organ-confined disease. Unfortunately, about one third of men develop biochemically recurrent disease based only on rising prostate-specific antigen (PSA) in the absence of visible disease on conventional imaging. For these patients with biochemical recurrent prostate cancer, there is no uniform guideline for subsequent management. Based on available data, it seems prudent that biochemical recurrent prostate cancer should initially be evaluated for salvage radiation or prostatectomy, with curative intent. In selected cases, high-intensity focused ultrasound and cryotherapy may be considered in patients that meet very narrow criteria as defined by non-randomized trials. If salvage options are not practical or unsuccessful, androgen deprivation therapy (ADT) is a standard option for disease control. While some patients prefer ADT to manage the disease immediately, others defer treatment because of the associated toxicity. In the absence of definitive randomized data, patients may be followed using PSA doubling time as a trigger to initiate ADT. Based on retrospective data, a PSA doubling time of less than 3-6 months has been associated with near-term development of metastasis and thus could be used signal to initiate ADT. Once treatment is begun, patients and their providers can choose between an intermittent and continuous ADT strategy. The intermittent approach may limit side effects but in patients with metastatic disease studies could not exclude a 20% greater risk of death. In men with biochemical recurrence, large studies have shown that intermittent therapy is non-inferior to continuous therapy, thus making this a reasonable option. Since biochemically recurrent prostate cancer is defined by technological limitations of radiographic detection, as new imaging (i.e., PSMA) strategies are developed, it may alter how the disease is monitored and perhaps managed. Furthermore, patients have no symptoms related to their disease and thus many prefer options that minimize toxicity. For this reason, herbal agents and immunotherapy are under investigation as potential alternatives to ADT and its accompanying side effects. New therapeutic options combined with improved imaging to evaluate the disease may markedly change how biochemically recurrent prostate cancer is managed in the future.

Incompletely treated malignancies of the major salivary gland: Toward evidence-based care.

PubMed

Tam, Samantha; Sandulache, Vlad C; Metwalli, Kareem A; Rock, Crosby D; Eraj, Salman A; Sheu, Tommy; El-Naggar, Adel K; Fuller, Clifton D; Weber, Randal S; Lai, Stephen Y

2018-05-07

Unexpected malignancy is common in major salivary gland tumors due to variability of workup, creating challenging treatment decisions. The purpose of this study was to define treatment-related outcomes for patients with incompletely treated major salivary gland tumors. A retrospective cohort study was completed of patients with incompletely treated major salivary gland tumors. Tumor burden at presentation was established and treatment categorized. The Cox Proportional Hazards model was used to determine predictors of survival and failure. Of the 440 included patients, patients with gross residual or metastatic disease had a worse overall survival (OS; P < .001). Presentation status was an independent predictor of OS on multivariate analysis (gross residual disease adjusted hazard ratio [HR adjusted ] 2.55; 95% confidence interval [CI] 1.20-5.30; metastatic disease HR adjusted 9.53; 95% CI 3.04-27.06). Failure to achieve gross total resection during initial surgery resulted in worse OS. Adequate preoperative planning is required for initial surgical management to optimize tumor control and survival. © 2018 Wiley Periodicals, Inc.

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...

Benefits and Risks of Postmenopausal Hormone Therapy When It Is Initiated Soon After Menopause

PubMed Central

Manson, JoAnn E.; Langer, Robert D.; Anderson, Garnet L.; Pettinger, Mary; Jackson, Rebecca D.; Johnson, Karen C.; Kuller, Lewis H.; Lane, Dorothy S.; Wactawski-Wende, Jean; Brzyski, Robert; Allison, Matthew; Ockene, Judith; Sarto, Gloria; Rossouw, Jacques E.

2009-01-01

The authors further analyzed results from the Women's Health Initiative randomized trials (1993–2004) of conjugated equine estrogens, with or without medroxyprogesterone acetate, focusing on health benefits versus risks among women who initiated hormone therapy soon after menopause. Data from the Women's Health Initiative observational study (1993–2004) were included in some analyses for additional precision. Results are presented here for incident coronary heart disease, stroke, venous thromboembolism, breast cancer, colorectal cancer, endometrial cancer, or hip fracture; death from other causes; a summary global index; total cancer; and total mortality. Hazard ratios for breast cancer and total cancer were comparatively higher (P < 0.05) among women who initiated hormone therapy soon after menopause, for both regimens. Among these women, use of conjugated equine estrogens appeared to produce elevations in venous thromboembolism and stroke and a reduction in hip fracture. Estrogen plus progestin results among women who initiated use soon after menopause were similar for venous thromboembolism, stroke, and hip fracture but also included evidence of longer-term elevations in breast cancer, total cancer, and the global index. These analyses provide little support for the hypothesis of favorable effects among women who initiate postmenopausal estrogen use soon after menopause, either for coronary heart disease or for health benefits versus risk indices considered. PMID:19468079

Tuberculosis contact screening and isoniazid preventive therapy in a South Indian district: operational issues for programmatic consideration.

PubMed

Pothukuchi, Madhavi; Nagaraja, Sharath Burugina; Kelamane, Santosha; Satyanarayana, Srinath; Shashidhar; Babu, Sai; Dewan, Puneet; Wares, Fraser

2011-01-01

Under India's Revised National Tuberculosis Control Programme (RNTCP), all household contacts of sputum smear positive Pulmonary Tuberculosis (PTB) patients are screened for TB. In the absence of active TB disease, household contacts aged <6 years are eligible for Isoniazid Preventive Therapy (IPT) (5 milligrams/kilogram body weight/day) for 6 months. To estimate the number of household contacts aged <6 years, of sputum smear positive PTB patients registered for treatment under RNTCP from April to June'2008 in Krishna District, to assess the extent to which they are screened for TB disease and in its absence initiated on IPT. A cross sectional study was conducted. Households of all smear positive PTB cases (n = 848) registered for treatment from April to June'2008 were included. Data on the number of household contacts aged <6 years, the extent to which they were screened for TB disease, and the status of initiation of IPT, was collected. Households of 825 (97%) patients were visited, and 172 household contacts aged <6 years were identified. Of them, 116 (67%) were evaluated for TB disease; none were found to be TB diseased and 97 (84%) contacts were initiated on IPT and 19 (16%) contacts were not initiated on IPT due to shortage of INH tablets in peripheral health centers. The reasons for non-evaluation of the remaining eligible children (n = 56, 33%) include no home visit by the health staff in 25 contacts, home visit done but not evaluated in 31 contacts. House-hold contacts in rural areas were less likely to be evaluated and initiated on IPT [risk ratio 6.65 (95% CI; 3.06-14.42)]. Contact screening and IPT implementation under routine programmatic conditions is sub-optimal. There is an urgent need to sensitize all concerned programme staff on its importance and establishment of mechanisms for rigorous monitoring.

[Fever and petechial exanthema in children].

PubMed

Soult Rubio, J A; Navarro González, J; Olano Claret, P

1992-11-01

In an attempt to determine clinical and analytical predictive parameters of a possible grave disease, we have carried out a retrospective study of 172 children admitted to our hospital with fever and petechiae as initial symptoms. The ages ranged between 1 month and 10 years. Even though we have not found a clinical symptom or analysis sufficiently sensitive as to predict all grave diseases, the general clinical state of the child associated with either a high or low white cell count and an abnormal coagulation study should be alert signals for a serious infectious disease. On the contrary, if the clinical and analytical parameters are within normal limits the risk of a grave disease is low. We emphasize the high incidence of meningococcal disease (26%).

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.

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.

Impact of 6-month earlier versus postponed initiation of rotigotine on long-term outcome: post hoc analysis of patients with early Parkinson's disease with mild symptom severity.

PubMed

Timmermann, Lars; Asgharnejad, Mahnaz; Boroojerdi, Babak; Dohin, Elisabeth; Woltering, Franz; Elmer, Lawrence W

2015-01-01

Investigate impact of 6-month earlier versus postponed initiation of rotigotine in patients with early Parkinson's disease (PD) with mild symptom severity. Long-term benefit of rotigotine in early-PD has been demonstrated: SP702 (NCT00594165) and SP716 (NCT00599196) were long-term, open-label extensions of double-blind, placebo-controlled studies of 6-month maintenance; rotigotine was well tolerated for up to 6 years, and demonstrated efficacy (Unified Parkinson's Disease Rating Scale [UPDRS] II + III below baseline) for ∼ 2 years (SP702) and ∼ 4 years (SP716). Post hoc analysis of patients at Hoehn and Yahr 1-2; groups defined by treatment received in 6-month double-blind studies: 'Rotigotine-Rotigotine' received rotigotine (n = 221), 'Placebo-Rotigotine' received placebo (n = 125). At the start of open-label rotigotine maintenance, UPDRS II + III mean ± SD change from double-blind baseline was: -8.5 ± 10.6 'Rotigotine-Rotigotine', -7.7 ± 9.0 'Placebo-Rotigotine.' After this initial improvement scores gradually increased: It took ∼ 45 months for mean scores to cross baseline in 'Rotigotine-Rotigotine', and ∼ 21 months in 'Placebo-Rotigotine.' At the time mean UPDRS II + III had crossed baseline in 'Placebo-Rotigotine' (open-label week 84; ∼ 21 months), treatment difference (LS-mean) to 'Rotigotine-Rotigotine' change from baseline was -3.89 (95% CI -6.94, -0.84); p = 0.013. In this post hoc analysis, 6-month earlier initiation of rotigotine resulted in slower return to baseline mean UPDRS II + III; initiation of rotigotine in patients with minimal/no functional disability or impairment may lead to an extended benefit.

Mast Cells and Innate Lymphoid Cells: Underappreciated Players in CNS Autoimmune Demyelinating Disease.

PubMed

Brown, Melissa A; Weinberg, Rebecca B

2018-01-01

Multiple sclerosis (MS) and its mouse model, experimental autoimmune encephalomyelitis, are autoimmune CNS inflammatory diseases. As a result of a breakdown in the relatively impermeable blood-brain barrier (BBB) in affected individuals, myelin-specific CD4 + and CD8 + T cells gain entry into the immune privileged CNS and initiate myelin, oligodendrocyte, and nerve axon destruction. However, despite the absolute requirement for T cells, there is increasing evidence that innate immune cells also play critical amplifying roles in disease pathogenesis. By modulating the character and magnitude of the myelin-reactive T cell response and regulating BBB integrity, innate cells affect both disease initiation and progression. Two classes of innate cells, mast cells and innate lymphoid cells (ILCs), have been best studied in models of allergic and gastrointestinal inflammatory diseases. Yet, there is emerging evidence that these cell types also exert a profound influence in CNS inflammatory disease. Both cell types are residents within the meninges and can be activated early in disease to express a wide variety of disease-modifying cytokines and chemokines. In this review, we discuss how mast cells and ILCs can have either disease-promoting or -protecting effects on MS and other CNS inflammatory diseases and how sex hormones may influence this outcome. These observations suggest that targeting these cells and their unique mediators can be exploited therapeutically.

Fish can get diseases too

USGS Publications Warehouse

Winton, J.R.; Mesa, M.; Kurath, G.; Elliot, D.

2005-01-01

Infectious diseases are increasingly recognized as an important component of the ecology of fish in the wild. Many of the viral, bacterial, protozoan and fungal pathogens of fish that were initially discovered in captive fish have their origin among wild populations; however, the impact of disease among these free-ranging stocks has been difficult to study. At the WFRC, combinations of field and laboratory investigations, aided by the tools of molecular biology, have begun to provide information on the ecology of infectious diseases among natural populations of fish in both freshwater and marine ecosystems.

A Naval Postgraduate Dental School Analysis Of Initial Endodontic Treatment

DTIC Science & Technology

2015-07-01

available for consideration as a study pmiicipant. Exclusion Criteria: Patients whose record did not include a final treatment radiograph or whose...of symptoms, tooth type (single versus multi-root), and existing medical conditions (smoker, coronary heart disease , diabetes). lntraoperative...A NAVAL POSTGRADUATE DENT AL SCHOOL ANALYSIS OF INITIAL ENDODONTIC TREATMENT by Allen Daniel Rasmussen, D.M.D. Lieutenant Commander, Dental Corps

Medical Services at an International Summer Camp Event Under Hot and Humid Conditions: Experiences From the 23rd World Scout Jamboree, Japan.

PubMed

Watanabe, Takemasa; Mizutani, Keiji; Iwai, Toshiyasu; Nakashima, Hiroshi

2018-06-01

The 23rd World Scout Jamboree (WSJ) was a 10-day summer camp held in Japan in 2015 under hot and humid conditions. The attendees comprised 33,628 people from 155 countries and territories. The aim of this study was to examine the provision of medical services under such conditions and to identify preventive factors for major diseases among long-term campers. Data were obtained from WSJ medical center records and examined to clarify the effects of age, sex, and period on visit frequencies and rates. Medical records from 3215 patients were examined. Daytime temperatures were 31.5±3.2°C and relative humidity was 61±13% (mean±SD). The initial visit rates among scouts and adults were 72.2 and 77.2 per 1000 persons, respectively. No significant age difference was observed in the initial visit rate; however, it was significantly higher among female patients than male patients. Significant differences were also seen in the adjusted odds ratios by age, sex, and period for disease distributions of initial visit frequencies. In addition, a higher initial visit frequency for heat strain-related diseases was seen among the scouts. Initial visit frequencies for heatstroke and/or dehydration increased just after opening day and persisted until closing day. Our findings suggest the importance of taking effective countermeasures against heat strain, fatigue, and unsanitary conditions at the WSJ. Medical services staff should take attendees' age, sex, and period into consideration to prevent heat strain-related diseases during such camps under hot and humid conditions. Copyright © 2018 Wilderness Medical Society. Published by Elsevier Inc. All rights reserved.

Timing of Radiation Therapy and Chemotherapy After Breast-Conserving Surgery for Node-Positive Breast Cancer: Long-Term Results From International Breast Cancer Study Group Trials VI and VII

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

Karlsson, Per, E-mail: per.karlsson@oncology.gu.se; Cole, Bernard F.; Price, Karen N.

Purpose: To update the previous report from 2 randomized clinical trials, now with a median follow-up of 16 years, to analyze the effect of radiation therapy timing on local failure and disease-free survival. Patients and Methods: From July 1986 to April 1993, International Breast Cancer Study Group trial VI randomly assigned 1475 pre-/perimenopausal women with node-positive breast cancer to receive 3 or 6 cycles of initial chemotherapy (CT). International Breast Cancer Study Group trial VII randomly assigned 1212 postmenopausal women with node-positive breast cancer to receive tamoxifen for 5 years, or tamoxifen for 5 years with 3 early cycles of initial CT. Formore » patients who received breast-conserving surgery (BCS), radiation therapy (RT) was delayed until initial CT was completed; 4 or 7 months after BCS for trial VI and 2 or 4 months for trial VII. We compared RT timing groups among 433 patients on trial VI and 285 patients on trial VII who received BCS plus RT. Endpoints were local failure, regional/distant failure, and disease-free survival (DFS). Results: Among pre-/perimenopausal patients there were no significant differences in disease-related outcomes. The 15-year DFS was 48.2% in the group allocated 3 months initial CT and 44.9% in the group allocated 6 months initial CT (hazard ratio [HR] 1.12; 95% confidence interval [CI] 0.87-1.45). Among postmenopausal patients, the 15-year DFS was 46.1% in the no-initial-CT group and 43.3% in the group allocated 3 months initial CT (HR 1.11; 95% CI 0.82-1.51). Corresponding HRs for local failures were 0.94 (95% CI 0.61-1.46) in trial VI and 1.51 (95% CI 0.77-2.97) in trial VII. For regional/distant failures, the respective HRs were 1.15 (95% CI 0.80-1.63) and 1.08 (95% CI 0.69-1.68). Conclusions: This study confirms that, after more than 15 years of follow-up, it is reasonable to delay radiation therapy until after the completion of standard CT.« less

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.

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…

Association of O-Antigen Serotype with the Magnitude of Initial Systemic Cytokine Responses and Persistence in the Urinary Tract.

PubMed

Horvath, Dennis J; Patel, Ashay S; Mohamed, Ahmad; Storm, Douglas W; Singh, Chandra; Li, Birong; Zhang, Jingwen; Koff, Stephen A; Jayanthi, Venkata R; Mason, Kevin M; Justice, Sheryl S

2016-01-11

Urinary tract infection (UTI) is one of the most common ailments requiring both short-term and prophylactic antibiotic therapies. Progression of infection from the bladder to the kidney is associated with more severe clinical symptoms (e.g., fever and vomiting) as well as with dangerous disease sequelae (e.g., renal scaring and sepsis). Host-pathogen interactions that promote bacterial ascent to the kidney are not completely understood. Prior studies indicate that the magnitude of proinflammatory cytokine elicitation in vitro by clinical isolates of uropathogenic Escherichia coli (UPEC) inversely correlates with the severity of clinical disease. Therefore, we hypothesize that the magnitude of initial proinflammatory responses during infection defines the course and severity of disease. Clinical UPEC isolates obtained from patients with a nonfebrile UTI elicited high systemic proinflammatory responses early during experimental UTI in a murine model and were attenuated in bladder and kidney persistence. Conversely, UPEC isolates obtained from patients with febrile UTI elicited low systemic proinflammatory responses early during experimental UTI and exhibited prolonged persistence in the bladder and kidney. Soluble factors in the supernatant from saturated cultures as well as the lipopolysaccharide (LPS) serotype correlated with the magnitude of proinflammatory responses in vitro. Our data suggest that the structure of the O-antigen sugar moiety of the LPS may determine the strength of cytokine induction by epithelial cells. Moreover, the course and severity of disease appear to be the consequence of the magnitude of initial cytokines produced by the bladder epithelium during infection. The specific host-pathogen interactions that determine the extent and course of disease are not completely understood. Our studies demonstrate that modest changes in the magnitude of cytokine production observed using in vitro models of infection translate into significant ramifications for bacterial persistence and disease severity. While many studies have demonstrated that modifications of the LPS lipid A moiety modulate the extent of Toll-like receptor 4 (TLR4) activation, our studies implicate the O-antigen sugar moiety as another potential rheostat for the modulation of proinflammatory cytokine production. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Association of O-Antigen Serotype with the Magnitude of Initial Systemic Cytokine Responses and Persistence in the Urinary Tract

PubMed Central

Horvath, Dennis J.; Patel, Ashay S.; Mohamed, Ahmad; Storm, Douglas W.; Singh, Chandra; Li, Birong; Zhang, Jingwen; Koff, Stephen A.; Jayanthi, Venkata R.; Mason, Kevin M.

2016-01-01

ABSTRACT Urinary tract infection (UTI) is one of the most common ailments requiring both short-term and prophylactic antibiotic therapies. Progression of infection from the bladder to the kidney is associated with more severe clinical symptoms (e.g., fever and vomiting) as well as with dangerous disease sequelae (e.g., renal scaring and sepsis). Host-pathogen interactions that promote bacterial ascent to the kidney are not completely understood. Prior studies indicate that the magnitude of proinflammatory cytokine elicitation in vitro by clinical isolates of uropathogenic Escherichia coli (UPEC) inversely correlates with the severity of clinical disease. Therefore, we hypothesize that the magnitude of initial proinflammatory responses during infection defines the course and severity of disease. Clinical UPEC isolates obtained from patients with a nonfebrile UTI elicited high systemic proinflammatory responses early during experimental UTI in a murine model and were attenuated in bladder and kidney persistence. Conversely, UPEC isolates obtained from patients with febrile UTI elicited low systemic proinflammatory responses early during experimental UTI and exhibited prolonged persistence in the bladder and kidney. Soluble factors in the supernatant from saturated cultures as well as the lipopolysaccharide (LPS) serotype correlated with the magnitude of proinflammatory responses in vitro. Our data suggest that the structure of the O-antigen sugar moiety of the LPS may determine the strength of cytokine induction by epithelial cells. Moreover, the course and severity of disease appear to be the consequence of the magnitude of initial cytokines produced by the bladder epithelium during infection. IMPORTANCE The specific host-pathogen interactions that determine the extent and course of disease are not completely understood. Our studies demonstrate that modest changes in the magnitude of cytokine production observed using in vitro models of infection translate into significant ramifications for bacterial persistence and disease severity. While many studies have demonstrated that modifications of the LPS lipid A moiety modulate the extent of Toll-like receptor 4 (TLR4) activation, our studies implicate the O-antigen sugar moiety as another potential rheostat for the modulation of proinflammatory cytokine production. PMID:26755631

Gluten Introduction, Breastfeeding, and Celiac Disease: Back to the Drawing Board.

PubMed

Lebwohl, Benjamin; Murray, Joseph A; Verdú, Elena F; Crowe, Sheila E; Dennis, Melinda; Fasano, Alessio; Green, Peter H R; Guandalini, Stefano; Khosla, Chaitan

2016-01-01

This commentary by the leadership of the North American Society for the Study of Celiac Disease (NASSCD) concerns recent research findings regarding infant feeding practices. Celiac disease has increased markedly in recent decades, and seroprevalence studies indicate that this is a true rise, rather than one due to increased awareness and testing. Prior studies have suggested that infant feeding practices and timing of initial gluten exposure are central to the development of celiac disease. Two recent multicenter randomized trials tested strategies of early or delayed gluten introduction in infants, and neither strategy appeared to influence celiac disease risk. These studies also found that breastfeeding did not protect against the development of celiac disease. While disappointing, these results should spur the study of wider environmental risk factors beyond infant feeding, such as intrauterine and perinatal exposures as well as environmental influences later in life, including drug exposure, microbial infections, and the microbiome. Given that celiac disease can develop at any age, it is imperative to study these proposed triggers so as to elucidate the loss of tolerance to gluten and to develop future intervention strategies.

Ethnicity and the first diagnosis of a wide range of cardiovascular diseases: Associations in a linked electronic health record cohort of 1 million patients.

PubMed

George, Julie; Mathur, Rohini; Shah, Anoop Dinesh; Pujades-Rodriguez, Mar; Denaxas, Spiros; Smeeth, Liam; Timmis, Adam; Hemingway, Harry

2017-01-01

While the association of ethnic group with individual cardiovascular diseases has been studied, little is known about ethnic differences in the initial lifetime presentation of clinical cardiovascular disease in contemporary populations. We studied 1,068,318 people, aged ≥30 years and free from diagnosed CVD at baseline (90.9% White, 3.6% South Asian and 2.9% Black), using English linked electronic health records covering primary care, hospital admissions, acute coronary syndrome registry and mortality registry (CALIBER platform). During 5.7 years median follow-up between 1997-2010, 95,224 people experienced an incident cardiovascular diagnosis. 69.9% (67.2%-72.4%) of initial presentation in South Asian <60 yrs were coronary heart disease presentations compared to 47.8% (47.3%-48.3%) in White and 40.1% (36.3%-43.9%) in Black patients. Compared to White patients, Black patients had significantly lower age-sex adjusted hazard ratios (HRs) for initial lifetime presentation of all the coronary disease diagnoses (stable angina HR 0.80 (95% CI 0.68-0.93); unstable angina- 0.75 (0.59-0.97); myocardial infarction 0.49 (0.40-0.62)) while South Asian patients had significantly higher HRs (stable angina- 1.67 (1.52-1.84); unstable angina 1.82 (1.56-2.13); myocardial infarction- 1.67 (1.49-1.87). We found no ethnic differences in initial presentation with heart failure (Black 0.97 (0.79-1.20); S Asian 1.04(0.87-1.26)). Compared to White patients, Black patients were more likely to present with ischaemic stroke (1.24 (0.97-1.58)) and intracerebral haemorrhage (1.44 (0.97-2.12)). Presentation with peripheral arterial disease was less likely for Black (0.63 (0.50-0.80)) and South Asian patients (0.70 (0.57-0.86)) compared with White patients. While we found the anticipated substantial predominance of coronary heart disease presentations in South Asian and predominance of stroke presentations in Black patients, we found no ethnic differences in presentation with heart failure. We consider the public health and research implications of our findings. NCT02176174, www.clinicaltrials.gov.

Fabry nephropathy: a review - how can we optimize the management of Fabry nephropathy?

PubMed

Waldek, Stephen; Feriozzi, Sandro

2014-05-06

Fabry disease is a rare, X-linked, lysosomal storage disease caused by mutations in the gene encoding the enzyme alpha-galactosidase A. Complete or partial deficiency in this enzyme leads to intracellular accumulation of globotriaosylceramide (Gb3) and related glycosphingolipids in many cell types throughout the body, including the kidney. Progressive accumulation of Gb3 in podocytes, epithelial cells and the tubular cells of the distal tubule and loop of Henle contribute to the renal symptoms of Fabry disease, which manifest as proteinuria and reduced glomerular filtration rate leading to chronic kidney disease and progression to end-stage renal disease. Early diagnosis and timely initiation of treatment of Fabry renal disease is an important facet of disease management. Initiating treatment with enzyme replacement therapy (ERT; agalsidase alfa, Replagal®, Shire; agalsidase beta, Fabrazyme®, Genzyme) as part of a comprehensive strategy to prevent complications of the disease, may be beneficial in stabilizing renal function or slowing its decline. Early initiation of ERT may also be more effective than initiating therapy in patients with more advanced disease. Several strategies are required to complement the use of ERT and treat the myriad of associated symptoms and organ involvements. In particular, patients with renal Fabry disease are at risk of cardiovascular events, such as high blood pressure, cardiac arrhythmias and stroke. This review discusses the management of renal involvement in Fabry disease, including diagnosis, treatments, and follow-up, and explores recent advances in the use of biomarkers to assist with diagnosis, monitoring disease progression and response to treatment.

Fabry nephropathy: a review – how can we optimize the management of Fabry nephropathy?

PubMed Central

2014-01-01

Fabry disease is a rare, X-linked, lysosomal storage disease caused by mutations in the gene encoding the enzyme alpha-galactosidase A. Complete or partial deficiency in this enzyme leads to intracellular accumulation of globotriaosylceramide (Gb3) and related glycosphingolipids in many cell types throughout the body, including the kidney. Progressive accumulation of Gb3 in podocytes, epithelial cells and the tubular cells of the distal tubule and loop of Henle contribute to the renal symptoms of Fabry disease, which manifest as proteinuria and reduced glomerular filtration rate leading to chronic kidney disease and progression to end-stage renal disease. Early diagnosis and timely initiation of treatment of Fabry renal disease is an important facet of disease management. Initiating treatment with enzyme replacement therapy (ERT; agalsidase alfa, Replagal®, Shire; agalsidase beta, Fabrazyme®, Genzyme) as part of a comprehensive strategy to prevent complications of the disease, may be beneficial in stabilizing renal function or slowing its decline. Early initiation of ERT may also be more effective than initiating therapy in patients with more advanced disease. Several strategies are required to complement the use of ERT and treat the myriad of associated symptoms and organ involvements. In particular, patients with renal Fabry disease are at risk of cardiovascular events, such as high blood pressure, cardiac arrhythmias and stroke. This review discusses the management of renal involvement in Fabry disease, including diagnosis, treatments, and follow-up, and explores recent advances in the use of biomarkers to assist with diagnosis, monitoring disease progression and response to treatment. PMID:24886109

Patterns and Timing of Failure for Diffuse Large B-Cell Lymphoma After Initial Therapy in a Cohort Who Underwent Autologous Bone Marrow Transplantation for Relapse

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

Dhakal, Sughosh; Bates, James E.; Casulo, Carla

Purpose: To evaluate the location and timing of initial recurrence in patients with diffuse large B-cell lymphoma (DLBCL) who subsequently underwent high-dose chemotherapy with autologous stem cell transplant (HDC/ASCT), to direct approaches for disease surveillance, elucidate the patterns of failure of contemporary treatment strategies, and guide adjuvant treatment decisions. Methods and Materials: We analyzed consecutive patients with DLBCL who underwent HDC/ASCT between May 1992 and March 2014 at our institution. Of the 187 evaluable patients, 8 had incomplete data, and 79 underwent HDC/ASCT as a component of initial treatment for de novo or refractory DLBCL and were excluded from furthermore » analysis. Results: The median age was 50.8 years; the median time to relapse was 1.3 years. Patients were segregated according to the initial stage at diagnosis, with early stage (ES) defined as stage I/II and advanced stage (AS) defined as stage III/IV. In total, 40.4% of the ES and 75.5% of the AS patients relapsed in sites of initial disease; 68.4% of those with ES disease and 75.0% of those with AS disease relapsed in sites of initial disease only. Extranodal relapses were common (44.7% in ES and 35.9% in AS) and occurred in a variety of organs, although gastrointestinal tract/liver (n=12) was most frequent. Conclusions: Most patients with DLBCL who relapse and subsequently undergo HDC/ASCT initially recur in the previously involved disease site(s). Time to recurrence is brief, suggesting that frequency of screening is most justifiably greatest in the early posttherapy years. © 2016 Elsevier Inc.« less

View of God as benevolent and forgiving or punishing and judgmental predicts HIV disease progression.

PubMed

Ironson, Gail; Stuetzle, Rick; Ironson, Dale; Balbin, Elizabeth; Kremer, Heidemarie; George, Annie; Schneiderman, Neil; Fletcher, Mary Ann

2011-12-01

This study assessed the predictive relationship between View of God beliefs and change in CD4-cell and Viral Load (VL) in HIV positive people over an extended period. A diverse sample of HIVseropositive participants (N = 101) undergoing comprehensive psychological assessment and blood draws over the course of 4 years completed the View of God Inventory with subscales measuring Positive View (benevolent/forgiving) and Negative View of God (harsh/judgmental/punishing). Adjusting for initial disease status, age, gender, ethnicity, education, and antiretroviral medication (at every 6-month visit), a Positive View of God predicted significantly slower disease-progression (better preservation of CD4-cells, better control of VL), whereas a Negative View of God predicted faster disease-progression over 4 years. Effect sizes were greater than those previously demonstrated for psychosocial variables known to predict HIV-disease-progression, such as depression and coping. Results remained significant even after adjusting for church attendance and psychosocial variables (health behaviors, mood, and coping). These results provide good initial evidence that spiritual beliefs may predict health outcomes.

The Sleep Disorder in Anti-lgLON5 Disease.

PubMed

Gaig, Carles; Iranzo, Alex; Santamaria, Joan; Graus, Francesc

2018-05-23

To review the clinical and polysomnographic features of the sleep disorder occurring in the recently described anti-IgLON5 disease. The hallmark of the disease is the presence of antibodies against IgLON5, a neural cell adhesion molecule of unknown function. The disease presents a robust HLA association, and the neuropathological examination shows a novel neuronal tauopathy with predominant hypothalamic and brainstem involvement. Most patients (> 80%) present sleep-related vocalizations with movements and behaviors and sleep-disordered breathing. Polysomnographic studies show (1) a complex NREM sleep parasomnia at sleep initiation characterized by undifferentiated NREM or poorly structured N2 sleep with sleep-talking or mumbling, and simple or finalistic movements followed by normal periods of N3 or N2 NREM sleep, (2) REM sleep behavior disorder (RBD), and (3) obstructive sleep apnea with stridor. The last two features appear mainly in periods where NREM sleep normalizes. Identification of the anti-IgLON5 sleep disorder is important to suspect the disease. The combination of abnormal NREM sleep initiation, followed by normal periods of NREM sleep and RBD, represents a novel parasomnia.

The limitations of opportunistic epidemiology, pseudopod epidemiology.

PubMed

Kuller, Lewis H

2016-10-01

Epidemiology has been remarkably successful in the past in identifying the important agents of disease, the impact of the environment, both physical and social, and interrelationship with host susceptibility (genomics). Many of the advances in improving the health of individuals and populations have been the result of epidemiology studies that have identified the specific "agents" of disease and application of public health and preventive medicine. In recent years, large longitudinal studies have dominated epidemiology research, especially long incubation period chronic diseases. The initial hypotheses in these studies have been expanded by vertical extension studies using newer technologies to measure independent variables, vertical pseudopods, and additional studies of other diseases, horizontal pseudopods, of the original longitudinal study. Host susceptibility, i.e. genomics, has also become a prominent component of these longitudinal studies. The critical question addressed in this paper is whether these "pseudopod" epidemiology approaches have enhanced public health or generated a large number of studies of little impact.

Active Case Finding for Communicable Diseases in Prison Settings: Increasing Testing Coverage and Uptake Among the Prison Population in the European Union/European Economic Area

PubMed Central

Vroling, Hilde; Babudieri, Sergio; Monarca, Roberto; Vonk Noordegraaf-Schouten, Marije; Beer, Netta; Gomes Dias, Joana; O’Moore, Éamonn; Hedrich, Dagmar; Oordt-Speets, Anouk

2018-01-01

Abstract Prison populations are disproportionally affected by communicable diseases when compared with the general community because of a complex mix of socioeconomic determinants and environmental factors. Tailored and adequate health care provision in prisons has the potential to reach vulnerable and underserved groups and address their complex needs. We investigated the available evidence on modalities and effectiveness of active case-finding interventions in prisons by searching PubMed, Embase, and the Cochrane Library for records on prison and active case finding with no language limit. Conference abstracts and unpublished research reports also were retrieved. We analyzed the findings by testing modality, outcomes, and study quality. The included 90 records—63 peer-reviewed, 26 from gray literature, and 1 systematic review—reported variously on viral hepatitis, human immunodeficiency virus, sexually transmitted infections, and tuberculosis. No records were retrieved for other communicable diseases. Provider-initiated opt-in testing was the most frequently investigated modality. Testing at entry and provider-initiated testing were reported to result in comparatively higher uptake ranges. However, no comparative studies were identified that reported statistically significant differences between testing modalities. Positivity rates among tested inmates ranged broadly but were generally high for all diseases. The evidence on active case finding in correctional facilities is limited, heterogeneous, and of low quality, making it challenging to draw conclusions on the effect of different testing modalities. Scale-up of provider-initiated testing in European correctional facilities could substantially reduce the undiagnosed fraction and, hence, prevent additional disease transmission in both prison settings and the community at large. PMID:29648594

Remission of Grave's disease after oral anti-thyroid drug treatment.

PubMed

Ishtiaq, Osama; Waseem, Sabiha; Haque, M Naeemul; Islam, Najmul; Jabbar, Abdul

2009-11-01

To evaluate remission rate of anti-thyroid drug treatment in patients with Grave's disease, and to study the factors associated with remission. A cross sectional study. The Endocrine Department of the Aga Khan University Hospital, Karachi from 1999 to 2000. Seventy four patients of Grave's disease were recruited who were prescribed medical treatment. Grave's disease was diagnosed in the presence of clinical and biochemical hyperthyroidism along with anti-microsomal (AMA) and anti-thyroglobulin antibodies (ATA) and thyroid scan. These patients were prescribed oral anti-thyroid drugs using titration regime and followed at 3, 6, 12 and 18 months. Patients were categorized into two groups: "remission group" and "treatment failure group" and results were compared using a chi-square test, t-test and logistic regression model with significance at p < 0.05. A majority of the patients were females (62.6%, n=46). During the follow-up period of 18 months, 41.9% patients went into remission. Univariate analysis showed that the initial free T4 level was significantly different (p < 0.05) in patients in remission and treatment failure groups. Multivariate analysis showed only initial free T4 level was a significant predictor of outcome. Positive AMA patients (n=27) had higher treatment failure (odds ratio: 2.55: 95%, CI 0.69 - 9:31), although the difference was not statistically significant (p = 0.13). Remission rates with oral anti-thyroid agents is markedly high. Patients should be offered alternate treatment options to those who do not enter remission during a period of 12-18 months of treatment, those who develop relapse, and those who have aggressive disease on initial presentation.

Gut Microbiome Function Predicts Response to Anti-integrin Biologic Therapy in Inflammatory Bowel Diseases.

PubMed

Ananthakrishnan, Ashwin N; Luo, Chengwei; Yajnik, Vijay; Khalili, Hamed; Garber, John J; Stevens, Betsy W; Cleland, Thomas; Xavier, Ramnik J

2017-05-10

The gut microbiome plays a central role in inflammatory bowel diseases (IBDs) pathogenesis and propagation. To determine whether the gut microbiome may predict responses to IBD therapy, we conducted a prospective study with Crohn's disease (CD) or ulcerative colitis (UC) patients initiating anti-integrin therapy (vedolizumab). Disease activity and stool metagenomes at baseline, and weeks 14, 30, and 54 after therapy initiation were assessed. Community α-diversity was significantly higher, and Roseburia inulinivorans and a Burkholderiales species were more abundant at baseline among CD patients achieving week 14 remission. Several significant associations were identified with microbial function; 13 pathways including branched chain amino acid synthesis were significantly enriched in baseline samples from CD patients achieving remission. A neural network algorithm, vedoNet, incorporating microbiome and clinical data, provided highest classifying power for clinical remission. We hypothesize that the trajectory of early microbiome changes may be a marker of response to IBD treatment. Copyright © 2017 Elsevier Inc. All rights reserved.

Meningeal mast cells affect early T cell central nervous system infiltration and blood-brain barrier integrity through TNF: a role for neutrophil recruitment?

PubMed

Sayed, Blayne A; Christy, Alison L; Walker, Margaret E; Brown, Melissa A

2010-06-15

Mast cells contribute to the pathogenesis of experimental autoimmune encephalomyelitis, a rodent model of the human demyelinating disease multiple sclerosis. Yet their site and mode of action is unknown. In both diseases, myelin-specific T cells are initially activated in peripheral lymphoid organs. However, for disease to occur, these cells must enter the immunologically privileged CNS through a breach in the relatively impermeable blood-brain barrier. In this study, we demonstrate that a dense population of resident mast cells in the meninges, structures surrounding the brain and spinal cord, regulate basal CNS barrier function, facilitating initial T cell CNS entry. Through the expression of TNF, mast cells recruit an early wave of neutrophils to the CNS. We propose that neutrophils in turn promote the blood-brain barrier breach and together with T cells lead to further inflammatory cell influx and myelin damage. These findings provide specific targets for intervention in multiple sclerosis as well as other immune-mediated CNS diseases.

Combining medical informatics and bioinformatics toward tools for personalized medicine.

PubMed

Sarachan, B D; Simmons, M K; Subramanian, P; Temkin, J M

2003-01-01

Key bioinformatics and medical informatics research areas need to be identified to advance knowledge and understanding of disease risk factors and molecular disease pathology in the 21 st century toward new diagnoses, prognoses, and treatments. Three high-impact informatics areas are identified: predictive medicine (to identify significant correlations within clinical data using statistical and artificial intelligence methods), along with pathway informatics and cellular simulations (that combine biological knowledge with advanced informatics to elucidate molecular disease pathology). Initial predictive models have been developed for a pilot study in Huntington's disease. An initial bioinformatics platform has been developed for the reconstruction and analysis of pathways, and work has begun on pathway simulation. A bioinformatics research program has been established at GE Global Research Center as an important technology toward next generation medical diagnostics. We anticipate that 21 st century medical research will be a combination of informatics tools with traditional biology wet lab research, and that this will translate to increased use of informatics techniques in the clinic.

The First Endoscopy in Suspected Inflammatory Bowel Disease.

PubMed

Fausel, Rebecca A; Kornbluth, Asher; Dubinsky, Marla C

2016-10-01

In a patient presenting with suspected inflammatory bowel disease, the initial endoscopic evaluation is a valuable tool for determining the correct disease diagnosis and the extent and severity of disease. A full colonoscopy and ileoscopy should be performed when possible, with systematic biopsies from each segment. When a diagnosis of inflammatory bowel disease is established, it is possible to distinguish between Crohn disease and ulcerative colitis, and specific endoscopic features may assist in this categorization. Because patchy healing can occur with treatment, it is important to obtain a thorough and accurate assessment of disease characteristics and distribution before initiating therapy. Copyright © 2016 Elsevier Inc. All rights reserved.

Looking into the future: Using induced pluripotent stem cells to build two and three dimensional ocular tissue for cell therapy and disease modeling.

PubMed

Song, Min Jae; Bharti, Kapil

2016-05-01

Retinal degenerative diseases are the leading cause of irreversible vision loss in developed countries. In many cases the diseases originate in the homeostatic unit in the back of the eye that contains the retina, retinal pigment epithelium (RPE) and the choriocapillaris. RPE is a central and a critical component of this homeostatic unit, maintaining photoreceptor function and survival on the apical side and choriocapillaris health on the basal side. In diseases like age-related macular degeneration (AMD), it is thought that RPE dysfunctions cause disease-initiating events and as the RPE degenerates photoreceptors begin to die and patients start loosing vision. Patient-specific induced pluripotent stem (iPS) cell-derived RPE provides direct access to a patient's genetics and allow the possibility of identifying the initiating events of RPE-associated degenerative diseases. Furthermore, iPS cell-derived RPE cells are being tested as a potential cell replacement in disease stages with RPE atrophy. In this article we summarize the recent progress in the field of iPS cell-derived RPE "disease modeling" and cell therapies and also discuss the possibilities of developing a model of the entire homeostatic unit to aid in studying disease processes in the future. This article is part of a Special Issue entitled SI: PSC and the brain. Published by Elsevier B.V.

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).

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.

Incidence of chronic obstructive pulmonary disease based on three spirometric diagnostic criteria in Sao Paulo, Brazil: a nine-year follow-up since the PLATINO prevalence study.

PubMed

Moreira, Graciane Laender; Gazzotti, Mariana Rodrigues; Manzano, Beatriz Martins; Nascimento, Oliver; Perez-Padilla, Rogelio; Menezes, Ana Maria Baptista; Jardim, José Roberto

2015-01-01

Chronic obstructive pulmonary disease (COPD) is a respiratory disease of high prevalence and socioeconomic impact worldwide. It affects approximately 16% of the population of São Paulo. The incidence of COPD is still unknown in Brazil. The aim of this study was to estimate new cases of COPD in a population-based sample in São Paulo, Brazil, using three different spirometric diagnostic criteria, and to assess the concordance between these criteria. Prospective cohort study, in the city of São Paulo, Brazil. A questionnaire was applied and anthropometry and pre and post-bronchodilator spirometry were performed on the same subjects as in the initial PLATINO study (2003) in São Paulo. Data from this follow-up study were added to the original database of the initial phase. Incident COPD cases refer to subjects who developed the disease in accordance with each spirometric criterion during the nine-year follow-up period. The Statistical Package for the Social Sciences, version 17.0 (SPSS Inc., Chicago, IL, USA) was used in the analysis and the significance level was set at P < 0.05. 613 subjects participated in the follow-up. New COPD cases ranged in frequency from 1.4% to 4.0%, depending on the diagnostic criterion used. The concordance between the criteria ranged from 35% to 60%. The incidence of COPD after a nine-year follow-up was high, but varied according to the spirometric criterion used. The agreement between the criteria for identifying new cases of the disease ranged from 35% to 60%.

78 FR 8152 - Proposed Collection; Comment Request: Women's Health Initiative Observational Study

Federal Register 2010, 2011, 2012, 2013, 2014

2013-02-05

... of Management and Budget (OMB) for review and approval. Proposed Collection: Title: The Women's... women and relating subsequent disease development to baseline assessments of historical, physical...

78 FR 6329 - Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Initial Review

Federal Register 2010, 2011, 2012, 2013, 2014

2013-01-30

... announced below concerns Birth Defects Study to Evaluate Pregnancy exposureS (BD-STEPS), FOA DD13-003... evaluation of applications received in response to ``Birth Defects Study to Evaluate Pregnancy exposureS (BD...

Changes in expression of T-helper (Th) 1- and Th2-associated chemokine receptors on peripheral blood lymphocytes and plasma concentrations of their ligands, interferon-inducible protein-10 and thymus and activation-regulated chemokine, after antithyroid drug administration in hyperthyroid patients with Graves' disease.

PubMed

Inukai, Yoshihisa; Momobayashi, Atsushi; Sugawara, Naoto; Aso, Yoshimasa

2007-06-01

Although Graves' disease is considered an autoantibody-mediated, T-helper 2 (Th2)-dominant disease, Th1-dominance may prevail in its initial phase. We longitudinally investigated Th1/Th2 balance in untreated hyperthyroid patients with Graves' disease after treatment of methimazole (MMI), an antithyroid drug. University clinic outpatients were studied prospectively. Subjects included 23 untreated hyperthyroid patients with Graves' disease and 17 age-matched control subjects. Before and after treatment, we measured Th1- and Th2-associated chemokine receptors (CXCR)3 and CCR4, on peripheral blood lymphocytes using flow cytometry, as well as plasma concentrations of their ligands, interferon-inducible protein (IP)-10 and thymus and activation-regulated chemokine (TARC). The percentage of CXCR3-expressing cells among CD4+T lymphocytes and plasma IP-10 was significantly higher in hyperthyroid Graves' disease patients than in controls. At 12 and 24 weeks after initiation of MMI, percentage of CXCR3-expressing CD4+T lymphocytes had decreased significantly, while the percentage of CCR4-expressing CD4+T lymphocytes had increased significantly at 24 weeks. The CXCR3/CCR4 ratio had decreased significantly at 24 weeks. Plasma concentrations of IP-10 had decreased significantly at 12 and 24 weeks. Plasma concentrations of TARC also had decreased significantly at 24 weeks. In hyperthyroid patients with Graves' disease in the active phase, Th1 cells rather than Th2 cells predominated among peripheral blood lymphocytes. After initiation of MMI, an ongoing transition from Th1 to Th2 dominance occurred.

Treatment of inflammatory bowel disease: what's new in Digestive Disease Week 2016.

PubMed

Chaparro, María

2016-09-01

Inflammatory bowel disease is a chronic disorder of unknown aetiology that results from a pathologic response from both the innate and acquired immune systems, leading to chronic inflammation of the gastrointestinal tract. New drugs have been introduced into the therapeutic armamentarium of inflammatory bowel disease but are not effective in all patients; moreover, among initial responders, there have been reports of loss of response over time. In addition, these drugs sometimes have adverse effects and are often expensive. The present article reviews the studies presented at Digestive Disease Week 2016 that provided new data on the optimisation of currently approved treatments for inflammatory bowel disease, experience with recently approved drugs in clinical practice, and some studies on molecules that are under development for the treatment of these diseases. Copyright © 2016 Elsevier España, S.L.U. All rights reserved.

Clinical course of thyroid function and thyroid associated-ophthalmopathy in patients with euthyroid Graves' disease.

PubMed

Suzuki, Nami; Noh, Jaeduk Yoshimura; Kameda, Toshiaki; Yoshihara, Ai; Ohye, Hidemi; Suzuki, Miho; Matsumoto, Masako; Kunii, Yo; Iwaku, Kenji; Watanabe, Natsuko; Mukasa, Koji; Kozaki, Ai; Inoue, Toshu; Sugino, Kiminori; Ito, Koichi

2018-01-01

Euthyroid Graves' disease (EGD) is a rare condition defined as the presence of thyroid-associated ophthalmopathy (TAO) in patients with normal thyroid function. Due to the rarity of this disease, only a limited number of studies and case reports are available for further evaluation of the characteristics of the disease. The aim of this study was to examine the changes in the thyroid function, thyrotropin receptor antibodies (TRAb) and eye symptoms, and then determine whether TRAb is related to TAO in EGD patients. TRAb in this study was defined as including both thyrotropin-binding inhibitory immunoglobulin (TBII) and thyroid-stimulating immunoglobulin (TSAb). Medical records of patients diagnosed with EGD were reviewed. Ophthalmologists specializing in TAO examined the eyes of all subjects. Of the 58 patients diagnosed with EGD, 24.1% developed hyperthyroidism, while 3.4% developed hypothyroidism. A total of 72.4% of the 58 patients remained euthyroid throughout the entire follow-up period. At the initial presentation, TBII and TSAb were positive in 74.5% and 70.5%, respectively. Ophthalmic treatments were administered to 30 (51.7%) out of the 58 patients. A significant spontaneous improvement of the eye symptoms was found in 28 of the EGD patients who did not require eye treatments. EGD patients exhibited positive rates for both TBII and TSAb, with the number of the TRAb-positive patients gradually decreasing while the eye symptoms spontaneously improved over time. There were no correlations found between TRAb at initial presentation and the eye symptoms. TBII and TSAb were positive in about 70% of EGD patients at their initial visit. Thyroid functions of EGD patients who have been euthyroid for more than 6.7 years may continue to remain euthyroid in the future.

Effective heart disease prevention: lessons from a qualitative study of user perspectives in Bangladeshi, Indian and Pakistani communities.

PubMed

Netto, G; McCloughan, L; Bhatnagar, A

2007-03-01

Coronary heart disease (CHD) has a high mortality, incidence and prevalence among Indian, Pakistani and Bangladeshi communities in the UK, indicating the need for effective heart disease prevention initiatives for these communities. This paper considers how service user perspectives can be used to develop effective, culturally focused CHD prevention interventions for these target groups by addressing identified barriers, including deeply held cultural beliefs. A qualitative research study, using a longitudinal action research approach. This was a community-based study in Edinburgh. Six focus group discussions--two for each community--were organized with participants from these communities at the beginning of the project. A further six focus group discussions for the same communities were organized six months later. Over the period examined, participants reported varying changes in levels of knowledge relating to the nature, causes and symptoms of CHD. Some participants reported taking slight to significant steps to reduce or prevent heart disease, while others did not. The project was viewed as helpful in increasing knowledge about CHD and preventive measures and encouraging healthier lifestyles. However, persistent barriers to change were also identified, requiring changes to the project that involved not only matching intervention materials and messages to observable, superficial characteristics of the target population, but more fundamental changes that address the cultural, social, historical, environmental and psychological forces that influence health behaviour. CHD prevention initiatives need to identify and respond to deep-rooted influences on health-behaviour in 'at-risk' groups, in addition to superficial characteristics of the target populations. It is important for specific prevention initiatives to be linked into wider CHD frameworks to ensure transferability of learning and integration within wider service provision.

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

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

Practical aspects of recruitment and retention in clinical trials of rare genetic diseases: the phenylketonuria (PKU) experience.

PubMed

DeWard, Stephanie J; Wilson, Ashley; Bausell, Heather; Volz, Ashley S; Mooney, Kimberly

2014-02-01

Bringing treatments for rare genetic diseases to patients requires clinical research. Despite increasing activism from patient support and advocacy groups to increase access to clinical research studies, connecting rare disease patients with the clinical research opportunities that may help them has proven challenging. Chief among these challenges are the low incidence of these diseases resulting in a very small pool of known patients with a particular disease, difficulty of diagnosing rare genetic diseases, logistical issues such as long distances to the nearest treatment center, and substantial disease burden leading to loss of independence. Using clinical studies of phenylketonuria as an example, this paper discusses how, based on the authors' collective experience, partnership among clinicians, patients, study coordinators, genetic counselors, dietitians, industry, patient support groups, and families can help overcome the challenges of recruiting and retaining patients in rare disease clinical trials. We discuss specific methods of collaboration, communication, and education as part of a long-term effort to build a community committed to advancing the medical care of patients with rare genetic diseases. By talking to patients and families regularly about research initiatives and taking steps to make study participation as easy as possible, rare disease clinic staff can help ensure adequate study enrollment and successful study completion.

Consensus Statement of Society of Abdominal Radiology Disease-Focused Panel on Barium Esophagography in Gastroesophageal Reflux Disease.

PubMed

Levine, Marc S; Carucci, Laura R; DiSantis, David J; Einstein, David M; Hawn, Mary T; Martin-Harris, Bonnie; Katzka, David A; Morgan, Desiree E; Rubesin, Stephen E; Scholz, Francis J; Turner, Mary Ann; Wolf, Ellen L; Canon, Cheri L

2016-11-01

The Society of Abdominal Radiology established a panel to prepare a consensus statement on the role of barium esophagography in gastroesophageal reflux disease (GERD), as well as recommended techniques for performing the fluoroscopic examination and the gamut of findings associated with this condition. Because it is an inexpensive, noninvasive, and widely available study that requires no sedation, barium esophagography may be performed as the initial test for GERD or in conjunction with other tests such as endoscopy.

Rare variants and autoimmune disease.

PubMed

Massey, Jonathan; Eyre, Steve

2014-09-01

The study of rare variants in monogenic forms of autoimmune disease has offered insight into the aetiology of more complex pathologies. Research in complex autoimmune disease initially focused on sequencing candidate genes, with some early successes, notably in uncovering low-frequency variation associated with Type 1 diabetes mellitus. However, other early examples have proved difficult to replicate, and a recent study across six autoimmune diseases, re-sequencing 25 autoimmune disease-associated genes in large sample sizes, failed to find any associated rare variants. The study of rare and low-frequency variation in autoimmune diseases has been made accessible by the inclusion of such variants on custom genotyping arrays (e.g. Immunochip and Exome arrays). Whole-exome sequencing approaches are now also being utilised to uncover the contribution of rare coding variants to disease susceptibility, severity and treatment response. Other sequencing strategies are starting to uncover the role of regulatory rare variation. © The Author 2014. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Conservative versus invasive stable ischemic heart disease management strategies: what do we plan to learn from the ISCHEMIA trial?

PubMed

Cheng-Torres, Kathleen A; Desai, Karan P; Sidhu, Mandeep S; Maron, David J; Boden, William E

2016-01-01

Over the past decade, landmark randomized clinical trials comparing initial management strategies in stable ischemic heart disease (SIHD) have demonstrated no significant reduction in 'hard' end points (all-cause mortality, cardiac death or myocardial infarction) with one strategy versus another. The main advantage derived from early revascularization is improved short-term quality of life. Nonetheless, questions remain regarding how best to manage SIHD patients, such as whether a high-risk subgroup can be identified that may experience a survival or myocardial infarction benefit from early revascularization, and if not, when should diagnostic catheterization and revascularization be performed. The International Study of Comparative Health Effectiveness with Medical and Invasive Approaches trial is designed to address these questions by randomizing SIHD patients with at least moderate ischemia to an initial conservative strategy of optimal medical therapy or an initial invasive strategy of optimal medical therapy plus cardiac catheterization and revascularization.

Methodological issues of genetic association studies.

PubMed

Simundic, Ana-Maria

2010-12-01

Genetic association studies explore the association between genetic polymorphisms and a certain trait, disease or predisposition to disease. It has long been acknowledged that many genetic association studies fail to replicate their initial positive findings. This raises concern about the methodological quality of these reports. Case-control genetic association studies often suffer from various methodological flaws in study design and data analysis, and are often reported poorly. Flawed methodology and poor reporting leads to distorted results and incorrect conclusions. Many journals have adopted guidelines for reporting genetic association studies. In this review, some major methodological determinants of genetic association studies will be discussed.

[New therapies for children affected by bone diseases].

PubMed

Ballhausen, Diana; Dépraz, Nuria Garcia; Kern, Ilse; Unger, Sheila; Bonafé, Luisa

2012-02-22

Considerable progress has been achieved in recent years in treating children affected by bone diseases. Advances in the understanding of the molecular pathophysiology of genetic bone diseases have led to the development of enzyme replacement therapies for various lysosomal storage diseases, following the breakthrough initiated in treating Gaucher disease. Clinical studies are underway with tailored molecules correcting bone fragility and alleviating chronic bone pain and other manifestations of hypophosphatasia, or promoting growth of long bones in achondroplasia patients. We further report our very encouraging experience with intravenous bisphosphonate treatment in children suffering from secondary osteopenia and the high prevalence of calcium and vitamin D deficits in these severely disabled children.

The role of nutrition and nutraceutical supplements in the treatment of hypertension

PubMed Central

Houston, Mark

2014-01-01

Vascular biology, endothelial and vascular smooth muscle and cardiac dysfunction play a primary role in the initiation and perpetuation of hypertension, cardiovascular disease and target organ damage. Nutrient-gene interactions and epigenetics are predominant factors in promoting beneficial or detrimental effects in cardiovascular health and hypertension. Macronutrients and micronutrients can prevent, control and treat hypertension through numerous mechanisms related to vascular biology. Oxidative stress, inflammation and autoimmune dysfunction initiate and propagate hypertension and cardiovascular disease. There is a role for the selected use of single and component nutraceutical supplements, vitamins, antioxidants and minerals in the treatment of hypertension based on scientifically controlled studies which complement optimal nutrition, coupled with other lifestyle modifications. PMID:24575172

Efficacy and safety of febuxostat in 73 gouty patients with stage 4/5 chronic kidney disease: A retrospective study of 10 centers.

PubMed

Juge, Pierre-Antoine; Truchetet, Marie-Elise; Pillebout, Evangeline; Ottaviani, Sébastien; Vigneau, Cécile; Loustau, Clotilde; Cornec, Divi; Pascart, Tristan; Snanoudj, Renaud; Bailly, Florian; Cornec-Le Gall, Emilie; Schaeverbeke, Thierry; Saraux, Alain; Dieudé, Philippe; Flipo, René-Marc; Richette, Pascal; Lioté, Frédéric; Bardin, Thomas; Chalès, Gérard; Ea, Hang-Korng

2017-10-01

The allopurinol dose is limited in chronic kidney disease, particularly stage 4/5 chronic kidney disease. Febuxostat has a hepatic metabolism and has been approved without dose adaptation in gouty patients with stage 1-3 chronic kidney disease. We aimed to study the safety and efficacy of febuxostat for stage 4/5 chronic kidney disease. In this retrospective study, we included patients with (1) a diagnosis of gout, (2) febuxostat treatment, (3) estimated glomerular filtration rate≤30mL/min/1.73m 2 (Modification of Diet in Renal Disease formula) at febuxostat initiation and (4) follow-up for at least 3 months after febuxostat initiation. Efficacy, safety and variation in estimated glomerular filtration rate were analyzed. We included 73 patients (mean age 70.2±11.8, 61 men, 31 with vascular chronic kidney disease and 18 renal transplantation) with gout (baseline serum uric acid level=9.86±2.85mg/dL, mean gout duration 6.2±7.0 years) from 10 academic centers. Comorbidities included cardiac failure (17.8%), hypertension (98.6%), diabetes mellitus (30.1%), dyslipidemia (64.8%) and history of cardiovascular events (38.4%). At the last visit (mean follow-up 68.5±64.8 weeks), the daily dose of febuxostat was 40mg for 7 patients (10.5%), 80mg for 50 (74.6%) and 120mg for 10 (14.9%). Serum uric acid level was<6mg/dL for 49 patients (67%). Renal function improved for 18 patients, was unchanged for 24 and worsened for 31; 19 patients experienced flares and 1 patient, limb edema. Febuxostat seemed efficient in gouty patients with stage 4/5 chronic kidney disease. However, safety data were not clear regarding renal function. Larger studies are needed to assess safety. Copyright © 2016 Société française de rhumatologie. Published by Elsevier SAS. All rights reserved.

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

Tick-Borne Pathogen – Reversed and Conventional Discovery of Disease

PubMed Central

Tijsse-Klasen, Ellen; Koopmans, Marion P. G.; Sprong, Hein

2014-01-01

Molecular methods have increased the number of known microorganisms associated with ticks significantly. Some of these newly identified microorganisms are readily linked to human disease while others are yet unknown to cause human disease. The face of tick-borne disease discovery has changed with more diseases now being discovered in a “reversed way,” detecting disease cases only years after the tick-borne microorganism was first discovered. Compared to the conventional discovery of infectious diseases, reverse order discovery presents researchers with new challenges. Estimating public health risks of such agents is especially challenging, as case definitions and diagnostic procedures may initially be missing. We discuss the advantages and shortcomings of molecular methods, serology, and epidemiological studies that might be used to study some fundamental questions regarding newly identified tick-borne diseases. With increased tick-exposure and improved detection methods, more tick-borne microorganisms will be added to the list of pathogens causing disease in humans in the future. PMID:25072045

Serious Fall Injuries Before and After Initiation of Hemodialysis Among Older ESRD Patients in the United States: A Retrospective Cohort Study.

PubMed

Plantinga, Laura C; Patzer, Rachel E; Franch, Harold A; Bowling, C Barrett

2017-07-01

Because initiation of dialysis therapy often occurs in the setting of acute illness and may signal worsening health and functional decline, we examined whether rates of serious fall injuries among older hemodialysis patients differ before and after dialysis therapy initiation. Retrospective cohort study of claims data from the 2 years spanning dialysis therapy initiation among patients initiating dialysis therapy in 2010 to 2012. Claims from 81,653 Medicare end-stage renal disease beneficiaries aged 67 to 100 years. Post- versus pre-dialysis therapy initiation periods, defined as on or after versus before dialysis therapy initiation. Serious fall injuries were defined using diagnostic codes for falls in combination with fractures, brain injuries, or joint dislocation. Incidence rate ratios (overall and stratified) for post- versus pre-dialysis therapy initiation periods were estimated using generalized estimating equation models with a negative binomial link. Overall, 12,757 serious fall injuries occurred in the pre- and post-dialysis therapy initiation periods. Annual rates of serious fall injuries were 64.4 (95% CI, 62.7-66.2) and 107.8 (95% CI, 105.4-110.3) per 1,000 patient-years, respectively, in the pre- and post-dialysis therapy initiation periods (incidence rate ratio, 1.62; 95% CI, 1.56-1.67). Relative rates of serious fall injuries in the post- vs pre-dialysis initiation periods were of greater magnitude among patients who were younger (<75 years), had pre-end-stage renal disease nephrology care, had albumin levels > 3g/dL, were able to walk and transfer, did not need assistance with activities of daily living, and were not institutionalized compared with relative rates among their counterparts. Potential misclassification due to the use of claims data and survival bias among those initiating hemodialysis therapy. Among older Medicare beneficiaries receiving hemodialysis, serious fall injuries are common, the post-dialysis initiation period is a high-risk time for falls, and dialysis therapy initiation may be an important time to screen for fall risk factors and implement multifactorial fall prevention strategies. Copyright © 2017 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Paediatric Crohn Disease: Disease Activity and Growth in the BELCRO Cohort After 3 Years Follow-up.

PubMed

De Greef, Elisabeth; Hoffman, Ilse; Smets, Francoise; Van Biervliet, Stephanie; Bontems, Patrick; Hauser, Bruno; Paquot, Isabelle; Alliet, Philippe; Arts, Wim; Dewit, Olivier; De Vos, Martine; Baert, Filip; Bossuyt, Peter; Rahier, Jean-Francois; Franchimont, Denis; Vermeire, Severine; Fontaine, Fernand; Louis, Edouard; Coche, J C; Veereman, Gigi

2016-08-01

The Belgian registry for paediatric Crohn disease (BELCRO) cohort is a prospective, multicentre registry for newly diagnosed paediatric patients with Crohn disease (CD) (<18 years) recruited from 2008 to 2010 to identify predictive factors for disease activity and growth. Data from the BELCRO database were evaluated at diagnosis, 24 and 36 months follow-up. At month 36 (M36), data were available on 84 of the 98 patients included at diagnosis. Disease activity evolved as follows: inactive 5% to 70%, mild 19% to 24%, and moderate to severe 76% to 6%. None of the variables such as age, sex, diagnostic delay, type of treatment, disease location, disease activity at diagnosis, and growth were associated with disease activity at M36. Paediatricians studied significantly less patients with active disease at M36 compared with adult physicians. Sixty percent of the patients had biologicals as part of their treatment at M36. Adult gastroenterologists initiated biologicals significantly earlier. They were the only factor determining biologicals' initiation, not disease location or disease severity at diagnosis. Median body mass index (BMI) z score evolved from -0.97 (range -5.5-2.1) to 0.11 (range -3.4-2) and median height z score from -0.15 (range -3.4-1.6) to 0.12 (range -2.3-2.3) at M36. None of the variables mentioned above influenced growth over time. Present treatment strategies lead to good disease control in the BELCRO cohort after 3 years. Logistic regression analysis did not show any influence of disease location or present treatment strategy on disease activity and growth, but patients under paediatric care had significantly less severe disease at M36.

Canadian media representations of mad cow disease.

PubMed

Boyd, Amanda D; Jardine, Cynthia G; Driedger, S Michelle

2009-01-01

A Canadian case of bovine spongiform encephalopathy (BSE) or "mad cow disease" was confirmed in May, 2003. An in-depth content analysis of newspaper articles was conducted to understand the portrayal of BSE and variant Creutzfeldt-Jakob disease (vCJD) in the Canadian media. Articles in the "first 10 days" following the initial discovery of a cow with BSE in Canada on May 20, 2003, were examined based on the premise that these initial stories provide the major frames that dominate news media reporting of the same issue over time and multiple occurrences. Subsequent confirmed Canadian cases were similarly analyzed to determine if coverage changed in these later media articles. The results include a prominence of economic articles, de-emphasis of health aspects, and anchoring the Canadian outbreak to that of Britain's crisis. The variation in media representations between those in Canada and those documented in Britain are explored in this study.

A study on knowledge, attitudes and health behaviours regarding Alzheimer's disease among community residents in Tianjin, China.

PubMed

Yang, H-F; Cong, J-Y; Zang, X-Y; Jiang, N; Zhao, Y

2015-11-01

What is known on the subject? Several studies have measured the general public's knowledge and attitudes towards Alzheimer's disease; however, much of this work is based on western samples. Due to cultural differences, the western findings may be difficult to generalize to the Chinese general public. In addition, the few studies conducted in China were often restricted to a relatively narrow range of knowledge and attitudes. What this paper adds to existing knowledge? The general public had little knowledge of Alzheimer's disease, especially on the causes, symptoms and risk factors. In terms of attitudes, although the general public held positive attitudes towards persons with Alzheimer's disease, most of them were not sure whether or not to share a diagnosis of Alzheimer's disease with the patient. In daily life, only a low proportion of people kept mentally active. What are the implications for practice? A popularization of a wide range of knowledge about Alzheimer's disease needs to be undertaken, especially focusing on persons with low educational level and emphasizing the causes, symptoms and risk factors. Besides, there is a significant need to draw up evidence-based dietary and lifestyle guidelines for Alzheimer's disease risk reduction. Moreover, health promotion agencies should identify priority groups for Alzheimer's disease risk reduction initiatives, especially those with lower income, a lower level of knowledge on Alzheimer's disease and with chronic diseases. The purpose of this descriptive correlational cross-sectional study was to assess the current level of knowledge, attitudes and health behaviours regarding Alzheimer's disease among community residents in Tianjin, China and to identify factors related to these attributes. A convenience sample of 140 community-dwelling adults aged 20-75 years was selected to complete a researcher-designed questionnaire about Alzheimer's disease-related knowledge, attitudes and health behaviours. The findings revealed that 15.7% of the participants knew the risk factors for Alzheimer's disease. With regard to attitude, 138 participants (98.6%) believed that people with Alzheimer's disease should not be discriminated against, and 55.7% were not sure whether to share a diagnosis of Alzheimer's disease with the patient. In daily life, 28.6% of the participants pursued their interests and hobbies. A lower level of health behaviours was associated with lower income, presence of chronic diseases and a lower level of knowledge about Alzheimer's disease. These findings provide a strong case for population-level risk reduction initiatives to be undertaken, especially among people with lower income, a lower level of knowledge on Alzheimer's disease and with chronic diseases. © 2015 John Wiley & Sons Ltd.

Epigenetic Mechanisms of Transmission of Metabolic Disease across Generations.

PubMed

Sales, Vicencia Micheline; Ferguson-Smith, Anne C; Patti, Mary-Elizabeth

2017-03-07

Both human and animal studies indicate that environmental exposures experienced during early life can robustly influence risk for adult disease. Moreover, environmental exposures experienced by parents during either intrauterine or postnatal life can also influence the health of their offspring, thus initiating a cycle of disease risk across generations. In this Perspective, we focus on epigenetic mechanisms in germ cells, including DNA methylation, histone modification, and non-coding RNAs, which collectively may provide a non-genetic molecular legacy of prior environmental exposures and influence transcriptional regulation, developmental trajectories, and adult disease risk in offspring. Copyright © 2017 Elsevier Inc. All rights reserved.

Collaborative Initiative in Biomedical Imaging to Study Complex Diseases

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

Lin, Weili; Fiddy, Michael A.

2012-03-31

The work reported addressed these topics: Fluorescence imaging; Optical coherence tomography; X-ray interferometer/phase imaging system; Quantitative imaging from scattered fields, Terahertz imaging and spectroscopy; and Multiphoton and Raman microscopy.

Type 2 diabetes and incidence of cardiovascular diseases: a cohort study in 1·9 million people.

PubMed

Shah, Anoop Dinesh; Langenberg, Claudia; Rapsomaniki, Eleni; Denaxas, Spiros; Pujades-Rodriguez, Mar; Gale, Chris P; Deanfield, John; Smeeth, Liam; Timmis, Adam; Hemingway, Harry

2015-02-01

The contemporary associations of type 2 diabetes with a wide range of incident cardiovascular diseases have not been compared. We aimed to study associations between type 2 diabetes and 12 initial manifestations of cardiovascular disease. We used linked primary care, hospital admission, disease registry, and death certificate records from the CALIBER programme, which links data for people in England recorded in four electronic health data sources. We included people who were (or turned) 30 years or older between Jan 1, 1998, to March 25, 2010, who were free from cardiovascular disease at baseline. The primary endpoint was the first record of one of 12 cardiovascular presentations in any of the data sources. We compared cumulative incidence curves for the initial presentation of cardiovascular disease and used Cox models to estimate cause-specific hazard ratios (HRs). This study is registered at ClinicalTrials.gov (NCT01804439). Our cohort consisted of 1 921 260 individuals, of whom 1 887 062 (98·2%) did not have diabetes and 34 198 (1·8%) had type 2 diabetes. We observed 113 638 first presentations of cardiovascular disease during a median follow-up of 5·5 years (IQR 2·1-10·1). Of people with type 2 diabetes, 6137 (17·9%) had a first cardiovascular presentation, the most common of which were peripheral arterial disease (reported in 992 [16·2%] of 6137 patients) and heart failure (866 [14·1%] of 6137 patients). Type 2 diabetes was positively associated with peripheral arterial disease (adjusted HR 2·98 [95% CI 2·76-3·22]), ischaemic stroke (1·72 [1·52-1·95]), stable angina (1·62 [1·49-1·77]), heart failure (1·56 [1·45-1·69]), and non-fatal myocardial infarction (1·54 [1·42-1·67]), but was inversely associated with abdominal aortic aneurysm (0·46 [0·35-0·59]) and subarachnoid haemorrhage (0·48 [0·26-0.89]), and not associated with arrhythmia or sudden cardiac death (0·95 [0·76-1·19]). Heart failure and peripheral arterial disease are the most common initial manifestations of cardiovascular disease in type 2 diabetes. The differences between relative risks of different cardiovascular diseases in patients with type 2 diabetes have implications for clinical risk assessment and trial design. Wellcome Trust, National Institute for Health Research, and Medical Research Council. Copyright © 2015 Shah et al. Open Access article distributed under the terms of CC BY. Published by .. All rights reserved.

Determinants of Onset of Huntington's Disease with Behavioral Symptoms: Insight from 92 Patients.

PubMed

Lenka, Abhishek; Kamble, Nitish L; Sowmya, V; Jhunjhunwala, Ketan; Yadav, Ravi; Netravathi, M; Kandasamy, Mahesh; Moily, Nagaraj S; Purushottam, Meera; Jain, Sanjeev; Pal, Pramod Kumar

2015-01-01

Huntington's disease (HD) is a genetically mediated neurodegenerative disorder characterized by presence of involuntary movements, behavioral problems and cognitive dysfunctions. Though few patients with HD may have behavioral symptoms at onset of the disease, studies comparing patients with behavioral symptoms at the onset of HD with those having motor symptoms are sparse. Objective of this study is to determine the differences in the demographic and genetic characteristics of patients with behavioral symptom at the onset of HD from those with motor symptoms. A chart review of 92 patients with HD who had attended the neurology outpatient clinics of National Institute of Mental Health and Neurosciences, India was done. Demographic and genetic characteristics of HD patients with onset of the disease with initial behavioral symptoms (HD-iB) were compared with patients with onset of the disease with initial motor symptoms (HD-iM). The principal findings in our study were (i) higher proportion of patients with HD-iB had a positive family history of HD, (ii) maternal inheritance of HD was more frequent among those with HD-iB, and (iii) There is no significant difference between the CAG repeat length between HD-iB and HD-iM groups. Presence of family history of HD especially inheritance of HD from mother may be associated with behavioral symptoms at the onset of HD. CAG repeat length in patients with HD-iB does not differ from those with HD-iM.

Children's health and the environment: an overview.

PubMed

Landrigan, Philip J; Miodovnik, Amir

2011-01-01

Environmental pediatrics, the branch of pediatric medicine that studies the influence of the environment on children's health, has in the past decade grown exponentially. Rising rates of pediatric chronic disease and growing recognition of children's extensive exposures and great vulnerabilities to toxic hazards in the environment have catalyzed this expansion. New scientific initiatives have resulted. They include 14 Centers for Children's Environmental Health and Disease Prevention Research supported by the US National Institutes of Health and the US Environmental Protection Agency; a global network of Pediatric Environmental Health Specialty Units supported by the US Centers for Disease Control and Prevention/Agency for Toxic Substances and Disease Registry; new postdoctoral training programs in pediatric environmental medicine; and the National Children's Study, the largest prospective epidemiological study of children's health ever undertaken in the United States, which launched in 2009 and will follow 100,000 children from conception to age 21 to assess environmental influences on health and development. These research initiatives have delineated the exquisite vulnerability of fetuses, infants, and children to toxic hazards in the environment. They have led to discovery of new environmental causes of disease and disability in children. This issue of The Mount Sinai Journal of Medicine focuses on children's health and the environment. We have brought together thought leaders in children's environmental health to critically examine new research findings, to explore new opportunities for translating research to treatment and prevention, and to offer a vision for the future of this rapidly expanding field. © 2011 Mount Sinai School of Medicine.

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.

Improving Brain Magnetic Resonance Image (MRI) Segmentation via a Novel Algorithm based on Genetic and Regional Growth

PubMed Central

A., Javadpour; A., Mohammadi

2016-01-01

Background Regarding the importance of right diagnosis in medical applications, various methods have been exploited for processing medical images solar. The method of segmentation is used to analyze anal to miscall structures in medical imaging. Objective This study describes a new method for brain Magnetic Resonance Image (MRI) segmentation via a novel algorithm based on genetic and regional growth. Methods Among medical imaging methods, brains MRI segmentation is important due to high contrast of non-intrusive soft tissue and high spatial resolution. Size variations of brain tissues are often accompanied by various diseases such as Alzheimer’s disease. As our knowledge about the relation between various brain diseases and deviation of brain anatomy increases, MRI segmentation is exploited as the first step in early diagnosis. In this paper, regional growth method and auto-mate selection of initial points by genetic algorithm is used to introduce a new method for MRI segmentation. Primary pixels and similarity criterion are automatically by genetic algorithms to maximize the accuracy and validity in image segmentation. Results By using genetic algorithms and defining the fixed function of image segmentation, the initial points for the algorithm were found. The proposed algorithms are applied to the images and results are manually selected by regional growth in which the initial points were compared. The results showed that the proposed algorithm could reduce segmentation error effectively. Conclusion The study concluded that the proposed algorithm could reduce segmentation error effectively and help us to diagnose brain diseases. PMID:27672629

Allele-Specific Methylation Occurs at Genetic Variants Associated with Complex Disease

PubMed Central

Hutchinson, John N.; Raj, Towfique; Fagerness, Jes; Stahl, Eli; Viloria, Fernando T.; Gimelbrant, Alexander; Seddon, Johanna; Daly, Mark; Chess, Andrew; Plenge, Robert

2014-01-01

We hypothesize that the phenomenon of allele-specific methylation (ASM) may underlie the phenotypic effects of multiple variants identified by Genome-Wide Association studies (GWAS). We evaluate ASM in a human population and document its genome-wide patterns in an initial screen at up to 380,678 sites within the genome, or up to 5% of the total genomic CpGs. We show that while substantial inter-individual variation exists, 5% of assessed sites show evidence of ASM in at least six samples; the majority of these events (81%) are under genetic influence. Many of these cis-regulated ASM variants are also eQTLs in peripheral blood mononuclear cells and monocytes and/or in high linkage-disequilibrium with variants linked to complex disease. Finally, focusing on autoimmune phenotypes, we extend this initial screen to confirm the association of cis-regulated ASM with multiple complex disease-associated variants in an independent population using next-generation bisulfite sequencing. These four variants are implicated in complex phenotypes such as ulcerative colitis and AIDS progression disease (rs10491434), Celiac disease (rs2762051), Crohn's disease, IgA nephropathy and early-onset inflammatory bowel disease (rs713875) and height (rs6569648). Our results suggest cis-regulated ASM may provide a mechanistic link between the non-coding genetic changes and phenotypic variation observed in these diseases and further suggests a route to integrating DNA methylation status with GWAS results. PMID:24911414

Experimental Transmission of Chronic Wasting Disease (CWD) from Elk (Cervus elaphus nelsoni) and White-tailed Deer (Odocoileus virginianus) to Fallow Deer (Dama dama) by Intracerebral Route: Final Report

USDA-ARS?s Scientific Manuscript database

In this communication we report final observations on experimental transmission of chronic wasting disease (CWD) from elk (Cervus elaphus nelsoni) and white tailed deer (Odocoileus virginianus) to fallow deer (Dama dama). The study was terminated 5 years after it was initiated. Thirteen fawns were i...

Implications of DRG Classification in a Bundled Payment Initiative for COPD.

PubMed

Parekh, Trisha M; Bhatt, Surya P; Westfall, Andrew O; Wells, James M; Kirkpatrick, Denay; Iyer, Anand S; Mugavero, Michael; Willig, James H; Dransfield, Mark T

2017-12-01

Institutions participating in the Medicare Bundled Payments for Care Improvement (BPCI) initiative invest significantly in efforts to reduce readmissions and costs for patients who are included in the program. Eligibility for the BPCI initiative is determined by diagnosis-related group (DRG) classification. The implications of this methodology for chronic diseases are not known. We hypothesized that patients included in a BPCI initiative for chronic obstructive pulmonary disease (COPD) would have less severe illness and decreased hospital utilization compared with those excluded from the bundled payment initiative. Retrospective observational study. We sought to determine the clinical characteristics and outcomes of Medicare patients admitted to the University of Alabama at Birmingham Hospital with acute exacerbations of COPD between 2012 and 2014 who were included and excluded in a BPCI initiative. Patients were included in the analysis if they were discharged with a COPD DRG or with a non-COPD DRG but with an International Classification of Diseases, Ninth Revision code for COPD exacerbation. Six hundred and ninety-eight unique patients were discharged for an acute exacerbation of COPD; 239 (34.2%) were not classified into a COPD DRG and thus were excluded from the BPCI initiative. These patients were more likely to have intensive care unit (ICU) admissions (63.2% vs 4.4%, respectively; P <.001) and require noninvasive (46.9% vs 6.5%; P <.001) and invasive mechanical ventilation (41.4% vs 0.7%; P <.001) during their hospitalization than those in the initiative. They also had a longer ICU length of stay (5.2 vs 1.8 days; P = .011), longer hospital length of stay (10.3 days vs 3.9 days; P <.001), higher in-hospital mortality (14.6% vs 0.7%; P <.001), and greater hospitalization costs (median = $13,677 [interquartile range = $7489-$23,054] vs $4281 [$2718-$6537]; P <.001). The use of DRGs to identify patients with COPD for inclusion in the BPCI initiative led to the exclusion of more than one-third of patients with acute exacerbations who had more severe illness and worse outcomes and who may benefit most from the additional interventions provided by the initiative.

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.

76 FR 19474 - Notice of Intent to Seek Approval To Extend a Current Information Collection

Federal Register 2010, 2011, 2012, 2013, 2014

2011-04-07

... disease-related goals. Examples of areas of research that will not be considered are epidemiology... Collection: Application for NATO Advanced Study Institutes Travel Award and NATO Advanced Study Institutes.... Abstract: The North Atlantic Treaty Organization (NATO) initiated its Advanced Study Institutes Program in...

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 lower likelihood of DMARD initiation. Among managed care enrollees in the present analysis, 37% of patients newly diagnosed with RA were not being treated with DMARDs in the first 12 months after diagnosis. Time to DMARD initiation plateaued after 90 days, suggesting that if a patient was not prescribed a DMARD soon after RA diagnosis, he or she was not likely to receive one. Copyright © 2012 Elsevier HS Journals, Inc. All rights reserved.

Implementation of a drug-use and disease-state management program.

PubMed

Skledar, S J; Hess, M M

2000-12-15

A drug-use and disease-state management (DUDSM) program was instituted in 1996 at a teaching hospital associated with a large nonprofit health care system. The program's goals are to optimize pharmacotherapeutic regimens, evaluate health outcomes of identified disease states, and evaluate the economic impact of pharmacotherapeutic options for given disease states by developing practice guidelines. Through a re-engineering process, resources within the pharmacy department were identified that could be devoted to the DUDSM program, including the use of clinical pharmacy specialists, promotion of staff pharmacists into the DUDSM program, a pharmacy technician, and information systems support. A strength of the program is its systematic approach for developing and implementing new initiatives, as well as monitoring compliance with all initiatives on an ongoing basis. The initiative-design process incorporates continuous quality improvement principles, outcome design and evaluation, competency assessment for all pharmacists, multidisciplinary collaboration, and sophisticated information systems. Seventy-five initiatives have been implemented, ranging from simple dose-optimization strategies for specific drugs to complicated practice guidelines for managing specific disease states. Improved patient outcomes have been documented, including reduced length of stay, postsurgical wound infection, adverse drug reactions, and medication errors. Documented cost savings exceeded $4 million annually for fiscal years 1996-97 through 1999-2000. Overall compliance with DUDSM initiatives exceeds 80%, and physician service profiling has been initiated to monitor variant prescribing. The DUDSM program has successfully integrated practice guidelines into therapeutic decision-making, resulting in improved patient-care outcomes and cost savings.

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

PubMed

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

2011-04-01

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

[Autosomal dominant polycystic kidney disease in hemodialysis patients in Southern Brazil].

PubMed

Alves, Everton Fernando; Tsuneto, Luiza Tamie; Pelloso, Sandra Marisa; Torres, Paulo Roberto Aranha; Otto, Guido Luis Gomes; Silva, Adaelson Alves; Obregon, José Miguel Viscarra; Silva, Letícia Nicoletti; Carvalho, Maria Dalva de Barros

2014-01-01

Autosomal dominant polycystic kidney disease is the most common hereditary renal disease in humans. To examine the prevalence, clinical and laboratory characteristics of patients with polycystic kidneys and relate disease manifestations by gender. This was an observational and retrospective study. All the medical records of patients with polycystic kidneys who initiated hemodialysis between 1995 and 2012, in four centers that treat patients of the coverage area of the 15th regional health Paraná (Brazil), were analyzed. The study included 48 patients with polycystic kidneys, the primary cause of stage 5 CKD. Disease prevalence was one in 10,912 people. The average age of dialysis initiation was 50.7 years and the follow-up time on dialysis until transplantation (36.5 months) was lower among men. Hypertension was the most frequent diagnosis in 73% of patients, predominantly in women (51.4%). The liver cyst was the most frequent extrarenal manifestations in men (60.0%). The death occurred in 10.4% of patients using hemodialysis, and 60% of men. The class of antihypertensive drug used was that acts on the renin-angiotensin system with higher frequency of use among women (53.3%). The post-dialysis urea was significantly higher in men. The prevalence of the disease is low among hemodialysis patients in southern Brazil. The differences observed between genders, with the exception of the post-dialysis urea, were not significant. The findings are different from those reported in North America and Europe.

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.

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 group (11.3 [5.8]) than in the initial levodopa group (8.6 [4.7]) (P < .001). Mean (SD) changes from baseline in the total Unified Parkinson's Disease Rating Scale score did not significantly differ between the initial pramipexole (2.4 [17.4]) and initial levodopa (0.5 [17.1]) groups (P = .11). The policies of initial pramipexole and initial levodopa use followed by open-label levodopa use resulted in similar self-reported disability 6 years after randomization. Persistent differences favoring initial pramipexole were seen in the rates of dopaminergic motor complications, with less severe somnolence favoring initial levodopa. Trial Registration clinicaltrials.gov Identifier: NCT00804479.

Vegetarian diets in the Adventist Health Study 2: a review of initial published findings1234

PubMed Central

Orlich, Michael J; Fraser, Gary E

2014-01-01

The Adventist Health Study 2 is a large cohort that is well suited to the study of the relation of vegetarian dietary patterns to health and disease risk. Here we review initial published findings with regard to vegetarian diets and several health outcomes. Vegetarian dietary patterns were associated with lower body mass index, lower prevalence and incidence of diabetes mellitus, lower prevalence of the metabolic syndrome and its component factors, lower prevalence of hypertension, lower all-cause mortality, and in some instances, lower risk of cancer. Findings with regard to factors related to vegetarian diets and bone health are also reviewed. These initial results show important links between vegetarian dietary patterns and improved health. PMID:24898223

Melanoma: a global perspective.

PubMed

Ossio, Raul; Roldán-Marín, Rodrigo; Martínez-Said, Héctor; Adams, David J; Robles-Espinoza, Carla Daniela

2017-07-01

Most of our current knowledge of melanoma is derived from the study of patients from populations of European descent, for whom public health, sun protection initiatives and screening measures have appreciably decreased disease mortality. Notably, some melanoma subtypes that most commonly develop in other populations are not associated with exposure to ultraviolet (UV) light, suggesting a different disease aetiology. Further study of these subtypes is necessary to understand their risk factors and genomic architecture, and to tailor therapies and public health campaigns to benefit patients of all ethnic groups.

Clinical features of adult-onset chronic active Epstein-Barr virus infection: a retrospective analysis.

PubMed

Arai, Ayako; Imadome, Ken-Ichi; Watanabe, Yuko; Yoshimori, Mayumi; Koyama, Takatoshi; Kawaguchi, Takeharu; Nakaseko, Chiaki; Fujiwara, Shigeyoshi; Miura, Osamu

2011-05-01

We performed a retrospective analysis of patients with adult-onset chronic active Epstein-Barr virus infection (CAEBV). First, we analyzed five patients (aged 28-72) diagnosed at our hospitals with EBV-infected clonally proliferating T cells. Four patients were administered cyclophosphamide/doxorubicin/vincristine/prednisone (CHOP) chemotherapy, but no remarkable decrease of viral load was observed in three of the patients. The other patient died 19 days after initiation of CHOP treatment due to disease progression. Addition of high-dose cytarabine to the regimens of two of the patients was discontinued shortly after administration, due to the development of grade 4 pericardial effusion. Together, these regimens may be insufficient for treating adult-onset CAEBV. We next reviewed 23 adult-onset CAEBV patients, adding 18 previously reported patients to the five patients described in the present study. T cells were frequently infected (87%), whereas NK- and T-cell types are known to be almost equally prevalent in childhood-onset cases. The time duration from the onset of disease to initiation of treatment averaged 20 months. Reports showed that 12 patients died; seven patients died at an average of 8 months after initiation of treatment. Patients' disease courses seemed to be rapidly progressive and more aggressive than those of childhood-onset cases. More cases must be studied to clarify clinical features and establish an optimal treatment strategy.

Arteriovenous fistula maturation in patients with permanent access created prior to or after hemodialysis initiation.

PubMed

Duque, Juan C; Martinez, Laisel; Tabbara, Marwan; Dvorquez, Denise; Mehandru, Sushil K; Asif, Arif; Vazquez-Padron, Roberto I; Salman, Loay H

2017-05-15

Multiple factors and comorbidities have been implicated in the ability of arteriovenous fistulas (AVF) to mature, including vessel anatomy, advanced age, and the presence of coronary artery disease or peripheral vascular disease. However, little is known about the role of uremia on AVF primary failure. In this study, we attempt to evaluate the effect of uremia on AVF maturation by comparing AVF outcomes between pre-dialysis chronic kidney disease (CKD) stage five patients and those who had their AVF created after hemodialysis (HD) initiation. We included 612 patients who underwent AVF creation between 2003 and 2015 at the University of Miami Hospital and Jackson Memorial Hospital. Effects of uremia on primary failure were evaluated using univariate statistical comparisons and multivariate logistic regression analyses. Primary failure occurred in 28.1% and 26.3% of patients with an AVF created prior to or after HD initiation, respectively (p = 0.73). The time of HD initiation was not associated with AVF maturation in multivariate logistic regression analysis (p = 0.57). In addition, pre-operative blood urea nitrogen (p = 0.78), estimated glomerular filtration rate (p = 0.66), and serum creatinine levels (p = 0.14) were not associated with AVF primary failure in pre-dialysis patients. Our results show that clearance of uremia with regular HD treatments prior to AVF creation does not improve the frequency of vascular access maturation.

Septic acute kidney injury patients in emergency department: The risk factors and its correlation to serum lactate.

PubMed

Hsu, Yin-Chou; Hsu, Chih-Wei

2018-05-15

Acute kidney injury (AKI) is a common complication in septic patients, imposing a heavy burden of illness in terms of morbidity and mortality. Serum lactate is a widely used marker predicting the severity of sepsis. A paucity of research has investigated septic AKI in emergency departments (EDs) and its correlation with initial serum lactate level. This study aimed at identifying risk factors for septic AKI and clarifying the link between initial serum lactate level and septic AKI in ED patients. A retrospective cohort study was conducted at a single tertiary referral medical center. The medical records of all adult ED patients with measurement of serum lactate and creatinine between January 2012 and December 2016 were reviewed. A total of 696 septic patients were stratified into AKI and non-AKI groups according to Acute Kidney Injury Network (AKIN) criteria for further statistical analysis. Ninety-nine septic patients (14.2%) had AKI, with AKIN-I, AKIN-II, and AKIN-III in 71.7%, 11.1%, and 17.2% of patients, respectively. Compared with the non-AKI group, the AKI group had a significantly higher mortality rate (71.7% vs. 21.3%, p < 0.001). Independent risk factors for septic AKI included liver disease (adjusted odds ratio [AOR] = 2.02, 95% confidence interval [CI] = 1.16-3.52), diabetes mellitus (AOR = 1.73, 95% CI = 1.11-2.69), chronic kidney disease (AOR = 1.68, 95% CI = 1.06-2.66), and initial serum lactate (AOR = 1.08, 95% CI = 1.02-1.14). Patients with septic AKI had an overwhelmingly higher mortality rate. The comorbidities of liver disease, diabetes mellitus, and chronic kidney disease were correlated with septic AKI and in combination with an elevated initial serum lactate level had predictive regarding AKI and further mortality in ED septic patients. Copyright © 2018 Elsevier Inc. All rights reserved.

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.

Chronic disease prevalence and associations in a cohort of Australian men: The Florey Adelaide Male Ageing Study (FAMAS)

PubMed Central

Martin, Sean A; Haren, Matthew T; Taylor, Anne W; Middleton, Sue M; Wittert, Gary A

2008-01-01

Background An increasing proportion of Australia's chronic disease burden is carried by the ageing male. The aim of this study was to determine the prevalence of asthma, cancer, diabetes, angina and musculoskeletal conditions and their relationship to behavioural and socio-demographic factors in a cohort of Australian men. Methods Self-reports of disease status were obtained from baseline clinic visits (August 2002 – July 2003 & July 2004 – May 2005) from 1195 randomly selected men, aged 35–80 years and living in the north-west regions of Adelaide. Initially, relative risks were assessed by regression against selected variables for each outcome. Where age-independent associations were observed with the relevant chronic disease, independent variables were fitted to customized multiadjusted models. Results The prevalence of all conditions was moderately higher in comparison to national data for age-matched men. In particular, there was an unusually high rate of men with cancer. Multiadjusted analyses revealed age as a predictor of chronic conditions (type 2 diabetes mellitus, angina, cancer & osteoarthritis). A number of socio-demographic factors, independent of age, were associated with chronic disease, including: low income status (diabetes), separation/divorce (asthma), unemployment (cancer), high waist circumference (diabetes), elevated cholesterol (angina) and a family history of obesity (angina). Conclusion Socio-demographic factors interact to determine disease status in this broadly representative group of Australian men. In addition to obesity and a positive personal and family history of disease, men who are socially disadvantaged (low income, unemployed, separated) should be specifically targeted by public health initiatives. PMID:18664294

The Roles of Mitochondrial Damage-Associated Molecular Patterns in Diseases

PubMed Central

Nakahira, Kiichi; Hisata, Shu

2015-01-01

Abstract Significance: Mitochondria, vital cellular power plants to generate energy, are involved in immune responses. Mitochondrial damage-associated molecular patterns (DAMPs) are molecules that are released from mitochondria to extracellular space during cell death and include not only proteins but also DNA or lipids. Mitochondrial DAMPs induce inflammatory responses and are critically involved in the pathogenesis of various diseases. Recent Advances: Recent studies elucidate the molecular mechanisms by which mitochondrial DAMPs are released and initiate immune responses by use of genetically modulated cells or animals. Importantly, the levels of mitochondrial DAMPs in patients are often associated with severity and prognosis of human diseases, such as infection, asthma, ischemic heart disease, and cancer. Critical Issues: Although mitochondrial DAMPs can represent proinflammatory molecules in various experimental models, their roles in human diseases may be multifunctional and complex. It remains unclear where and how mitochondrial DAMPs are liberated into extracellular spaces and exert their biological functions particularly in vivo. In addition, while mitochondria can secrete several types of DAMPs during cell death, the interaction of each mitochondrial DAMP (e.g., synergistic effects) remains unclear. Future Directions: Regulation of mitochondrial DAMP-mediated immune responses may be important to alter the progression of human diseases. In addition, measuring mitochondrial DAMPs in patients may be clinically useful as biomarkers to predict prognosis or response to therapies. Further studies of the mechanisms by which mitochondrial DAMPs impact the initiation and progression of diseases may lead to the development of therapeutics specifically targeting this pathway. Antioxid. Redox Signal. 23, 1329–1350. PMID:26067258

Public health adaptation to climate change in Canadian jurisdictions.

PubMed

Austin, Stephanie E; Ford, James D; Berrang-Ford, Lea; Araos, Malcolm; Parker, Stephen; Fleury, Manon D

2015-01-12

Climate change poses numerous risks to the health of Canadians. Extreme weather events, poor air quality, and food insecurity in northern regions are likely to increase along with the increasing incidence and range of infectious diseases. In this study we identify and characterize Canadian federal, provincial, territorial and municipal adaptation to these health risks based on publically available information. Federal health adaptation initiatives emphasize capacity building and gathering information to address general health, infectious disease and heat-related risks. Provincial and territorial adaptation is varied. Quebec is a leader in climate change adaptation, having a notably higher number of adaptation initiatives reported, addressing almost all risks posed by climate change in the province, and having implemented various adaptation types. Meanwhile, all other Canadian provinces and territories are in the early stages of health adaptation. Based on publically available information, reported adaptation also varies greatly by municipality. The six sampled Canadian regional health authorities (or equivalent) are not reporting any adaptation initiatives. We also find little relationship between the number of initiatives reported in the six sampled municipalities and their provinces, suggesting that municipalities are adapting (or not adapting) autonomously.

Prolonged Culture of Aligned Skeletal Myotubes on Micromolded Gelatin Hydrogels

PubMed Central

Bettadapur, Archana; Suh, Gio C.; Geisse, Nicholas A.; Wang, Evelyn R.; Hua, Clara; Huber, Holly A.; Viscio, Alyssa A.; Kim, Joon Young; Strickland, Julie B.; McCain, Megan L.

2016-01-01

In vitro models of skeletal muscle are critically needed to elucidate disease mechanisms, identify therapeutic targets, and test drugs pre-clinically. However, culturing skeletal muscle has been challenging due to myotube delamination from synthetic culture substrates approximately one week after initiating differentiation from myoblasts. In this study, we successfully maintained aligned skeletal myotubes differentiated from C2C12 mouse skeletal myoblasts for three weeks by utilizing micromolded (μmolded) gelatin hydrogels as culture substrates, which we thoroughly characterized using atomic force microscopy (AFM). Compared to polydimethylsiloxane (PDMS) microcontact printed (μprinted) with fibronectin (FN), cell adhesion on gelatin hydrogel constructs was significantly higher one week and three weeks after initiating differentiation. Delamination from FN-μprinted PDMS precluded robust detection of myotubes. Compared to a softer blend of PDMS μprinted with FN, myogenic index, myotube width, and myotube length on μmolded gelatin hydrogels was similar one week after initiating differentiation. However, three weeks after initiating differentiation, these parameters were significantly higher on μmolded gelatin hydrogels compared to FN-μprinted soft PDMS constructs. Similar results were observed on isotropic versions of each substrate, suggesting that these findings are independent of substrate patterning. Our platform enables novel studies into skeletal muscle development and disease and chronic drug testing in vitro. PMID:27350122

Exploratory Analysis of Time from HIV Diagnosis to ART Start, Factors and effect on survival: A longitudinal follow up study at seven teaching hospitals in Ethiopia.

PubMed

Teklu, Alula M; Delele, Kesetebirhan; Abraha, Mulu; Belayhun, Bekele; Gudina, Esayas Kebede; Nega, Abiy

2017-02-01

The HIV care in Ethiopia has reached 79% coverage. The timeliness of the care provided at the different levels in the course of the disease starting from knowing HIV positive status to ART initiation is not well known. This study intends to explore the timing of the care seeking, the care provision and associated factors. This is a longitudinal follow-up study at seven university hospitals. Patients enrolled in HIV care from September 2005 to December 2013 and aged ≥14 years were studied. Different times in the cascade of HIV care were examined including the duration from date HIV diagnosed to enrollment in HIV care, duration from enrollment to eligibility for ART and time from eligibility to initiation of ART. Ordinal logistic regression was used to investigate their determinants while the effect of these periods on survival of patients was determined using cox-proportional hazards regression. 4159 clients were studied. Time to enrollment after HIV test decreased from 39 days in 2005 to 1 day after 2008. It took longer if baseline CD4 was higher, and eligibility for ART was assessed late. Young adults, lower baseline CD4, HIV diagnosis<2008, late enrollment, and early eligibility assessment were associated with early ART initiation. Male gender, advanced disease stage and lower baseline CD4 were consistent risk factors for mortality. Time to enrollment and duration of ART eligibility assessment as well as ART initiation time after eligibility is improving. Further study is required to identify why mortality is slightly increasing after 2010.

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

[From the newborn infant to the child, to the adult: historia magistra vitae].

PubMed

Cataldi, L; Buonsenso, D

2008-08-01

The hypothesis of the prenatal programming of adult diseases took on increasing interest from the moment that, in the 60s, an epidemiological association was proposed between low birth weight and cardiovascular diseases. In the last 20 years it has been demonstrated that individuals with low weight, low stature and thinness at birth have a higher risk of developing cardiovascular diseases and type 2 diabetes. Animal and clinical studies are casting light on the biological mechanisms underlying the association between modified development in the uterus and diseases, and on how growth in adolescence and in adult life can modulate this initial proneness to disease. One of the mechanisms that has aroused most interest among researchers is the reduced number of nephrons, associated with low birth weight, which predisposes to glomerulosclerosis and increased systemic arterial pressure in adult life. A correlation has also been found between low weight at birth and peripheral resistance to insulin. Nevertheless, it is thought that modified prenatal development is only a predisposing factor, open to profound influences in the course of postnatal development. It has in fact been demonstrated that accelerated development in the period of infancy and adolescence can extend the initial condition of neonatal suffering. Indirectly these studies renew and at the same time extend the concept of prevention, a priority aim of the physician of the third millennium.

A potential therapeutic role for aldose reductase inhibitors in the treatment of endotoxin-related inflammatory diseases

PubMed Central

Pandey, Saumya; Srivastava, Satish K

2012-01-01

Introduction Aldose reductase (AR) initially thought to be involved in the secondary diabetic complications because of its glucose reducing potential. However, evidence from recent studies indicates that AR is an excellent reducer of a number of lipid peroxidation-derived aldehydes as well as their glutathione conjugates, which regulate inflammatory signals initiated by oxidants such as cytokines, growth factors and bacterial endotoxins, and revealed the potential use of AR inhibition as an approach to prevent inflammatory complications. Areas covered An extensive Internet and Medline search was performed to retrieve information on understanding the role of AR inhibition in the pathophysiology of endotoxin-mediated inflammatory disorders. Overall, inhibition of AR appears to be a promising strategy for the treatment of endotoxemia, sepsis and other related inflammatory diseases. Expert opinion Current knowledge provides enough evidence to indicate that AR inhibition is a logical therapeutic strategy for the treatment of endotoxin-related inflammatory diseases. Since, AR inhibitors have already gone to Phase-iii clinical studies for diabetic complications and found to be safe for human use, their use in endotoxin–related inflammatory diseases could be expedited. However, one of the major challenges will be the discovery of AR regulated clinically-relevant biomarkers to identify susceptible individuals at risk of developing inflammatory diseases, thereby warranting future research in this area. PMID:22283786

Psychological Predictors of Mortality: Evidence from a 41-Year Prospective Study.

ERIC Educational Resources Information Center

Graves, Pirkko L.; And Others

The Precursors Study, initiated in 1946, has focused on searching for links between psychological patterns and future disease and death. Gathering a broad spectrum of psychobiological characteristics from a large group of medical students, this study has continued year after year. This study examined the role of psychological factors on mortality,…

Lessons Learned from a Decade of Sudden Oak Death in California: Evaluating Local Management

NASA Astrophysics Data System (ADS)

Alexander, Janice; Lee, Christopher A.

2010-09-01

Sudden Oak Death has been impacting California’s coastal forests for more than a decade. In that time, and in the absence of a centrally organized and coordinated set of mandatory management actions for this disease in California’s wildlands and open spaces, many local communities have initiated their own management programs. We present five case studies to explore how local-level management has attempted to control this disease. From these case studies, we glean three lessons: connections count, scale matters, and building capacity is crucial. These lessons may help management, research, and education planning for future pest and disease outbreaks.

Lessons Learned from a Decade of Sudden Oak Death in California: Evaluating Local Management

PubMed Central

Alexander, Janice

2010-01-01

Sudden Oak Death has been impacting California’s coastal forests for more than a decade. In that time, and in the absence of a centrally organized and coordinated set of mandatory management actions for this disease in California’s wildlands and open spaces, many local communities have initiated their own management programs. We present five case studies to explore how local-level management has attempted to control this disease. From these case studies, we glean three lessons: connections count, scale matters, and building capacity is crucial. These lessons may help management, research, and education planning for future pest and disease outbreaks. PMID:20559634

The importance of studying sex differences in disease: The example of multiple sclerosis.

PubMed

Golden, Lisa C; Voskuhl, Rhonda

2017-01-02

To date, scientific research has often focused on one sex, with assumptions that study of the other sex would yield similar results. However, many diseases affect males and females differently. The sex of a patient can affect the risk for both disease susceptibility and progression. Such differences can be brought to the laboratory bench to be investigated, potentially bringing new treatments back to the clinic. This method of research, known as a "bedside to bench to bedside" approach, has been applied to studying sex differences in multiple sclerosis (MS). Females have greater susceptibly to MS, while males have worse disease progression. These two characteristics of the disease are influenced by the immune system and the nervous system, respectively. Thus, sex differences in each system must be studied. Personalized medicine has been at the forefront of research recently, and studying sex differences in disease fits with this initiative. This review will discuss the known sex differences in MS and highlight how investigating them can lead to new insights and potential treatments for both men and women. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Flight behavior and performance of Rhodnius pallescens (Hemiptera: Reduviidae) on a tethered flight mill.

PubMed

Castro, Lauren A; Peterson, Jennifer K; Saldana, Azael; Perea, Milixa Y; Calzada, Jose E; Pineda, Vanessa; Dobson, Andrew P; Gottdenker, Nicole L

2014-09-01

ABSTRACT Flight dispersal of the triatomine bug species Rhodnius pallescens Barber, the principal vector of Chagas disease in Panama, is an important mechanism for spreading Trypanosoma cruzi, causative agent of Chagas disease. This study measures R. pallescens flight performance using a tethered flight mill both when uninfected, and when infected with T. cruzi or Trypanosoma rangeli. Forty-four out of the 48 (91.7%) insects initiated flight across all treatments, and trypanosome infection did not significantly impact flight initiation. Insects from all treatments flew a cumulative distance ranging from 0.5 to 5 km before fatiguing. The median cumulative distance flown before insect fatigue was higher in T. cruzi- and T. rangeli-infected insects than in control insects; however, this difference was not statistically significant. There was a positive relationship between parasite load ingested and time until flight initiation in T. rangeli-infected bugs, and T. rangeli- and T. cruzi-infected females flew significantly faster than males at different time points. These novel findings allow for a better understanding of R. pallescens dispersal ability and peridomestic management strategies for the prevention of Chagas disease in Panama.

Initial condition of stochastic self-assembly

NASA Astrophysics Data System (ADS)

Davis, Jason K.; Sindi, Suzanne S.

2016-02-01

The formation of a stable protein aggregate is regarded as the rate limiting step in the establishment of prion diseases. In these systems, once aggregates reach a critical size the growth process accelerates and thus the waiting time until the appearance of the first critically sized aggregate is a key determinant of disease onset. In addition to prion diseases, aggregation and nucleation is a central step of many physical, chemical, and biological process. Previous studies have examined the first-arrival time at a critical nucleus size during homogeneous self-assembly under the assumption that at time t =0 the system was in the all-monomer state. However, in order to compare to in vivo biological experiments where protein constituents inherited by a newly born cell likely contain intermediate aggregates, other possibilities must be considered. We consider one such possibility by conditioning the unique ergodic size distribution on subcritical aggregate sizes; this least-informed distribution is then used as an initial condition. We make the claim that this initial condition carries fewer assumptions than an all-monomer one and verify that it can yield significantly different averaged waiting times relative to the all-monomer condition under various models of assembly.

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.

Prevalence of Periodontal Disease in the General Population of India-A Systematic Review.

PubMed

Shewale, Akhilesh H; Gattani, Deepti R; Bhatia, Nidhi; Mahajan, Rupali; Saravanan, S P

2016-06-01

Periodontal disease is a chronic inflammatory disease resulting in destruction of tissues and structures surrounding the teeth thus, if left untreated causes loss of teeth and ultimately results in edentulism, posing a great negative impact on individuals' quality of life. Hence the global epidemiological data suggests periodontal disease to be one of a major burden on oral diseases. To reduce this burden it is necessary to know the true prevalence of the disease according to which proper initiatives can be formulated. India being home to nearly 1.2 billion people and one amongst the rapidly developing country, its population requires being systemically as well as orally healthy to lead a good quality of life. However due to large heterogenecity amongst its residing population in terms of geographical area, culture, education, socioeconomic status, a variety of oral diseases like periodontal diseases are prevalent here. Even though the early studies suggested that the population is highly susceptible to the disease, the true prevalence of periodontal disease has not been found yet due to paucity in literature available. To systematically review the available literature taken from various parts of India and find the prevalence rate of periodontal disease amongst the general population of India. A literature search was performed using PUB MED, COCHRANE and EMBASE databases on August 6, 2015. Following full text assessment a thorough references search was made and potential studies were included. A Quality assessment of retrieved articles from 2(nd) round was done using a self designed questionnaire and only field survey studies were included in the systematic review. The literature search yielded six studies which had performed field surveys to find the prevalence of periodontal disease in their respective areas. These studies have observed different sets of age groups and the same has been accomplished by using Community Periodontal Index (CPI) or Community Periodontal Index of Treatment Needs (CPITN). It was also found that no prevalence studies have been carried out in few North and North Eastern states and Union Territories of India. Due to non-availability of same age groups in selected studies an overall prevalence rate could not be obtained. However, it was observed that few areas of states like West Bengal, Uttar Pradesh and Assam have reported a prevalence rate of periodontal disease of more than 85% in their general population. The data from the present systematic review calls for a combined initiative from the Government of India and Dental council of India to have a nationwide multicentric prevalence studies to obtain the true prevalence rate of periodontal disease in India and interventions should be provided for the same to maintain the oral health and quality of life of the affected population.

76 FR 82299 - Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Data...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-12-30

... Autism and Other Developmental Disabilities Research and Epidemiologic Studies, RFA DD12-001, Initial... evaluation of applications received in response to ``Data Coordinating Center for Autism and Other...

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.

Programmed initiation of hemodialysis for systemic amyloidosis patients associated with rheumatoid arthritis.

PubMed

Kuroda, Takeshi; Tanabe, Naohito; Kobayashi, Daisuke; Sato, Hiroe; Wada, Yoko; Murakami, Shuichi; Sakatsume, Minoru; Nakano, Masaaki; Narita, Ichiei

2011-09-01

Reactive amyloidosis is a serious systemic disease in rheumatoid arthritis (RA). Amyloid protein can be deposited in kidneys, heart or gastrointestinal tract leading to organ failure. Renal involvement is a well-known complication in amyloidosis as this may culminate in end-stage renal disease (ESRD). Hemodialysis (HD) is always considered the treatment of choice for such patients; however, the prognosis is usually poor due to a large number of sudden deaths immediately following HD therapy. To circumvent the problem of HD initiation while instituting HD safety, we devised a plan to start HD and compare patient's survival with our previous data. Sixty-three patients were treated with HD. They were categorized according to the initiation of first dialysis. All patients were divided into planned, unplanned and programmed initiation groups. First dialysis that had been initiated as not urgent was considered 'planned' (20 patients). First dialysis that had been performed urgently for life-threatening renal insufficiency was considered 'unplanned' (31 patients). First dialysis that had been initiated as not urgent and according to our dialysis program was considered 'programmed' (12 patients). Survival of these 63 patients from the initiation of HD at 38 days was 75%, at 321 days was 50% and at 1,784 days was 25%. Patients with unplanned initiation of HD showed a significant poor survival compared with those of both planned and programmed initiation. Additionally, patients with planned and programmed initiation of HD showed no significant difference for the patients' survival. Our study demonstrates that patients with amyloidosis have a higher mortality rate. Nevertheless, programmed initiation of HD will improve the prognosis of patients with ESRD. Such possibility needs to be considered in more detail in the future.

Rodent Models of Experimental Endometriosis: Identifying Mechanisms of Disease and Therapeutic Targets

PubMed Central

Bruner-Tran, Kaylon L.; Mokshagundam, Shilpa; Herington, Jennifer L.; Ding, Tianbing; Osteen, Kevin G.

2018-01-01

Background: Although it has been more than a century since endometriosis was initially described in the literature, understanding the etiology and natural history of the disease has been challenging. However, the broad utility of murine and rat models of experimental endometriosis has enabled the elucidation of a number of potentially targetable processes which may otherwise promote this disease. Objective: To review a variety of studies utilizing rodent models of endometriosis to illustrate their utility in examining mechanisms associated with development and progression of this disease. Results: Use of rodent models of endometriosis has provided a much broader understanding of the risk factors for the initial development of endometriosis, the cellular pathology of the disease and the identification of potential therapeutic targets. Conclusion: Although there are limitations with any animal model, the variety of experimental endometriosis models that have been developed has enabled investigation into numerous aspects of this disease. Thanks to these models, our under-standing of the early processes of disease development, the role of steroid responsiveness, inflammatory processes and the peritoneal environment has been advanced. More recent models have begun to shed light on how epigenetic alterations con-tribute to the molecular basis of this disease as well as the multiple comorbidities which plague many patients. Continued de-velopments of animal models which aid in unraveling the mechanisms of endometriosis development provide the best oppor-tunity to identify therapeutic strategies to prevent or regress this enigmatic disease.

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 (1.33, 1.09 to 1.63), intracerebral haemorrhage (1.37, 1.16 to 1.62), and peripheral arterial disease (1.35; 1.23 to 1.48), but a lower risk of myocardial infarction (0.88, 0.79 to 1.00) or stable angina (0.93, 0.86 to 1.00). Conclusions  Heterogeneous associations exist between level of alcohol consumption and the initial presentation of cardiovascular diseases. This has implications for counselling patients, public health communication, and clinical research, suggesting a more nuanced approach to the role of alcohol in prevention of cardiovascular disease is necessary. Registration  clinicaltrails.gov (NCT01864031). 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.

Evaluation of children with lymphatic malformations of the head and neck using the Cologne Disease Score.

PubMed

Wiegand, Susanne; Eivazi, Behfar; Zimmermann, Annette P; Sesterhenn, Andreas M; Werner, Jochen A

2009-07-01

To assess the disease-related impairments of children with lymphatic malformations of the head and neck and their changes after therapy using the Cologne Disease Score (CDS). 29 children with lymphatic malformations of the head and neck were evaluated regarding their symptoms before and after therapy using the CDS. The Wilcoxon test for dependent groups was used to compare the CDS at initial visit before treatment and last visit after treatment. The CDS of patients belonging to the moderate (initial CDS: more than eight points) and advanced disease group (initial CDS: five, six or seven points) significantly increased after therapy while the patients in the severe disease group (initial CDS: lower than four points) showed no significant improvement of CDS. Patients with stage IV and especially stage V lymphatic malformations according to de Serres showed considerably lower pre- and posttherapeutic CDS levels than those of stage I and II. The visual impairment is not mapped by the CDS, therefore item vision should be added to the CDS to make an evaluation of all lymphatic malformations of the head and neck possible. The present series could show that especially patients with a moderate or advanced disease according to the CDS may profit from therapeutic interventions.

Characterization of Patients with Amyotrophic Lateral Sclerosis attending the Muscular Dystrophy Association-Supported Clinics in Puerto Rico.

PubMed

Deliz, Brenda; Ramos, Kathya; Pérez, Cynthia M

2018-03-01

To evaluate the sociodemographic characteristics and clinical and functional profile of amyotrophic lateral sclerosis (ALS) patients evaluated at Puerto Rico's Muscular Dystrophy Association-supported (MDA) clinics. A retrospective review of 76 medical records of ALS patients evaluated at any of four MDA-sponsored clinics in Puerto Rico. The mean age of diagnosis was 57.4 ± 11.1 yrs. Most of the patients (52.3%) were women. The majority of the cases were sporadic (48.7%). Over 40% of the patients were diagnosed at one year or earlier. Patients with initial upper extremity involvement (63.2%) were diagnosed earlier (≤ 6 months) than any of the others. The most common presentation of the disease overall was lower extremity weakness (34.2%), which was followed by a bulbar presentation (31.6%). There was a marked difference between men and women in disease presentation, with bulbar involvement in 75% of the women. This study characterized a sample of ALS patients in Puerto Rico who are receiving services at the MDA-sponsored clinics. Puerto Rican patients have similarities with published data from the United States and other countries, including: sporadic pattern, initial symptoms in extremities, and time to diagnosis. Major differences are that the disease was more common in women than in men and that a higher than expected percentage of patients presented with bulbar onset. This may partly account for the overall predominance of the disease in women over men as found in our study, since the bulbar presentation has been reported to be more common in women. Studies with a greater number of patients are needed to determine whether our findings are reproducible. This study will serve as a basis for designing future analytic studies regarding etiology or the factors that might modulate disease progression.

Cost-effectiveness of alternative test strategies for the diagnosis of coronary artery disease.

PubMed

Garber, A M; Solomon, N A

1999-05-04

The appropriate roles for several diagnostic tests for coronary disease are uncertain. To evaluate the cost-effectiveness of alternative approaches to diagnosis of coronary disease. Meta-analysis of the accuracy of alternative diagnostic tests plus decision analysis to assess the health outcomes and costs of alternative diagnostic strategies for patients at intermediate pretest risk for coronary disease. Studies of test accuracy that met inclusion criteria; published information on treatment effectiveness and disease prevalence. Men and women 45, 55, and 65 years of age with a 25% to 75% pretest risk for coronary disease. 30 years. Societal. Diagnostic strategies were initial angiography and initial testing with one of five noninvasive tests--exercise treadmill testing, planar thallium imaging, single-photon emission computed tomography (SPECT), stress echocardiography, and positron emission tomography (PET)--followed by coronary angiography if noninvasive test results were positive. Testing was followed by observation, medical treatment, or revascularization. Life-years, quality-adjusted life-years (QALYs), costs, and costs per QALY. Life expectancy varied little with the initial diagnostic test; for a 55-year-old man, the best-performing test increased life expectancy by 7 more days than the worst-performing test. More sensitive tests increased QALYs more. Echocardiography improved health outcomes and reduced costs relative to stress testing and planar thallium imaging. The incremental cost-effectiveness ratio was $75,000/QALY for SPECT relative to echocardiography and was greater than $640,000 for PET relative to SPECT. Compared with SPECT, immediate angiography had an incremental cost-effectiveness ratio of $94,000/QALY. Qualitative findings varied little with age, sex, pretest probability of disease, or the test indeterminancy rate. Results varied most with sensitivity to severe coronary disease. Echocardiography, SPECT, and immediate angiography are cost-effective alternatives to PET and other diagnostic approaches. Test selection should reflect local variation in test accuracy.

Ischemic diabetic retinopathy as a possible prognostic factor for chronic kidney disease progression

PubMed Central

Lee, W J; Sobrin, L; Kang, M H; Seong, M; Kim, Y J; Yi, J-H; Miller, J W; Cho, H Y

2014-01-01

Purpose To assess the value of diabetic retinopathy (DR) severity as a possible predictive prognostic factor for the progression of chronic kidney disease (CKD). Patients and methods Retrospective cohort study. Patients (51) who were initially diagnosed with DR and CKD were enrolled and their medical records were evaluated. The following ophthalmic factors were assessed by fluorescein angiography at the initial visit: area of capillary nonperfusion, presence of neovascularization and vitreous hemorrhage, and DR grade. The effect of these factors on CKD progression over the 2-year period of the study, defined as doubling of serum creatinine or the development of end-stage renal disease requiring dialysis or renal transplant, was evaluated. Results The study included 51 patients with DR and CKD; of these, 11 patients (21.6%) were found to have proliferative DR (PDR) and seven patients (13.7%) had high-risk PDR at baseline. Patients with ischemic DR, who showed extensive capillary nonperfusion (≥10 optic disc areas) in the retina, had a greater risk for CKD progression (hazard ratio=6.64; P=0.002). Conclusion We found that extensive capillary nonperfusion in the retina greatly increased the risk of progression of CKD in patients with DR. This suggests that the retina and the kidney may have shared risk factors for microvascular disease secondary to diabetes mellitus, and emphasizes the need for a team approach to diabetes care. PMID:24993319

Understanding Autoimmunity of Vitiligo and Alopecia Areata

PubMed Central

Rork, Jillian F.; Rashighi, Mehdi; Harris, John E.

2016-01-01

Purpose of review Vitiligo and alopecia areata are common, disfiguring skin diseases. Treatment options are limited and include non-targeted approaches such as corticosteroids, topical calcineurin inhibitors, narrow band UVB phototherapy, and other immune-modifying agents. The purpose of this article is to review shared, novel mechanisms between vitiligo and alopecia areata, as well as discuss how they inform the development of future targeted treatments. Recent findings Vitiligo and alopecia areata are both autoimmune diseases, and striking similarities in pathogenesis have been identified at the level of both the innate and adaptive immune system. Increased reactive oxygen species and high cellular stress level have been suggested as the initiating trigger of the innate immune system in both diseases, and genome-wide association studies have implicated risk alleles that influence both innate and adaptive immunity. Most importantly, mechanistic studies in mouse models of vitiligo and alopecia areata have specifically implicated an IFN-γ-driven immune response, including IFN-γ, IFN-γ-induced chemokines, and cytotoxic CD8+ T cells as the main drivers of disease pathogenesis. These recent discoveries may reveal an effective strategy to develop new treatments, and several proof-of-concept clinical studies support this hypothesis. Summary The identification of IFN-γ-driven immune signaling pathways has enabled discoveries of potential new treatments for vitiligo and alopecia areata, and supports initiation of larger clinical trials. PMID:27191524

The lung may play a role in the pathogenesis of rheumatoid arthritis

PubMed Central

Demoruelle, M Kristen; Solomon, Joshua J; Fischer, Aryeh; Deane, Kevin D

2015-01-01

Multiple studies have identified strong associations between the lung and rheumatoid arthritis (RA). Such studies identify a high prevalence of lung disease, both airways and parenchymal disease, in subjects with clinically classifiable RA. It has been suggested that lung disease in RA results from targeting of the lung from circulating autoimmunity or other factors such as medications. However, findings that lung disease, specifically inflammatory airways disease, and lung generation of autoimmunity can be present before the onset of joint symptoms suggest that immune reactions in the lung may be involved in the initial development of RA-related autoimmunity. Herein we review these issues in detail, as well as outline a potential research agenda to understand the natural history of lung involvement in RA and its relation to the overall pathogenesis of RA. PMID:26089988

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

PubMed

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

2010-12-01

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

Sphingolipids in Congenital Diaphragmatic Hernia; Results from an International Multicenter Study

PubMed Central

Snoek, Kitty G.; Reiss, Irwin K. M.; Tibboel, Jeroen; van Rosmalen, Joost; Capolupo, Irma; van Heijst, Arno; Schaible, Thomas; Post, Martin; Tibboel, Dick

2016-01-01

Background Congenital diaphragmatic hernia is a severe congenital anomaly with significant mortality and morbidity, for instance chronic lung disease. Sphingolipids have shown to be involved in lung injury, but their role in the pathophysiology of chronic lung disease has not been explored. We hypothesized that sphingolipid profiles in tracheal aspirates could play a role in predicting the mortality/ development of chronic lung disease in congenital diaphragmatic hernia patients. Furthermore, we hypothesized that sphingolipid profiles differ between ventilation modes; conventional mechanical ventilation versus high-frequency oscillation. Methods Sphingolipid levels in tracheal aspirates were determined at days 1, 3, 7 and 14 in 72 neonates with congenital diaphragmatic hernia, born after > 34 weeks gestation at four high-volume congenital diaphragmatic hernia centers. Data were collected within a multicenter trial of initial ventilation strategy (NTR 1310). Results 36 patients (50.0%) died or developed chronic lung disease, 34 patients (47.2%) by stratification were initially ventilated by conventional mechanical ventilation and 38 patients (52.8%) by high-frequency oscillation. Multivariable logistic regression analysis with correction for side of the defect, liver position and observed-to-expected lung-to-head ratio, showed that none of the changes in sphingolipid levels were significantly associated with mortality /development of chronic lung disease. At day 14, long-chain ceramides 18:1 and 24:0 were significantly elevated in patients initially ventilated by conventional mechanical ventilation compared to high-frequency oscillation. Conclusions We could not detect significant differences in temporal sphingolipid levels in congenital diaphragmatic hernia infants with mortality/development of chronic lung disease versus survivors without development of CLD. Elevated levels of ceramides 18:1 and 24:0 in the conventional mechanical ventilation group when compared to high-frequency oscillation could probably be explained by high peak inspiratory pressures and remodeling of the alveolar membrane. PMID:27159222

Primary cutaneous marginal zone B-cell lymphoma: response to treatment and disease-free survival in a series of 137 patients.

PubMed

Servitje, Octavio; Muniesa, Cristina; Benavente, Yolanda; Monsálvez, Verónica; Garcia-Muret, M Pilar; Gallardo, Fernando; Domingo-Domenech, Eva; Lucas, Anna; Climent, Fina; Rodriguez-Peralto, Jose L; Ortiz-Romero, Pablo L; Sandoval, Juan; Pujol, Ramon M; Estrach, M Teresa

2013-09-01

Primary cutaneous marginal zone B-cell lymphomas are low-grade lymphomas running an indolent course. Skin relapses have been frequently reported but little information about disease-free survival (DFS) is available. We sought to evaluate relapse rate and DFS in patients with primary cutaneous marginal zone B-cell lymphomas. Clinical features, European Organization for Research and Treatment of Cancer/International Society for Cutaneous Lymphomas stage, light chain restriction, clonality, treatments, skin relapses, DFS, stage progression, extracutaneous disease, and outcome are analyzed in a series of 137 patients. Patients were classified as solitary lesion (T1) (n = 70; 51%), regional skin involvement (T2) (n = 40; 29%), and generalized skin lesions (T3) (n = 27; 20%). Surgical excision, local radiotherapy, or a combination were the initial treatment in 118 patients (86%). In 121 of 137 patients (88%) a complete remission was observed after initial treatment, including 99 of 106 patients (93%) with solitary or localized disease and 22 of 31 patients (71%) with multifocal lesions. Cutaneous relapses were observed in 53 patients (44%). Median DFS was 47 months. Patients with multifocal lesions or T3 disease showed higher relapse rate and shorter DFS. No significant differences were observed between surgery and radiotherapy, but surgery alone was associated with more recurrences at initial site. Overall survival at 5 and 10 years was 93%. Six patients (4%) developed extracutaneous disease during follow-up. This was a case series retrospective study. Our results support long-term follow-up in patients with primary cutaneous marginal zone B-cell lymphomas. Disseminated skin lesions have higher relapse rate and shorter DFS suggesting further investigation on systemic therapies in such a group of patients. Copyright © 2013 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.

Prevalence and Prognosis of Cerebrovascular Accidents and its Subtypes Among Patients with Systemic Lupus Erythematosus in Isfahan, Iran: A Hospital Clinic-based Study.

PubMed

Saadatnia, Mohammad; Sayed-Bonakdar, Zahra; Mohammad-Sharifi, Ghasem; Sarrami, Amir Hossein

2014-01-01

The aim of the present study was to determine the prevalence and prognosis of cerebrovascular accident (CVA) and its subtypes among Iranian patients with systemic lupus erythematosus (SLE). In a cross-sectional study, medical records of 575 SLE patients were reviewed. The patients developing CVA in their course of disease were extracted. In these patients, data about demographic features, lupus anti bodies, duration of the disease until CVA, CVA manifestation(s) and follow-up duration were gathered. In the next step, patients with any kinds of CVA were summoned to Neurology clinic to identify the grade of disability in each patient with CVA. We identified 38 patients with CVA of which 6 (15.8%) were men and 32 (84.2%) were women. The most common subtype of CVA was small vessels thrombosis (21.05%) among the study patients and hemi paresis was the most prevalent initial presentation (39.47%). In 11 (28.9%) patients, SLE was initiated with CVA and in 3 (7.9%) patients CVA had happened in the 1(st) year of SLE. Anti-phospholipid antibodies (APLA) were positive in 29 (76.3%) patients. Mean modified Rankin Scale in patient with positive and negative serology for APLA was 0.93 ± 1.11 and 0.22 ± 0.66 respectively (P = 0.006). Our study shows that 6.6% of Iranian SLE patients have CVA during their course of the disease. Small vessels thrombosis is the most common CVA subtype and hemi paresis is the most prevalent initial presentation. Moreover, we showed that the prognosis of CVA in Iranian SLE patients is not unfavorable.

The Impact of Therapeutic Antibodies on the Management of Digestive Diseases: History, Current Practice, and Future Directions.

PubMed

Sofia, M Anthony; Rubin, David T

2017-04-01

The development of therapeutic antibodies represents a revolutionary change in medical therapy for digestive diseases. Beginning with the initial studies that confirmed the pathogenicity of cytokines in inflammatory bowel disease, the development and application of therapeutic antibodies brought challenges and insights into their potential and optimal use. Infliximab was the first biological drug approved for use in Crohn's disease and ulcerative colitis. The lessons learned from infliximab include the importance of immunogenicity and the influence of pharmacokinetics on disease response and outcomes. Building on this foundation, other therapeutic antibodies achieved approval for inflammatory bowel disease and many more are in development for several digestive diseases. In this review, we reflect on the history of therapeutic antibodies and discuss current practice and future directions for the field.

Natural History of Rotator Cuff Disease and Implications on Management

PubMed Central

Hsu, Jason

2015-01-01

Degenerative rotator cuff disease is commonly associated with ageing and is often asymptomatic. The factors related to tear progression and pain development are just now being defined through longitudinal natural history studies. The majority of studies that follow conservatively treated painful cuff tears or asymptomatic tears that are monitored at regular intervals show slow progression of tear enlargement and muscle degeneration over time. These studies have highlighted greater risks for disease progression for certain variables, such as the presence of a full-thickness tear and involvement of the anterior aspect supraspinatus tendon. Coupling the knowledge of the natural history of degenerative cuff tear progression with variables associated with greater likelihood of successful tendon healing following surgery will allow better refinement of surgical indications for rotator cuff disease. In addition, natural history studies may better define the risks of nonoperative treatment over time. This article will review pertinent literature regarding degenerative rotator cuff disease with emphasis on variables important to defining appropriate initial treatments and refining surgical indications. PMID:26726288

Role of the fixed combination of fluticasone and salmeterol in adult Chinese patients with asthma and COPD

PubMed Central

Gao, Jinming; Pleasants, Roy A

2015-01-01

Chronic obstructive pulmonary disease (COPD) and asthma are common airway disorders characterized by chronic airway inflammation and airflow obstruction, and are a leading cause of morbidity and mortality in the People’s Republic of China. These two diseases pose a high economic burden on the family and the whole of society. Despite evidence-based Global Initiative for Chronic Obstructive Lung Disease and Global Initiative for Asthma guidelines being available for the diagnosis and management of COPD and asthma, many of these patients are not properly diagnosed or managed in the People’s Republic of China. The value of combination therapy with inhaled corticosteroids and long-acting β2-agonists has been established in the management of asthma and COPD globally. Combinations of inhaled corticosteroids and long-acting β2-agonists such as fluticasone and salmeterol, have been shown to be effective for improving symptoms, health status, and reducing exacerbations in both diseases. In this review, we discuss the efficacy and safety of this combination therapy from key studies, particularly in the People’s Republic of China. PMID:25926729

Community-based Early Warning and Adaptive Response System (EWARS) for mosquito borne diseases: An open source/open community approach

NASA Astrophysics Data System (ADS)

Babu, A. N.; Soman, B.; Niehaus, E.; Shah, J.; Sarda, N. L.; Ramkumar, P. S.; Unnithan, C.

2014-11-01

A variety of studies around the world have evaluated the use of remote sensing with and without GIS in communicable diseases. The ongoing Ebola epidemic has highlighted the risks that can arise for the global community from rapidly spreading diseases which may outpace attempts at control and eradication. This paper presents an approach to the development, deployment, validation and wide-spread adoption of a GIS-based temporo-spatial decision support system which is being collaboratively developed in open source/open community mode by an international group that came together under UN auspices. The group believes in an open source/open community approach to make the fruits of knowledge as widely accessible as possible. A core initiative of the groups is the EWARS project. It proposes to strengthen existing public health systems by the development and validation a model for a community based surveillance and response system which will initially address mosquito borne diseases in the developing world. At present mathematical modeling to support EWARS is at an advanced state, and it planned to embark on a pilot project

Evaluation of the Centers for Disease Control and Prevention's Concussion Initiative for High School Coaches: "Heads up: Concussion in High School Sports"

ERIC Educational Resources Information Center

Sarmiento, Kelly; Mitchko, Jane; Klein, Cynthia; Wong, Sharon

2010-01-01

Background: To reduce the number of sports-related concussions, the Centers for Disease Control and Prevention (CDC), with the support of partners and experts in the field, has developed a tool kit for high school coaches with practical, easy-to-use concussion-related information. This study explores the success of the tool kit in changing…

Regular Exercise and Plasma Lipid Levels Associated with the Risk of Coronary Heart Disease: A 20-Year Longitudinal Study

ERIC Educational Resources Information Center

Teramoto, Masaru; Golding, Lawrence A.

2009-01-01

We investigated the effects of regular exercise on the plasma lipid levels that contribute to coronary heart disease (CHD), of 20 sedentary men who participated in an exercise program over 20 consecutive years. The men, whose initial ages ranged from 30-51 years, participated in the University of Nevada-based exercise program for an average of 45…

Relation of Salivary PAF Periodontal Disease in Periodontal Maintenance and Refractory Periodontitis Patients

DTIC Science & Technology

1991-05-01

Knox, 1974). Studies have demonstrated the presence of streptococci and lactobacilli throughout the oral cavity , as well as in developing dental... oral cavity , it is apparent that these compounds have the potential to play a role in the initiation and progression of inflammatory oral disease...junctional epithelium and into the gingival sulcus and oral cavity . The perivascular connective tissue matrix becomes altered most likely by

LONGITUDINAL FOLLOW-UP OF LATE-ONSET ALZHEIMER DISEASE FAMILIES

PubMed Central

Carney, R.M.; Slifer, M.A.; Lin, P.I.; Gaskell, P. C.; Scott, W. K.; Potocky, C.F.; Hulette, C. M.; Welsh-Bohmer, K. A.; Schmechel, D. E.; Vance, J.M.; Pericak-Vance, M. A.

2009-01-01

Historically, data for genetic studies are collected at one time point. However, for diseases with late onset or with complex phenotypes, such as Alzheimer disease (AD), restricting diagnosis to a single ascertainment contact may not be sufficient. Affection status may change over time, and some initial diagnoses may be inconclusive. Follow-up provides the opportunity to resolve these complications. However, to date, previous studies have not formally demonstrated that longitudinally re-contacting families is practical or productive. To update data initially collected for linkage analysis of late-onset Alzheimer disease (LOAD), we successfully re-contacted 63 of 81 (78%) multiplex families (two to 17 years after ascertainment). Clinical status changed for 73 of the 230 (32%) non-affected participants. Additionally, expanded family history identified 20 additional affected individuals to supplement the data set. Furthermore, fostering ongoing relationships with participating families helped recruit 101 affected participants into an autopsy and tissue donation program. Despite similar presentations, discordance between clinical diagnosis and neuropathologic diagnosis was observed in 28% of those with tissue diagnoses. Most of the families were successfully re-contacted, and significant refinement and supplementation of the data was achieved. We concluded that serial contact with longitudinal evaluation of families has significant implications for genetic analyses. PMID:18361431

Fabry disease in children: agalsidase-beta enzyme replacement therapy.

PubMed

Borgwardt, L; Feldt-Rasmussen, U; Rasmussen, A K; Ballegaard, M; Meldgaard Lund, A

2013-05-01

Fabry disease is a rare, multiorgan disease. The most serious complications involve the kidney, brain and heart. This study aims to assess the effect of enzyme replacement therapy (ERT) using agalsidase-beta in children with Fabry disease. We carried out a nationwide, descriptive and observational retrospective cohort study of 10 children (9-16 years at baseline), who underwent regular systematic investigations for 1-8 years after initiation of ERT with agalsidase-beta (Fabryzyme®, Genzyme). Ophthalmological, echocardiographic abnormalities and hypohidrosis were found at baseline and during the follow-up period. Serious kidney, heart or brain involvement had not developed at the last follow-up examination. For the majority of the patients improvements were found concerning headache, acroparaesthesias and gastrointestinal pain during the follow-up period. The level of energy and physical activity also increased. Treatment with agalsidase-beta was associated with a reduction of neuropathic and abdominal pain and headache. Although all aspects of the Fabry pain phenotype cannot be treated with ERT, the observed effects were clinically significant in the lives of the majority of Fabry children and together with the absence of serious Fabry manifestations at last follow-up, we argue that early initiation of ERT may be considered. © 2012 John Wiley & Sons A/S.

Exploring the multifunctionality of thioflavin- and deferiprone-based molecules as acetylcholinesterase inhibitors for potential application in Alzheimer's disease.

PubMed

Telpoukhovskaia, Maria A; Patrick, Brian O; Rodríguez-Rodríguez, Cristina; Orvig, Chris

2013-04-05

Alzheimer's disease (AD) is a devastating neurodegenerative disease that affects millions of people worldwide. With no prevention or cure available, this progressive disease has a significant impact on society - dementia patients and their caretakers, healthcare systems, and the economy. Previously, we have reported initial developments of multifunctional drug candidates for AD based on two scaffolds - thioflavin-T and deferiprone. Individually, these molecules have shown several favorable functionalities, including dissociation of toxic amyloid-β aggregates, antioxidant and/or metal chelating ability that can pacify reactive oxygen species, plaque targeting, and blood-brain barrier penetration. In this work, the two scaffolds are augmented with a new functionality - acetylcholinesterase inhibition. This functionality is incorporated by derivatization with a carbamate group, which is the active group in some AD drugs currently in the market. We present the rationale for designing three novel compounds, their synthesis and characterization, including X-ray crystallographic data, and encouraging results from in vitro and computational acetylcholinesterase inhibition studies. Also, we evaluate the compounds as potential drug candidates by Lipinski's rules and cytotoxicity studies in a neuronal cell line. Overall, we demonstrate the feasibility of improving on two well established scaffolds, as well as show in vitro efficacy plus initial mode of action and biological compatibility data.

THE MITOCHONDRIAL PARADIGM FOR CARDIOVASCULAR DISEASE SUSCEPTIBILITY AND CELLULAR FUNCTION: A COMPLEMENTARY CONCEPT TO MENDELIAN GENETICS

PubMed Central

Kryzwanski, David M.; Moellering, Douglas; Fetterman, Jessica L.; Dunham-Snary, Kimberly J.; Sammy, Melissa J.; Ballinger, Scott W.

2013-01-01

While there is general agreement that cardiovascular disease (CVD) development is influenced by a combination of genetic, environmental, and behavioral contributors, the actual mechanistic basis of how these factors initiate or promote CVD development in some individuals while others with identical risk profiles do not, is not clearly understood. This review considers the potential role for mitochondrial genetics and function in determining CVD susceptibility from the standpoint that the original features that molded cellular function were based upon mitochondrial-nuclear relationships established millions of years ago and were likely refined during prehistoric environmental selection events that today, are largely absent. Consequently, contemporary risk factors that influence our susceptibility to a variety of age-related diseases, including CVD were probably not part of the dynamics that defined the processes of mitochondrial – nuclear interaction, and thus, cell function. In this regard, the selective conditions that contributed to cellular functionality and evolution should be given more consideration when interpreting and designing experimental data and strategies. Finally, future studies that probe beyond epidemiologic associations are required. These studies will serve as the initial steps for addressing the provocative concept that contemporary human disease susceptibility is the result of selection events for mitochondrial function that increased chances for prehistoric human survival and reproductive success. PMID:21647091

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.

The Genetics of Autoimmune Thyroiditis: the first decade

PubMed Central

Rose, Noel R.

2011-01-01

Most of our current understanding of the genetic predisposition to autoimmune disease can be traced to experiments performed in the decade from 1971 to 1981. Chella David was a key contributor to this research. Many of these early steps came from studies of experimental autoimmune thyroiditis. This model has been especially valuable because essentially the same disease can occur spontaneously in selected strains of animals or can be induced by deliberate immunization. From a genetic point of view, the disease has been investigated in three different species: mice, rats and chickens. The same antigen, thyroglobulin, initiates the disease in all three species. Among the main discoveries were the relationship of autoimmune disease to the major histocompatibility complex (MHC), the interplay of different subregions within the MHC in promoting or retarding development of disease, the differing roles of MHC class II and MHC I class genes in induction and effector phases, respectively, and the cumulative effect of non-MHC genes, each of which represents a small addition to overall susceptibility. Other experiments revealed that genetic differences in thyroglobulin allotypes influence susceptibility to thyroiditis. Thyroid glands differed in different strains in vulnerability to passive transfer of antibody. The first evidence of modulatory genes on the sex-related X chromosome emerged. All of these genetic findings were concurrently translated to the human disease, Hashimoto’s thyroiditis, where thyroglobulin is also the initiating antigen. PMID:21683550

Timely Diagnosis for Alzheimer's Disease: A Literature Review on Benefits and Challenges.

PubMed

Dubois, Bruno; Padovani, Alessandro; Scheltens, Philip; Rossi, Andrea; Dell'Agnello, Grazia

2016-01-01

Timely diagnosis of Alzheimer's disease (AD) refers to a diagnosis at the stage when patients come to the attention of clinicians because of concerns about changes in cognition, behavior, or functioning and can be still free of dementia and functionally independent. To comprehensively review existing scientific evidence on the benefits and potential challenges of making a timely diagnosis of AD. Relevant studies were identified by searching electronic databases (Medline, Embase) and bibliographies for studies published in English between 1 January 2000 and 2 June 2014 on the consequences of a timely diagnosis of AD. Nine studies were identified that investigated the consequences of diagnosing AD at the initial stages; none were specifically focused on prodromal AD. A timely diagnosis potentially offers the opportunities of early intervention, implementation of coordinated care plans, better management of symptoms, patient safety, cost savings, and postponement of institutionalization. Barriers to making a timely diagnosis include stigma, suicide risk, lack of training, diagnostic uncertainty, shortage of specialized diagnostic services, and the reluctance of healthcare providers to make a diagnosis when no effective disease-modifying options are available. Despite its potential benefits, few published studies have explored the advantages or risks of a timely diagnosis of AD. In light of the cultural shift toward diagnosis at the initial stage of the disease continuum, when the patient does not yet have dementia, more investigations are needed to evaluate the benefits and address the barriers that may impede making a timely AD diagnosis.

Is higher income and educational status associated with poorer outcome in patients with Hodgkin's disease?

PubMed

Holzner, Bernhard; Fischhofer, Martina; Kemmler, Georg; Kopp, Martin; Sperner-Unterweger, Barbara; Krugmann, Jens; Dirnhofer, Stephan; Greil, Richard

2004-11-01

The aim of the study was to determine the impact of socioeconomic status on relapse-free survival (RFS) in patients with Hodgkin's disease. A number of factors were analyzed for their impact on relapse-free and overall survival in Hodgkin's disease using Cox regression. These factors included socioeconomic status (as defined by education and income), different treatment modalities and established clinical risk factors [e.g. age at diagnosis, stage of disease, involvement of three or more lymph nodes, presence or absence of a large mediastinal mass, E stages or elevation of erythrocyte sedimentation rate (ESR)]. The study used an initial sample of 126 patients recruited between 1969 and 1995 and a larger sample of 218 patients (recruited until 2002). Clinical data on disease and treatment characteristics were collected from medical records. In a univariate analysis, the following parameters had impact on RFS: treatment modality (combined treatment resulted in an improved RFS compared with patients treated with chemo- or radiotherapy alone), educational status and income. The 5- and 10-yr relapse-free survival rates were found to increase with decreasing educational level and decreasing average income per month. These results were significant in the initial and total samples and were also significant using multivariate analysis (hazard ratio for highest vs. lowest education group: 5.88; 95% confidence interval 1.87-18.52; for highest vs. lowest income group: 4.36; 95% confidence interval 1.35-14.05). Hodgkin's disease appears to be a striking exception from the usual positive correlation between high socioeconomic status and favorable treatment outcome in patients suffering from tumor. It is suggested that future studies on tumor genetics and biology and more detailed analysis of further socioeconomic parameters may be useful in clarifying this observation.

Emergence of Persistent Infection due to Heterogeneity

NASA Astrophysics Data System (ADS)

Agrawal, Vidit; Moitra, Promit; Sinha, Sudeshna

2017-02-01

We explore the emergence of persistent infection in a closed region where the disease progression of the individuals is given by the SIRS model, with an individual becoming infected on contact with another infected individual. We investigate the persistence of contagion qualitatively and quantitatively, under increasing heterogeneity in the partitioning of the population into different disease compartments, as well as increasing heterogeneity in the phases of the disease among individuals within a compartment. We observe that when the initial population is uniform, consisting of individuals at the same stage of disease progression, infection arising from a contagious seed does not persist. However when the initial population consists of randomly distributed refractory and susceptible individuals, a single source of infection can lead to sustained infection in the population, as heterogeneity facilitates the de-synchronization of the phases in the disease cycle of the individuals. We also show how the average size of the window of persistence of infection depends on the degree of heterogeneity in the initial composition of the population. In particular, we show that the infection eventually dies out when the entire initial population is susceptible, while even a few susceptibles among an heterogeneous refractory population gives rise to a large persistent infected set.

Timing of dialysis initiation, duration and frequency of hemodialysis sessions, and membrane flux: a systematic review for a KDOQI clinical practice guideline.

PubMed

Slinin, Yelena; Greer, Nancy; Ishani, Areef; MacDonald, Roderick; Olson, Carin; Rutks, Indulis; Wilt, Timothy J

2015-11-01

In 2006, NKF-KDOQI (National Kidney Foundation-Kidney Disease Outcomes Quality Initiative) published clinical practice guidelines for hemodialysis adequacy. Recent studies evaluating hemodialysis adequacy as determined by initiation timing, frequency, duration, and membrane type and prompted an update to the guideline. Systematic review and evidence synthesis. Patients with advanced chronic kidney disease receiving hemodialysis. We screened publications from 2000 to March 2014, systematic reviews, and references and consulted the NKF-KDOQI Hemodialysis Adequacy Work Group members. We included randomized or controlled clinical trials in patients undergoing long-term hemodialysis if they reported outcomes of interest. Early versus late dialysis therapy initiation; more frequent (>3 times a week) or longer duration (>4.5 hours) compared to conventional hemodialysis; low- versus high-flux dialyzer membranes. All-cause and cardiovascular mortality, myocardial infarction, stroke, hospitalizations, quality of life, depression or cognitive function scores, blood pressure, number of antihypertensive medications, left ventricular mass, interdialytic weight gain, and harms or complications related to vascular access or the process of dialysis. We included 32 articles reporting on 19 trials. Moderate-quality evidence indicated that earlier dialysis therapy initiation (at estimated creatinine clearance [eClcr] of 10-14mL/min) did not reduce mortality compared to later initiation (eClcr of 5-7mL/min). More than thrice-weekly hemodialysis and extended-length hemodialysis during a short follow-up did not improve clinical outcomes compared to conventional hemodialysis and resulted in a greater number of vascular access procedures (very low-quality evidence). Hemodialysis using high-flux membranes did not reduce all-cause mortality, but reduced cardiovascular mortality compared to hemodialysis using low-flux membranes (moderate-quality evidence). Few studies were adequately powered to evaluate mortality. Heterogeneity of study designs and interventions precluded pooling data for most outcomes. Limited data indicate that earlier dialysis therapy initiation and more frequent and longer hemodialysis did not improve clinical outcomes compared to conventional hemodialysis. Published by Elsevier Inc.

The California Clinical Data Project: a case study in the adoption of clinical data standards for quality improvement.

PubMed

Sujansky, Walter; Chang, Sophia

2006-01-01

The California Clinical Data Project is a statewide initiative to remove barriers to the widespread and effective use of information technology to improve chronic disease care. The project is a case study in the development and widespread adoption of clinical data standards by varied and often competing stakeholders. As an initial step, the project defined precise data standards for the batch reporting of pharmacy claims data and laboratory results data. These uniform standards facilitate the flow of existing electronic clinical information into disease registries and electronic health record systems. Pharmacy and lab results data now are being exchanged electronically with this standard among the largest health plans, medical groups, and clinical laboratories participating in California's pay-for-performance programs. Lessons from this project may apply to the development and adoption of data standards for other states and locales and for the emerging national health information infrastructure.

Pyrogen release in vitro by lymphoid tissues from patients with Hodgkin's disease.

PubMed

Bodel, P

1974-01-01

The mechanism of fever in patients with Hodgkin's disease was investigated by examining endogenous pyrogen production by blood, spleen, and lymph node cells incubated in vitro. Blood leucocytes from febrile or afebrile patients with Hodgkin's disease did not produce pyrogen spontaneously. Spleen cells, however, frequently released pyrogen during initial incubations, unlike spleen cells from patients with non-malignant diseases. Pyrogen production occurred from spleens without observed pathologic infiltrates of Hodgkin's disease. Lymph nodes involved with Hodgkin's disease produced pyrogen more frequently than did nodes involved with other diseases. Pyrogen production by tissue cells was prolonged, required protein synthesis, and in some cases was due to mononuclear cells; it did not correlate with fever in the patient. These studies demonstrate spontaneous production of endogenous pyrogen in vitro by lymphoid tissue cells from patients with Hodgkin's disease.

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.

Economic evaluation of a pre-ESRD pay-for-performance programme in advanced chronic kidney disease patients.

PubMed

Hsieh, Hui-Min; Lin, Ming-Yen; Chiu, Yi-Wen; Wu, Ping-Hsun; Cheng, Li-Jeng; Jian, Feng-Shiuan; Hsu, Chih-Cheng; Hwang, Shang-Jyh

2017-07-01

The National Health Insurance Administration in Taiwan initiated a nationwide pre-end-stage renal disease (ESRD) pay-for-performance (P4P) programme at the end of 2006 to improve quality of care for chronic kidney disease (CKD) patients. This study aimed to examine this programme's effect on patients' clinical outcomes and its cost-effectiveness among advanced CKD patients. We conducted a longitudinal observational matched cohort study using two nationwide population-based datasets. The major outcomes of interests were incidence of dialysis, all-cause mortality, direct medical costs, life years (LYs) and incremental cost-effectiveness ratio comparing matched P4P and non-P4P advanced CKD patients. Competing-risk analysis, general linear regression and bootstrapping statistical methods were used for the analysis. Subdistribution hazard ratio (95% confidence intervals) for advanced CKD patients enrolled in the P4P programme, compared with those who did not enrol, were 0.845 (0.779-0.916) for incidence of dialysis and 0.792 (0.673-0.932) for all-cause mortality. LYs for P4P and non-P4P patients who initiated dialysis were 2.83 and 2.74, respectively. The adjusted incremental CKD-related costs and other-cause-related costs were NT$114 704 (US$3823) and NT$32 420 (US$1080) for P4P and non-P4P patients who initiated dialysis, respectively, and NT$-3434 (US$114) and NT$45 836 (US$1572) for P4P and non-P4P patients who did not initiate dialysis, respectively, during the 3-year follow-up period. P4P patients had lower risks of both incidence of dialysis initiation and death. In addition, our empirical findings suggest that the P4P pre-ESRD programme in Taiwan provided a long-term cost-effective use of resources and cost savings for advanced CKD patients. © The Author 2016. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

Pattern and predictors of the initiation of biologic agents for the treatment of rheumatoid arthritis in the United States: an analysis using a large observational data bank.

PubMed

DeWitt, Esi Morgan; Lin, Li; Glick, Henry A; Anstrom, Kevin J; Schulman, Kevin A; Reed, Shelby D

2009-08-01

The aim of this study was to identify factors associated with the initiation of biologic agents for the treatment of rheumatoid arthritis (RA) in a large US observational cohort. Semiannual patient-reported data in the ARAMIS (Arthritis, Rheumatism and Aging Medical Information System) data bank from January 1998 to January 2006 were analyzed retrospectively using pooled logistic regression (with adjustment for center-level and temporal effects) to identify patient-, disease-, and treatment-related characteristics associated with the initiation of biologics for the treatment of RA. The analysis included 1545 patients from 7 US centers. By 2006, 41.4% of 679 patients remaining in the sample had received biologics. Initiation of biologics was significantly associated with greater disability in the previous 6-month period (per 1-unit increase in Health Assessment Questionnaire score: odds ratio [OR] = 1.45; 95% CI, 1.22-1.72; P < 0.01) and treatment in the previous period with steroids (OR = 2.24; 95% CI, 1.76-2.85; P < 0.01) or nonbiologic disease-modifying antirheumatic drugs (OR = 2.43; 95% CI, 1.71-3.46; P < 0.01). Two sociodemographic factors were significant predictors of decreased use of biologics: older age (per 10 years: OR = 0.74; 95% CI, 0.660.82; P < 0.01) and lower annual income (per $10,000 reduction: OR = 0.95; 95% CI, 0.91-1.00; P = 0.04). There were no significant differences with respect to sex, race, employment status, comorbidity, previous NSAID use, or treatment center. Disease- and treatment-related factors were significant predictors of the initiation of biologics for RA. Independent of these factors, however, biologics were less often used in patients who were older and those with lower incomes. Use of biologics increased steadily over the period studied.

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

Survival after initial diagnosis of Alzheimer disease.

PubMed

Larson, Eric B; Shadlen, Marie-Florence; Wang, Li; McCormick, Wayne C; Bowen, James D; Teri, Linda; Kukull, Walter A

2004-04-06

Alzheimer disease is an increasingly common condition in older people. Knowledge of life expectancy after the diagnosis of Alzheimer disease and of associations of patient characteristics with survival may help planning for future care. To investigate the course of Alzheimer disease after initial diagnosis and examine associations hypothesized to correlate with survival among community-dwelling patients with Alzheimer disease. Prospective observational study. An Alzheimer disease patient registry from a base population of 23 000 persons age 60 years and older in the Group Health Cooperative, Seattle, Washington. 521 newly recognized persons with Alzheimer disease enrolled from 1987 to 1996 in an Alzheimer disease patient registry. Baseline measurements included patient demographic features, Mini-Mental State Examination score, Blessed Dementia Rating Scale score, duration since reported onset of symptoms, associated symptoms, comorbid conditions, and selected signs. Survival was the outcome of interest. The median survival from initial diagnosis was 4.2 years for men and 5.7 years for women with Alzheimer disease. Men had poorer survival across all age groups compared with females. Survival was decreased in all age groups compared with the life expectancy of the U.S. population. Predictors of mortality based on proportional hazards models included a baseline Mini-Mental State Examination score of 17 or less, baseline Blessed Dementia Rating Scale score of 5.0 or greater, presence of frontal lobe release signs, presence of extrapyramidal signs, gait disturbance, history of falls, congestive heart failure, ischemic heart disease, and diabetes at baseline. The base population, although typical of the surrounding Seattle community, may not be representative of other, more diverse populations. In this sample of community-dwelling elderly persons who received a diagnosis of Alzheimer disease, survival duration was shorter than predicted on the basis of U.S. population data, especially for persons with onset at relatively younger ages. Features significantly associated with reduced survival at diagnosis were increased severity of cognitive impairment, decreased functional level, history of falls, physical examination findings of frontal release signs, and abnormal gait. The variables most strongly associated with survival were measures of disease severity at the time of diagnosis. These results should be useful to patients and families experiencing Alzheimer disease, other caregivers, clinicians, and policymakers when planning for future care needs.

Chronic behavior disturbance and neurocognitive deficits in neuro-Behcet's disease: a case study.

PubMed

Fisher, Caroline A; Sewell, Katherine; Baker, Amy

2016-06-01

Behcet's disease is a vasculitis and multisystem inflammatory syndrome. Neurological abnormalities occur in a subset of patients. This report presents a case of neuro-Behcet's disease characterized by an initial onset of behavior changes prior to diagnosis, which evolved into a chronic behavioral syndrome. Neuroimaging investigations revealed progressive periventricular white matter and brainstem atrophy and lesions in the basal ganglia and deep white matter tracts, while neuropsychological investigations revealed reductions in information processing, executive functioning, and memory. The case indicates that behavior changes may be the first symptoms to emerge in Behcet's, before other defining features of the disease.

75 FR 34458 - National Center for Injury Prevention and Control/Initial Review Group, (NCIPC/IRG)

Federal Register 2010, 2011, 2012, 2013, 2014

2010-06-17

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Centers for Disease Control and Prevention National Center for Injury Prevention and Control/Initial Review Group, (NCIPC/IRG) Correction: This notice was... (Pub. L. 92-463), the Centers for Disease Control and Prevention (CDC), announces the following meeting...

75 FR 34459 - National Center for Injury Prevention and Control/Initial Review Group, (NCIPC/IRG)

Federal Register 2010, 2011, 2012, 2013, 2014

2010-06-17

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Centers for Disease Control and Prevention National Center for Injury Prevention and Control/Initial Review Group, (NCIPC/IRG) Correction: This notice was... (Pub. L. 92-463), the Centers for Disease Control and Prevention (CDC), announces the following meeting...

75 FR 34458 - National Center for Injury Prevention and Control/Initial Review Group, (NCIPC/IRG)

Federal Register 2010, 2011, 2012, 2013, 2014

2010-06-17

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Centers for Disease Control and Prevention National Center for Injury Prevention and Control/Initial Review Group, (NCIPC/IRG) Correction: This notice was... Federal Advisory Committee Act (Pub. L. 92-463), the Centers for Disease Control and Prevention (CDC...

75 FR 34459 - National Center for Injury Prevention and Control/Initial Review Group, (NCIPC/IRG)

Federal Register 2010, 2011, 2012, 2013, 2014

2010-06-17

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Centers for Disease Control and Prevention National Center for Injury Prevention and Control/Initial Review Group, (NCIPC/IRG) Correction: This notice was... Advisory Committee Act (Pub. L. 92-463), the Centers for Disease Control and Prevention (CDC), announces...

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...

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...

Comparative effectiveness studies to improve clinical outcomes in end stage renal disease: the DEcIDE patient outcomes in end stage renal disease study

PubMed Central

2012-01-01

Background Evidence is lacking to inform providers’ and patients’ decisions about many common treatment strategies for patients with end stage renal disease (ESRD). Methods/design The DEcIDE Patient Outcomes in ESRD Study is funded by the United States (US) Agency for Health Care Research and Quality to study the comparative effectiveness of: 1) antihypertensive therapies, 2) early versus later initiation of dialysis, and 3) intravenous iron therapies on clinical outcomes in patients with ESRD. Ongoing studies utilize four existing, nationally representative cohorts of patients with ESRD, including (1) the Choices for Healthy Outcomes in Caring for ESRD study (1041 incident dialysis patients recruited from October 1995 to June 1999 with complete outcome ascertainment through 2009), (2) the Dialysis Clinic Inc (45,124 incident dialysis patients initiating and receiving their care from 2003–2010 with complete outcome ascertainment through 2010), (3) the United States Renal Data System (333,308 incident dialysis patients from 2006–2009 with complete outcome ascertainment through 2010), and (4) the Cleveland Clinic Foundation Chronic Kidney Disease Registry (53,399 patients with chronic kidney disease with outcome ascertainment from 2005 through 2009). We ascertain patient reported outcomes (i.e., health-related quality of life), morbidity, and mortality using clinical and administrative data, and data obtained from national death indices. We use advanced statistical methods (e.g., propensity scoring and marginal structural modeling) to account for potential biases of our study designs. All data are de-identified for analyses. The conduct of studies and dissemination of findings are guided by input from Stakeholders in the ESRD community. Discussion The DEcIDE Patient Outcomes in ESRD Study will provide needed evidence regarding the effectiveness of common treatments employed for dialysis patients. Carefully planned dissemination strategies to the ESRD community will enhance studies’ impact on clinical care and patients’ outcomes. PMID:23217181

Neuromagnetic Index of Hemispheric Asymmetry Prognosticating the Outcome of Sudden Hearing Loss

PubMed Central

Li, Lieber Po-Hung; Shiao, An-Suey; Chen, Kuang-Chao; Lee, Po-Lei; Niddam, David M.; Chang, Shyue-Yih; Hsieh, Jen-Chuen

2012-01-01

The longitudinal relationship between central plastic changes and clinical presentations of peripheral hearing impairment remains unknown. Previously, we reported a unique plastic pattern of “healthy-side dominance” in acute unilateral idiopathic sudden sensorineural hearing loss (ISSNHL). This study aimed to explore whether such hemispheric asymmetry bears any prognostic relevance to ISSNHL along the disease course. Using magnetoencephalography (MEG), inter-hemispheric differences in peak dipole amplitude and latency of N100m to monaural tones were evaluated in 21 controls and 21 ISSNHL patients at two stages: initial and fixed stage (1 month later). Dynamics/Prognostication of hemispheric asymmetry were assessed by the interplay between hearing level/hearing gain and ipsilateral/contralateral ratio (I/C) of N100m latency and amplitude. Healthy-side dominance of N100m amplitude was observed in ISSNHL initially. The pattern changed with disease process. There is a strong correlation between the hearing level at the fixed stage and initial I/Camplitude on affected-ear stimulation in ISSNHL. The optimal cut-off value with the best prognostication effect for the hearing improvement at the fixed stage was an initial I/Clatency on affected-ear stimulation of 1.34 (between subgroups of complete and partial recovery) and an initial I/Clatency on healthy-ear stimulation of 0.76 (between subgroups of partial and no recovery), respectively. This study suggested that a dynamic process of central auditory plasticity can be induced by peripheral lesions. The hemispheric asymmetry at the initial stage bears an excellent prognostic potential for the treatment outcomes and hearing level at the fixed stage in ISSNHL. Our study demonstrated that such brain signature of central auditory plasticity in terms of both N100m latency and amplitude at defined time can serve as a prognostication predictor for ISSNHL. Further studies are needed to explore the long-term temporal scenario of auditory hemispheric asymmetry and to get better psychoacoustic correlates of pathological hemispheric asymmetry in ISSNHL. PMID:22532839

Lansoprazole use and tuberculosis incidence in the United Kingdom Clinical Practice Research Datalink: A population based cohort

PubMed Central

Yates, Tom A.; Tomlinson, Laurie A.; Bhaskaran, Krishnan; Langan, Sinead; Thomas, Sara; Smeeth, Liam

2017-01-01

Background Recent in vitro and animal studies have found the proton pump inhibitor (PPI) lansoprazole to be highly active against Mycobacterium tuberculosis. Omeprazole and pantoprazole have no activity. There is no evidence that, in clinical practice, lansoprazole can treat or prevent incident tuberculosis (TB) disease. Methods and findings We studied a cohort of new users of lansoprazole, omeprazole, or pantoprazole from the United Kingdom Clinical Practice Research Datalink to determine whether lansoprazole users have a lower incidence of TB disease than omeprazole or pantoprazole users. Negative control outcomes of myocardial infarction (MI) and herpes zoster were also studied. Multivariable Cox proportional hazards regression was used to adjust for potential confounding by a wide range of factors. We identified 527,364 lansoprazole initiators and 923,500 omeprazole or pantoprazole initiators. Lansoprazole users had a lower rate of TB disease (n = 86; 10.0 cases per 100,000 person years; 95% confidence interval 8.1–12.4) than omeprazole or pantoprazole users (n = 193; 15.3 cases per 100,000 person years; 95% confidence interval 13.3–17.7), with an adjusted hazard ratio (HR) of 0.68 (0.52–0.89). No association was found with MI (adjusted HR 1.04; 95% confidence interval 1.00–1.08) or herpes zoster (adjusted HR 1.03; 95% confidence interval 1.00–1.06). Limitations of this study are that we could not determine whether TB disease was due to reactivation of latent infection or a result of recent transmission, nor could we determine whether lansoprazole would have a beneficial effect if given to people presenting with TB disease. Conclusions In this study, use of the commonly prescribed and cheaply available PPI lansoprazole was associated with reduced incidence of TB disease. Given the serious problem of drug resistance and the adverse side effect profiles of many TB drugs, further investigation of lansoprazole as a potential antituberculosis agent is warranted. PMID:29161254

An early and late peak in microglial activation in Alzheimer's disease trajectory.

PubMed

Fan, Zhen; Brooks, David J; Okello, Aren; Edison, Paul

2017-03-01

Amyloid-β deposition, neuroinflammation and tau tangle formation all play a significant role in Alzheimer's disease. We hypothesized that there is microglial activation early on in Alzheimer's disease trajectory, where in the initial phase, microglia may be trying to repair the damage, while later on in the disease these microglia could be ineffective and produce proinflammatory cytokines leading to progressive neuronal damage. In this longitudinal study, we have evaluated the temporal profile of microglial activation and its relationship between fibrillar amyloid load at baseline and follow-up in subjects with mild cognitive impairment, and this was compared with subjects with Alzheimer's disease. Thirty subjects (eight mild cognitive impairment, eight Alzheimer's disease and 14 controls) aged between 54 and 77 years underwent 11C-(R)PK11195, 11C-PIB positron emission tomography and magnetic resonance imaging scans. Patients were followed-up after 14 ± 4 months. Region of interest and Statistical Parametric Mapping analysis were used to determine longitudinal alterations. Single subject analysis was performed to evaluate the individualized pathological changes over time. Correlations between levels of microglial activation and amyloid deposition at a voxel level were assessed using Biological Parametric Mapping. We demonstrated that both baseline and follow-up microglial activation in the mild cognitive impairment cohort compared to controls were increased by 41% and 21%, respectively. There was a longitudinal reduction of 18% in microglial activation in mild cognitive impairment cohort over 14 months, which was associated with a mild elevation in fibrillar amyloid load. Cortical clusters of microglial activation and amyloid deposition spatially overlapped in the subjects with mild cognitive impairment. Baseline microglial activation was increased by 36% in Alzheimer's disease subjects compared with controls. Longitudinally, Alzheimer's disease subjects showed an increase in microglial activation. In conclusion, this is one of the first longitudinal positron emission tomography studies evaluating longitudinal changes in microglial activation in mild cognitive impairment and Alzheimer's disease subjects. We found there is an initial longitudinal reduction in microglial activation in subjects with mild cognitive impairment, while subjects with Alzheimer's disease showed an increase in microglial activation. This could reflect that activated microglia in mild cognitive impairment initially may adopt a protective activation phenotype, which later change to a cidal pro-inflammatory phenotype as disease progresses and amyloid clearance fails. Thus, we speculate that there might be two peaks of microglial activation in the Alzheimer's disease trajectory; an early protective peak and a later pro-inflammatory peak. If so, anti-microglial agents targeting the pro-inflammatory phenotype would be most beneficial in the later stages of the disease. © The Author (2017). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

A Focused Ethnographic Study of Sri Lankan Government Field Veterinarians’ Decision Making about Diagnostic Laboratory Submissions and Perceptions of Surveillance

PubMed Central

Sawford, Kate; Vollman, Ardene Robinson; Stephen, Craig

2012-01-01

The global public health community is facing the challenge of emerging infectious diseases. Historically, the majority of these diseases have arisen from animal populations at lower latitudes where many nations experience marked resource constraints. In order to minimize the impact of future events, surveillance of animal populations will need to enable prompt event detection and response. Many surveillance systems targeting animals rely on veterinarians to submit cases to a diagnostic laboratory or input clinical case data. Therefore understanding veterinarians’ decision-making process that guides laboratory case submission and their perceptions of infectious disease surveillance is foundational to interpreting disease patterns reported by laboratories and engaging veterinarians in surveillance initiatives. A focused ethnographic study was conducted with twelve field veterinary surgeons that participated in a mobile phone-based surveillance pilot project in Sri Lanka. Each participant agreed to an individual in-depth interview that was recorded and later transcribed to enable thematic analysis of the interview content. Results found that field veterinarians in Sri Lanka infrequently submit cases to laboratories – so infrequently that common case selection principles could not be described. Field veterinarians in Sri Lanka have a diagnostic process that operates independently of laboratories. Participants indicated a willingness to take part in surveillance initiatives, though they highlighted a need for incentives that satisfy a range of motivations that vary among field veterinarians. This study has implications for the future of animal health surveillance, including interpretation of disease patterns reported, system design and implementation, and engagement of data providers. PMID:23133542

How Does Cardiovascular Disease First Present in Women and Men? Incidence of 12 Cardiovascular Diseases in a Contemporary Cohort of 1,937,360 People.

PubMed

George, Julie; Rapsomaniki, Eleni; Pujades-Rodriguez, Mar; Shah, Anoop Dinesh; Denaxas, Spiros; Herrett, Emily; Smeeth, Liam; Timmis, Adam; Hemingway, Harry

2015-10-06

Given the recent declines in heart attack and stroke incidence, it is unclear how women and men differ in first lifetime presentations of cardiovascular diseases (CVDs). We compared the incidence of 12 cardiac, cerebrovascular, and peripheral vascular diseases in women and men at different ages. We studied 1 937 360 people, aged ≥ 30 years and free from diagnosed CVD at baseline (51% women), using linked electronic health records covering primary care, hospital admissions, acute coronary syndrome registry, and mortality (Cardiovascular Research Using LInked Bespoke Studies and Electronic Records [CALIBER] research platform). During 6 years median follow-up between 1997 and 2010, 114 859 people experienced an incident cardiovascular diagnosis, the majority (66%) of which were neither myocardial infarction nor ischemic stroke. Associations of male sex with initial diagnoses of CVD, however, varied from strong (age-adjusted hazard ratios, 3.6-5.0) for abdominal aortic aneurysm, myocardial infarction, and unheralded coronary death (particularly >60 years), through modest (hazard ratio, 1.5-2.0) for stable angina, ischemic stroke, peripheral arterial disease, heart failure, and cardiac arrest, to weak (hazard ratio <1.5) for transient ischemic attack, intracerebral hemorrhage, and unstable angina, and inverse (0.69) for subarachnoid hemorrhage (all P<0.001). The majority of initial presentations of CVD are neither myocardial infarction nor ischemic stroke, yet most primary prevention studies focus on these presentations. Sex has differing associations with different CVDs, with implications for risk prediction and management strategies. URL: http://www.clinicaltrials.gov. Unique identifier: NCT01164371. © 2015 The Authors.

Chronic disease self-management education courses: utilization by low-income, middle-aged participants.

PubMed

Horrell, Lindsey N; Kneipp, Shawn M; Ahn, SangNam; Towne, Samuel D; Mingo, Chivon A; Ory, Marcia G; Smith, Matthew Lee

2017-06-27

Individuals living in lower-income areas face an increased prevalence of chronic disease and, oftentimes, greater barriers to optimal self-management. Disparities in disease management are seen across the lifespan, but are particularly notable among middle-aged adults. Although evidence-based Chronic Disease Self-management Education courses are available to enhance self-management among members of this at-risk population, little information is available to determine the extent to which these courses are reaching those at greatest risk. The purpose of this study is to compare the extent to which middle-aged adults from lower- and higher-income areas have engaged in CDSME courses, and to identify the sociodemographic characteristics of lower-income, middle aged participants. The results of this study were produced through analysis of secondary data collected during the Communities Putting Prevention to Work: Chronic Disease Self-Management Program initiative. During this initiative, data was collected from 100,000 CDSME participants across 45 states within the United States, the District of Columbia, and Puerto Rico. Of the entire sample included in this analysis (19,365 participants), 55 people lived in the most impoverished counties. While these 55 participants represented just 0.3% of the total study sample, researchers found this group completed courses more frequently than participants from less impoverished counties once enrolled. These results signal a need to enhance participation of middle-aged adults from lower-income areas in CDSME courses. The results also provide evidence that can be used to inform future program delivery choices, including decisions regarding recruitment materials, program leaders, and program delivery sites, to better engage this population.

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.

Health effects of swimming in fecally-contaminated recreational water: Results from studies at nine coastal beaches

EPA Science Inventory

Exposure to fecally-contaminated water has long been known to transmit infectious disease. In 2003, EPA and the CDC initiated studies to better describe the health effects associated with exposure to fecal contamination in recreational waters and to test faster ways of measuring ...

Movement behaviour of patients with eating disorders and inflammatory bowel disease: a controlled study.

PubMed

Lausberg, H; von Wietersheim, J; Feiereis, H

1996-01-01

This study assessed the movement behaviour of patients with eating disorders and inflammatory bowel disease. Ninety female patients with anorexia nervosa (n = 30), bulimia nervosa (n = 30), inflammatory bowel disease (n = 30) and a healthy control group (n = 30) were videotaped during a 10-min standardised movement sequence. A movement analysis instrument was developed for the evaluation. The patient groups had a significantly smaller area of movement, less weight shift, more isolated use of their body parts, less integration of the lower body, more peripheral initiation of movement, less strength. No significant differences could be found among the patient groups with eating disorders and inflammatory bowel disease. The findings are discussed in relation to body scheme disturbances and inhibition of nonverbal expression.

Leg raise increases pressure in lower and upper esophageal sphincter among patients with gastroesophageal reflux disease.

PubMed

Bitnar, P; Stovicek, J; Andel, R; Arlt, J; Arltova, M; Smejkal, M; Kolar, P; Kobesova, A

2016-07-01

The purpose of this study was to determine the relation between posturally increased intra-abdominal pressure and lower/upper esophageal sphincter pressure changes in patients with gastroesophageal reflux disease. We used high resolution manometry to measure pressure changes in lower and upper esophageal sphincter during bilateral leg rise. We also examined whether the rate of lower and upper esophageal sphincter pressure would increase during leg raise differentially in individuals with versus without normal resting pressure. Fifty eight patients with gastroesophageal reflux disease participated in the study. High resolution manometry was performed in relaxed supine position, then lower and upper esophageal sphincter pressure was measured. Finally, the subjects were instructed to keep their legs lifted while performing 90-degree flexion at the hips and knees and the pressure was measured again. Paired t-test and independent samples t-test were used. There was a significant increase in both lower (P < 0.001) and upper esophageal sphincter pressure (P = 0.034) during leg raise compared to the initial resting position. Individuals with initially higher pressure in lower esophageal sphincter (>10 mmHg) exhibited a greater pressure increase during leg raise than those with initially lower pressure (pressure ≤10 mmHg; P = 0.002). Similarly individuals with higher resting upper esophageal sphincter pressure (>44 mmHg) showed a greater pressure increase during leg raise than those with lower resting pressure (≤44 mmHg; P < 0.001). The results illustrate the influence of postural leg activities on intraesophageal pressure in patients with gastroesophageal reflux disease, indicating by means of high resolution manometry that diaphragmatic postural and sphincter function are likely interrelated in this population. Copyright © 2015 Elsevier Ltd. All rights reserved.

Initial direct comparison of 99mTc-TOC and 99mTc-TATE in identifying sites of disease in patients with proven GEP NETs.

PubMed

Cwikla, Jaroslaw B; Mikolajczak, Renata; Pawlak, Dariusz; Buscombe, John R; Nasierowska-Guttmejer, Anna; Bator, Andrzej; Maecke, Helmut R; Walecki, Jerzy

2008-07-01

The imaging of neuroendocrine tumors has become one of the most significant areas in nuclear oncology. In an attempt to provide high-quality imaging and possible sensitivity at a reduced cost, time, and radiation dose, several (99m)Tc agents have been proposed. The aim of this initial study was to compare the tumor uptake and biodistribution of 2 new 6-hydrazinopyridine-3-carboxylic acid (HYNIC)-derivatized Tyr(3)-octreotide analogs, (99m)Tc-[HYNIC,Tyr(3)]octreotide ((99m)Tc-TOC) and (99m)Tc-[HYNIC,Tyr(3),Thr(8)]octreotide ((99m)Tc-TATE), in patients with somatostatin receptor-expressing tumors. Each of 12 patients with proven gastrointestinal pancreatic neuroendocrine tumors received a mean activity of 520 MBq of (99m)Tc-TOC and (99m)Tc-TATE. Scintigraphy with both tracers was performed 3-4 h after their injection using standard whole-body and SPECT imaging. The images were reviewed subjectively by 2 readers, who reported tumor uptake lesion by lesion. Both radiotracers demonstrated concordance between the results in 7 patients (58%). In total, 110 sites of disease were identified with (99m)Tc-TOC, compared with 115 with (99m)Tc-TATE. There was 1 case in which (99m)Tc-TOC identified sites of disease not seen on (99m)Tc-TATE imaging but 4 cases in which some sites of disease were seen with (99m)Tc-TATE and not (99m)Tc-TOC. In this initial study, both tracers seem to show similar sites of tumor, with (99m)Tc-TATE having a slight edge in the total number of lesions seen, especially in lymph node metastases.

Functional and morphological assessment of ocular structures and follow-up of patients with early-stage Parkinson's disease.

PubMed

Hasanov, Samir; Demirkilinc Biler, Elif; Acarer, Ahmet; Akkın, Cezmi; Colakoglu, Zafer; Uretmen, Onder

2018-05-09

To evaluate and follow-up of functional and morphological changes of the optic nerve and ocular structures prospectively in patients with early-stage Parkinson's disease. Nineteen patients with a diagnosis of early-stage Parkinson's disease and 19 age-matched healthy controls were included in the study. All participants were examined minimum three times at the intervals of at least 6 month following initial examination. Pattern visually evoked potentials (VEP), contrast sensitivity assessments at photopic conditions, color vision tests with Ishihara cards and full-field visual field tests were performed in addition to measurement of retinal nerve fiber layer (RNFL) thickness of four quadrants (top, bottom, nasal, temporal), central and mean macular thickness and macular volumes. Best corrected visual acuity was observed significantly lower in study group within all three examinations. Contrast sensitivity values of the patient group were significantly lower in all spatial frequencies. P100 wave latency of VEP was significantly longer, and amplitude was lower in patient group; however, significant deterioration was not observed during the follow-up. Although average peripapillary RNFL thickness was not significant between groups, RNFL thickness in the upper quadrant was thinner in the patient group. While there was no difference in terms of mean macular thickness and total macular volume values between the groups initially, a significant decrease occurred in the patient group during the follow-up. During the initial and follow-up process, a significant deterioration in visual field was observed in the patient group. Structural and functional disorders shown as electro-physiologically and morphologically exist in different parts of visual pathways in early-stage Parkinson's disease.

Is there an association between suicide attempt and delay of initiation of mood stabilizers in bipolar I disorder?

PubMed

Nery-Fernandes, Fabiana; Quarantini, Lucas C; Guimarães, José L; de Oliveira, Irismar R; Koenen, Karestan C; Kapczinski, Flavio; Miranda-Scippa, Ângela

2012-02-01

Little is known about the extent to which delay of initiation of mood-stabilizing treatment may influence outcomes in bipolar patients (BP). In this study, our aim was to investigate the association between delay of mood stabilizer treatment in bipolar patients and lifetime history of suicide attempts. A consecutive sample of 268 bipolar I outpatients from two teaching hospitals in Brazil was recruited. The assessment included a socio-demographic history form, a clinical interview regarding clinical variables and the Structured Clinical Interview for DSM-IV. Participants were divided into three groups: BP that initiated the first mood stabilizer in the same year of the first episode of the disease (FMS≤1), between 1 and 5 years after the first episode of the disease (15). The mean time from the first episode until the first mood stabilizer medication was 8.6 years (SD 9.8 years). The FMS>5 group, showed a higher lifetime prevalence of suicide attempts than the other two groups (PR=1.75, 95% CI: 1.24-2.47), p=0.001. These results remained significant after adjusting for potential confounders, (PR=1.82, 95% CI: 1.29-2.60), p=0.001. This study evaluated patients retrospectively and does not permit a cause-effect relationship. The present study supports the importance of early diagnosis and early intervention for BP in order to limit the potentially lethal impact of the disease. Copyright © 2011 Elsevier B.V. All rights reserved.

Impact of Targeted Programs on Health Systems: A Case Study of the Polio Eradication Initiative

PubMed Central

Loevinsohn, Benjamin; Aylward, Bruce; Steinglass, Robert; Ogden, Ellyn; Goodman, Tracey; Melgaard, Bjorn

2002-01-01

The results of 2 large field studies on the impact of the polio eradication initiative on health systems and 3 supplementary reports were presented at a December 1999 meeting convened by the World Health Organization. All of these studies concluded that positive synergies exist between polio eradication and health systems but that these synergies have not been vigorously exploited. The eradication of polio has probably improved health systems worldwide by broadening distribution of vitamin A supplements, improving cooperation among enterovirus laboratories, and facilitating linkages between health workers and their communities. The results of these studies also show that eliminating polio did not cause a diminution of funding for immunization against other illnesses. Relatively little is known about the opportunity costs of polio eradication. Improved planning in disease eradication initiatives can minimize disruptions in the delivery of other services. Future initiatives should include indicators and baseline data for monitoring effects on health systems development. PMID:11772750

Diagnosis of Parkinson’s disease on the basis of clinical–genetic classification: a population-based modelling study

PubMed Central

Nalls, Mike A.; McLean, Cory Y.; Rick, Jacqueline; Eberly, Shirley; Hutten, Samantha J.; Gwinn, Katrina; Sutherland, Margaret; Martinez, Maria; Heutink, Peter; Williams, Nigel; Hardy, John; Gasser, Thomas; Brice, Alexis; Price, T. Ryan; Nicolas, Aude; Keller, Margaux F.; Molony, Cliona; Gibbs, J. Raphael; Chen-Plotkin, Alice; Suh, Eunran; Letson, Christopher; Fiandaca, Massimo S.; Mapstone, Mark; Federoff, Howard J.; Noyce, Alastair J; Morris, Huw; Van Deerlin, Vivianna M.; Weintraub, Daniel; Zabetian, Cyrus; Hernandez, Dena G.; Lesage, Suzanne; Mullins, Meghan; Conley, Emily Drabant; Northover, Carrie; Frasier, Mark; Marek, Ken; Day-Williams, Aaron G.; Stone, David J.; Ioannidis, John P. A.; Singleton, Andrew B.

2015-01-01

Background Accurate diagnosis and early detection of complex disease has the potential to be of enormous benefit to clinical trialists, patients, and researchers alike. We sought to create a non-invasive, low-cost, and accurate classification model for diagnosing Parkinson’s disease risk to serve as a basis for future disease prediction studies in prospective longitudinal cohorts. Methods We developed a simple disease classifying model within 367 patients with Parkinson’s disease and phenotypically typical imaging data and 165 controls without neurological disease of the Parkinson’s Progression Marker Initiative (PPMI) study. Olfactory function, genetic risk, family history of PD, age and gender were algorithmically selected as significant contributors to our classifying model. This model was developed using the PPMI study then tested in 825 patients with Parkinson’s disease and 261 controls from five independent studies with varying recruitment strategies and designs including the Parkinson’s Disease Biomarkers Program (PDBP), Parkinson’s Associated Risk Study (PARS), 23andMe, Longitudinal and Biomarker Study in PD (LABS-PD), and Morris K. Udall Parkinson’s Disease Research Center of Excellence (Penn-Udall). Findings Our initial model correctly distinguished patients with Parkinson’s disease from controls at an area under the curve (AUC) of 0.923 (95% CI = 0.900 – 0.946) with high sensitivity (0.834, 95% CI = 0.711 – 0.883) and specificity (0.903, 95% CI = 0.824 – 0.946) in PPMI at its optimal AUC threshold (0.655). The model is also well-calibrated with all Hosmer-Lemeshow simulations suggesting that when parsed into random subgroups, the actual data mirrors that of the larger expected data, demonstrating that our model is robust and fits well. Likewise external validation shows excellent classification of PD with AUCs of 0.894 in PDBP, 0.998 in PARS, 0.955 in 23andMe, 0.929 in LABS-PD, and 0.939 in Penn-Udall. Additionally, when our model classifies SWEDD as PD, they convert within one year to typical PD more than would be expected by chance, with 4 out of 17 classified as PD converting to PD during brief follow-up; while SWEDD not classified as PD showed one conversion to PD out of 38 participants (test of proportions, p-value = 0.003). Interpretation This model may serve as a basis for future investigations into the classification, prediction and treatment of Parkinson’s disease, particularly those planning on attempting to identify prodromal or preclinical etiologically typical PD cases in prospective cohorts for efficient interventional and biomarker studies. Funding Please see the acknowledgements and funding section at the end of the manuscript. PMID:26271532

Education and dementia in the context of the cognitive reserve hypothesis: a systematic review with meta-analyses and qualitative analyses.

PubMed

Meng, Xiangfei; D'Arcy, Carl

2012-01-01

Cognitive reserve (CR) or brain reserve capacity explains why individuals with higher IQ, education, or occupational attainment have lower risks of developing dementia, Alzheimer's disease (AD) or vascular dementia (VaD). The CR hypothesis postulates that CR reduces the prevalence and incidence of AD or VaD. It also hypothesizes that among those who have greater initial cognitive reserve (in contrast to those with less reserve) greater brain pathology occurs before the clinical symptoms of disease becomes manifest. Thus clinical disease onset triggers a faster decline in cognition and function, and increased mortality among those with initial greater cognitive reserve. Disease progression follows distinctly separate pathological and clinical paths. With education as a proxy we use meta-analyses and qualitative analyses to review the evidence for the CR hypothesis. We searched PubMed, PsycoINFO, EMBASE, HealthStar, and Scopus databases from January 1980 to June 2011 for observational studies with clear criteria for dementia, AD or VaD and education. One hundred and thirty-three articles with a variety of study designs met the inclusion criteria. Prevalence and incidence studies with odds ratios (ORs), relative risks or original data were included in the meta-analyses. Other studies were reviewed qualitatively. The studies covered 437,477 subjects. Prevalence and incidence studies with pooled ORs of 2.61 (95%CI 2.21-3.07) and 1.88 (95%CI 1.51-2.34) respectively, showed low education increased the risk of dementia. Heterogeneity and sensitivity tests confirmed the evidence. Generally, study characteristics had no effect on conclusions. Qualitative analyses also showed the protective effects of higher education on developing dementia and with clinical disease onset hastening a decline in cognition and function, and greater brain pathology. This systematic review and meta-analyses covering a wide range of observational studies and diverse settings provides robust support for the CR hypothesis. The CR hypothesis suggests several avenues for dementia prevention.

Implementation of a study to examine the persistence of Ebola virus in the body fluids of Ebola virus disease survivors in Sierra Leone: Methodology and lessons learned

PubMed Central

Marrinan, Jaclyn E.; Sesay, Foday R.; Ervin, Elizabeth; Thorson, Anna E.; Xu, Wenbo; Ströher, Ute; Ongpin, Patricia; Abad, Neetu; Ariyarajah, Archchun; Malik, Tasneem; Liu, Hongtu; Ross, Christine; Durski, Kara N.; Gaillard, Philippe; Morgan, Oliver; Formenty, Pierre; Knust, Barbara; Broutet, Nathalie; Sahr, Foday

2017-01-01

Background The 2013–2016 West African Ebola virus disease epidemic was unprecedented in terms of the number of cases and survivors. Prior to this epidemic there was limited data available on the persistence of Ebola virus in survivors’ body fluids and the potential risk of transmission, including sexual transmission. Methodology/Principal findings Given the urgent need to determine the persistence of Ebola virus in survivors’ body fluids, an observational cohort study was designed and implemented during the epidemic response operation in Sierra Leone. This publication describes study implementation methodology and the key lessons learned. Challenges encountered during implementation included unforeseen duration of follow-up, complexity of interpreting and communicating laboratory results to survivors, and the urgency of translating research findings into public health practice. Strong community engagement helped rapidly implement the study during the epidemic. The study was conducted in two phases. The first phase was initiated within five months of initial protocol discussions and assessed persistence of Ebola virus in semen of 100 adult men. The second phase assessed the persistence of virus in multiple body fluids (semen or vaginal fluid, menstrual blood, breast milk, and urine, rectal fluid, sweat, saliva, tears), of 120 men and 120 women. Conclusion/Significance Data from this study informed national and global guidelines in real time and demonstrated the need to implement semen testing programs among Ebola virus disease survivors. The lessons learned and study tools developed accelerated the implementation of such programs in Ebola virus disease affected countries, and also informed studies examining persistence of Zika virus. Research is a vital component of the public health response to an epidemic of a poorly characterized disease. Adequate resources should be rapidly made available to answer critical research questions, in order to better inform response efforts. PMID:28892501

Implementation of a study to examine the persistence of Ebola virus in the body fluids of Ebola virus disease survivors in Sierra Leone: Methodology and lessons learned.

PubMed

Deen, Gibrilla Fadlu; McDonald, Suzanna L R; Marrinan, Jaclyn E; Sesay, Foday R; Ervin, Elizabeth; Thorson, Anna E; Xu, Wenbo; Ströher, Ute; Ongpin, Patricia; Abad, Neetu; Ariyarajah, Archchun; Malik, Tasneem; Liu, Hongtu; Ross, Christine; Durski, Kara N; Gaillard, Philippe; Morgan, Oliver; Formenty, Pierre; Knust, Barbara; Broutet, Nathalie; Sahr, Foday

2017-09-01

The 2013-2016 West African Ebola virus disease epidemic was unprecedented in terms of the number of cases and survivors. Prior to this epidemic there was limited data available on the persistence of Ebola virus in survivors' body fluids and the potential risk of transmission, including sexual transmission. Given the urgent need to determine the persistence of Ebola virus in survivors' body fluids, an observational cohort study was designed and implemented during the epidemic response operation in Sierra Leone. This publication describes study implementation methodology and the key lessons learned. Challenges encountered during implementation included unforeseen duration of follow-up, complexity of interpreting and communicating laboratory results to survivors, and the urgency of translating research findings into public health practice. Strong community engagement helped rapidly implement the study during the epidemic. The study was conducted in two phases. The first phase was initiated within five months of initial protocol discussions and assessed persistence of Ebola virus in semen of 100 adult men. The second phase assessed the persistence of virus in multiple body fluids (semen or vaginal fluid, menstrual blood, breast milk, and urine, rectal fluid, sweat, saliva, tears), of 120 men and 120 women. Data from this study informed national and global guidelines in real time and demonstrated the need to implement semen testing programs among Ebola virus disease survivors. The lessons learned and study tools developed accelerated the implementation of such programs in Ebola virus disease affected countries, and also informed studies examining persistence of Zika virus. Research is a vital component of the public health response to an epidemic of a poorly characterized disease. Adequate resources should be rapidly made available to answer critical research questions, in order to better inform response efforts.

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

A workplace breast cancer screening program. Costs and components.

PubMed

Schrammel, P; Griffiths, R I; Griffiths, C B

1998-11-01

Screening for breast cancer can result in early detection of malignancies and lives saved. Many employers now offer periodic screening as an employee health benefit, and some have established screening programs in the workplace. This study was performed to identify the employer costs of breast cancer screening in the workplace, referrals for suspicious findings, and initial treatment of malignant disease. Additionally, the costs for these same services, had they been obtained outside of a workplace screening program, were estimated. Data on program components and associated costs for an established employer based breast cancer screening program were obtained. These costs were compared to those among a hypothetical cohort of women not enrolled in the workplace screening program. From 1989 through 1995, 1,416 women participated in the program. Nearly 2,500 screening mammograms and approximately 2,773 clinical breast examinations were performed, resulting in 292 referrals to physicians outside of the program for additional diagnostic procedures and treatment as needed. These referrals resulted in the detection of 12 malignancies: 8 Stage I; 3 Stage II; and 1 Stage III. Mammographic and clinical breast examination screening cost $249,041; referrals resulting in benign disease or no detectable disease cost $185,002; and referrals resulting in malignant disease, followed by initial treatment, cost $148,530. Therefore, the total cost was $582,573. Approximately 47% of the cost of referrals and initial treatment were due to employee lost productivity. Total cost in the hypothetical cohort was $1,067,948 under the assumptions that all women received screening outside of the workplace, and that the same number of malignancies were detected at the same stage as in the workplace program. These findings indicate referrals resulting in detection of benign disease or no disease accounted for a substantial proportion of the total cost of the program. In addition, employee lost productivity accounted for almost 50% of the cost of all referrals and initial treatment. Workplace screening is a relatively efficient approach for early detection of breast cancer when compared to off site screening or no screening. The efficiency could be improved with a reduction in the number and cost of unnecessary referrals.

Australian Community Pharmacists' Experience of Implementing a Chronic Kidney Disease Risk Assessment Service.

PubMed

Gheewala, Pankti A; Peterson, Gregory M; Zaidi, Syed Tabish R; Jose, Matthew D; Castelino, Ronald L

2018-06-14

Community pharmacists are well positioned to deliver chronic kidney disease (CKD) screening services. However, little is known about the challenges faced by pharmacists during service implementation. This study aimed to explore community pharmacists' experiences and perceived barriers of implementing a CKD risk assessment service. Data collection was performed by using semistructured, open-ended interview questions. Pharmacists who had implemented a CKD screening service in Tasmania, Australia, were eligible to participate. A purposeful sampling strategy was used to select pharmacists, with variation in demographics and pharmacy location. A conventional content analysis approach was used to conduct the qualitative study. Transcripts were thematically analyzed by using the NVivo 11 software program. Initially, a list of free nodes was generated and data were coded exhaustively into relevant nodes. These nodes were then regrouped to form highly conceptualized themes. Five broad themes emerged from the analysis: contextual fit within community pharmacy; perceived scope of pharmacy practice; customer perception toward disease prevention; CKD - an underestimated disease; and remuneration for a beneficial service. Pharmacists found the CKD service efficient, user-friendly, and of substantial benefit to their customers. However, several pharmacists observed that their customers lacked interest in disease prevention, and had limited understanding of CKD. More importantly, pharmacists perceived the scope of pharmacy practice to depend substantially on interprofessional collaboration between pharmacists and general practitioners, and customer acknowledgment of pharmacists' role in disease prevention. Community pharmacists perceived the CKD service to be worth incorporating into pharmacy practice. To increase uptake, future CKD services should aim to improve customer awareness about CKD before providing risk assessment. Further research investigating strategies to enhance general practitioner involvement in pharmacist-initiated disease prevention services is also needed.

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

PubMed

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

2014-09-01

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

The enduring importance of animal modelsin understanding periodontal disease

PubMed Central

Hajishengallis, George; Lamont, Richard J; Graves, Dana T

2015-01-01

Whereas no single animal model can reproduce the complexity of periodontitis, different aspects of the disease can be addressed by distinct models. Despite their limitations, animal models are essential for testing the biological significance of in vitro findings and for establishing cause-and-effect relationships relevant to clinical observations, which are typically correlative. We provide evidence that animal-based studies have generated a durable framework for dissecting the mechanistic basis of periodontitis. These studies have solidified the etiologic role of bacteria in initiating the inflammatory response that leads to periodontal bone loss and have identified key mediators (IL-1, TNF, prostaglandins, complement, RANKL) that induce inflammatory breakdown. Moreover, animal studies suggest that dysbiosis, rather than individual bacterial species, are important in initiating periodontal bone loss and have introduced the concept that organisms previously considered commensals can play important roles as accessory pathogens or pathobionts. These studies have also provided insight as to how systemic conditions, such as diabetes or leukocyte adhesion deficiency, contribute to tissue destruction. In addition, animal studies have identified and been useful in testing therapeutic targets. PMID:25574929

Requirements for pharmacokinetic evaluation of antibiotics in phase I studies.

PubMed

Bergan, T

1986-01-01

Initial pharmacokinetic studies usually include healthy volunteers to minimize variation generated by diseases. Ethical aspects of initial studies are paramount. The guidelines of the Helsinki Declaration should be followed or even extended. Thorough toxicologic screening in animals is a prerequisite. The use of radioisotopes for pharmacokinetic studies should be limited. The basic design of studies includes cross-over administration of intravenous and oral doses of several sizes. Bioavailability, total area under the serum concentration curve, serum half-life, amount eliminated in urine as active drug, and metabolism are the most important data. The fate of the parent compound and of its possible metabolites in both healthy persons and ill individuals (including those with renal or hepatic dysfunction) should be monitored. Diet may have consequences with regard to recommended dosage schedules. When possible, tissue penetration of antibiotics should be assessed, preferably through the analysis of peripheral human lymph and of suction-blister and peritoneal fluids. Theoretical dosage schedules based on pharmacokinetic assessments in healthy persons should be tested in patients with infectious disease, particularly in those with reduced renal and/or hepatic function.

Crosstalk between the Unfolded Protein Response and NF-κB-Mediated Inflammation in the Progression of Chronic Kidney Disease

PubMed Central

Cruz, Gaile L.; Dickhout, Jeffrey G.

2015-01-01

The chronic inflammatory response is emerging as an important therapeutic target in progressive chronic kidney disease. A key transcription factor in the induction of chronic inflammation is NF-κB. Recent studies have demonstrated that sustained activation of the unfolded protein response (UPR) can initiate this NF-κB signaling phenomenon and thereby induce chronic kidney disease progression. A key factor influencing chronic kidney disease progression is proteinuria and this condition has now been demonstrated to induce sustained UPR activation. This review details the crosstalk between the UPR and NF-κB pathways as pertinent to chronic kidney disease. We present potential tools to study this phenomenon as well as potential therapeutics that are emerging to regulate the UPR. These therapeutics may prevent inflammation specifically induced in the kidney due to proteinuria-induced sustained UPR activation. PMID:25977931

A Comprehensive Fluid Dynamic-Diffusion Model of Blood Microcirculation with Focus on Sickle Cell Disease

NASA Astrophysics Data System (ADS)

Le Floch, Francois; Harris, Wesley L.

2009-11-01

A novel methodology has been developed to address sickle cell disease, based on highly descriptive mathematical models for blood flow in the capillaries. Our investigations focus on the coupling between oxygen delivery and red blood cell dynamics, which is crucial to understanding sickle cell crises and is unique to this blood disease. The main part of our work is an extensive study of blood dynamics through simulations of red cells deforming within the capillary vessels, and relies on the use of a large mathematical system of equations describing oxygen transfer, blood plasma dynamics and red cell membrane mechanics. This model is expected to lead to the development of new research strategies for sickle cell disease. Our simulation model could be used not only to assess current researched remedies, but also to spur innovative research initiatives, based on our study of the physical properties coupled in sickle cell disease.

Blood pressure and risk of all-cause mortality in advanced chronic kidney disease and hemodialysis: the CRIC study

PubMed Central

Bansal, Nisha; McCulloch, Charles E.; Rahman, Mahboob; Kusek, John W.; Anderson, Amanda H.; Xie, Dawei; Townsend, Raymond R.; Lora, Claudia M.; Wright, Jackson; Go, Alan S.; Ojo, Akinlolu; Alper, Arnold; Lustigova, Eva; Cuevas, Magda; Kallem, Radhakrishna; Hsu, Chi-yuan

2014-01-01

Studies of hemodialysis patients have shown a U-shaped association between systolic blood pressure (SBP) and mortality. These studies have largely relied on dialysis-unit SBP measures and have not evaluated whether this U-shape also exists in advanced chronic kidney disease (CKD), prior to starting hemodialysis. We determined the association between SBP and mortality at advanced CKD and again after initiation of hemodialysis. This was a prospective study of Chronic Renal Insufficiency Cohort (CRIC) participants with advanced CKD followed through initiation of hemodialysis. We studied the association between SBP and mortality when participants: 1) had an estimated glomerular filtration rate <30 ml/min/1.73m2 (N=1,705); 2) initiated hemodialysis and had dialysis-unit SBP measures (N=403) and; 3) initiated hemodialysis and had out-of-dialysis-unit SBP measured at a CRIC study visit (N=326). Cox models adjusted for demographics, cardiovascular risk factors and dialysis parameters. A quadratic term for SBP was included to test for a U-shaped association. At advanced CKD, there was no association between SBP and mortality (HR 1.02 [95% CI: 0.98–1.07] per every 10 mm Hg increase). Among participants who started hemodialysis, a U-shaped association between dialysis-unit SBP and mortality was observed. In contrast, there was a linear association between out-of-dialysis-unit SBP and mortality (HR 1.26 [95% CI: 1.14–1.40] per every 10 mm Hg increase). In conclusion, more efforts should be made to obtain out-of-dialysis-unit SBP which may merit more consideration as a target for clinical management and in interventional trials. PMID:25287404

Effect of Promotional Initiatives on Visits to a Dedicated Website for Physical Activity and Non-Communicable Disease in Luxembourg: An Event Study

PubMed Central

Lion, Alexis; Thornton, Jane S.; Vaillant, Michel; Pertuy, Juliette; Besenius, Eric; Hardy, Cyrille; Delagardelle, Charles; Seil, Romain; Urhausen, Axel; Theisen, Daniel

2017-01-01

The Sport-Santé project and its website (www.sport-sante.lu) promote physical activity for individuals with non-communicable diseases (NCDs) in Luxembourg. Our purpose was to perform an event study analysis to evaluate the effects of communication and promotional initiatives on the number of visits to the Sport-Santé website. Between September 2015 and May 2016, the Sport-Santé website was promoted during different initiatives, including participation in health-related events or publication of articles in local journals. The daily number of visits to www.sport-sante.lu website (i.e., our outcome) was recorded using Google Analytics and compared to a counterfactual collected with its benchmarking tool. The counterfactual was defined as the daily number of visits to websites in the same field. A model was created to evaluate the relationship between the number of visits to www.sport-sante.lu website and the number of visits to similar websites during a control period with no promotional initiatives (from July 2015 to September 2015). The effect of promotional initiatives was subsequently tested, by comparing the actual number of visits to our website (up to 2 days after each event) with the theoretical number of visits predicted by the model. Twenty-two initiatives were identified, of which 11 were participations at major health-related events and 11 publications of popular science articles. Of these 22 initiatives, the event study identified 2 popular science articles and 1 interactive workshop that significantly increased the daily number of visits to the www.sport-sante.lu website. One of the two articles was published on the day before the workshop was held, which did not allow us to distinguish its specific impact. The second article was published in the main national newspaper. This is the first time to our knowledge that an event study analysis has been used to evaluate the impact of promotional initiatives on the number of visits to a dedicated website for physical activity and NCDs. Our results indicate that some initiatives can aid in the number of visits, but in general their impact is limited. To observe an increased rate of participation in physical activity, additional promotional and evaluative strategies should be explored. PMID:28611975

White matter hyperintensities and cerebral amyloidosis: necessary and sufficient for clinical expression of Alzheimer disease?

PubMed

Provenzano, Frank A; Muraskin, Jordan; Tosto, Giuseppe; Narkhede, Atul; Wasserman, Ben T; Griffith, Erica Y; Guzman, Vanessa A; Meier, Irene B; Zimmerman, Molly E; Brickman, Adam M

2013-04-01

Current hypothetical models emphasize the importance of β-amyloid in Alzheimer disease (AD) pathogenesis, although amyloid alone is not sufficient to account for the dementia syndrome. The impact of small-vessel cerebrovascular disease, visualized as white matter hyperintensities (WMHs) on magnetic resonance imaging scans, may be a key factor that contributes independently to AD presentation. To determine the impact of WMHs and Pittsburgh Compound B (PIB) positron-emission tomography-derived amyloid positivity on the clinical expression of AD. Baseline PIB-positron-emission tomography values were downloaded from the Alzheimer's Disease Neuroimaging Initiative database. Total WMH volume was derived on accompanying structural magnetic resonance imaging data. We examined whether PIB positivity and total WMHs predicted diagnostic classification of patients with AD (n = 20) and control subjects (n = 21). A second analysis determined whether WMHs discriminated between those with and without the clinical diagnosis of AD among those who were classified as PIB positive (n = 28). A third analysis examined whether WMHs, in addition to PIB status, could be used to predict future risk for AD among subjects with mild cognitive impairment (n = 59). The Alzheimer's Disease Neuroimaging Initiative public database. The study involved data from 21 normal control subjects, 59 subjects with mild cognitive impairment, and 20 participants with clinically defined AD from the Alzheimer Disease's Neuroimaging Initiative database. Clinical AD diagnosis and WMH volume. Pittsburgh Compound B positivity and increased total WMH volume independently predicted AD diagnosis. Among PIB-positive subjects, those diagnosed as having AD had greater WMH volume than normal control subjects. Among subjects with mild cognitive impairment, both WMH and PIB status at baseline conferred risk for future diagnosis of AD. White matter hyperintensities contribute to the presentation of AD and, in the context of significant amyloid deposition, may provide a second hit necessary for the clinical manifestation of the disease. As risk factors for the development of WMHs are modifiable, these findings suggest intervention and prevention strategies for the clinical syndrome of AD.

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.

Korean guidelines for the diagnosis and management of dry eye: development and validation of clinical efficacy.

PubMed

Hyon, Joon Young; Kim, Hyo-Myung; Lee, Doh; Chung, Eui-Sang; Song, Jong-Suk; Choi, Chul Young; Lee, Jungbok

2014-06-01

To evaluate the clinical efficacy of newly developed guidelines for the diagnosis and management of dry eye. This retrospective, multi-center, non-randomized, observational study included a total of 1,612 patients with dry eye disease who initially visited the clinics from March 2010 to August 2010. Korean guidelines for the diagnosis and management of dry eye were newly developed from concise, expert-consensus recommendations. Severity levels at initial and final visits were determined using the guidelines in patients with 90 ± 7 days of follow-up visits (n = 526). Groups with different clinical outcomes were compared with respect to clinical parameters, treatment modalities, and guideline compliance. Main outcome measures were ocular and visual symptoms, ocular surface disease index, global assessment by patient and physician, tear film break-up time, Schirmer-1 test score, ocular surface staining score at initial and final visits, clinical outcome after three months of treatment, and guideline compliance. Severity level was reduced in 47.37% of patients treated as recommended by the guidelines. Younger age (odd ratio [OR], 0.984; p = 0.044), higher severity level at initial visit, compliance to treatment recommendation (OR, 1.832; p = 0.047), and use of topical cyclosporine (OR, 1.838; p = 0.011) were significantly associated with improved clinical outcomes. Korean guidelines for the diagnosis and management of dry eye can be used as a valid and effective tool for the treatment of dry eye disease.

Ultrasonographic imaging of inflammatory bowel disease in pediatric patients

PubMed Central

Chiorean, Liliana; Schreiber-Dietrich, Dagmar; Braden, Barbara; Cui, Xin-Wu; Buchhorn, Reiner; Chang, Jian-Min; Dietrich, Christoph F

2015-01-01

Inflammatory bowel disease (IBD) is one of the most common chronic gastrointestinal diseases in pediatric patients. Choosing the optimal imaging modality for the assessment of gastrointestinal disease in pediatric patients can be challenging. The invasiveness and patient acceptance, the radiation exposure and the quality performance of the diagnostic test need to be considered. By reviewing the literature regarding imaging in inflammatory bowel disease the value of ultrasound in the clinical management of pediatric patients is highlighted. Transabdominal ultrasound is a useful, noninvasive method for the initial diagnosis of IBD in children; it also provides guidance for therapeutic decisions and helps to characterize and predict the course of the disease in individual patients. Ultrasound techniques including color Doppler imaging and contrast-enhanced ultrasound are promising imaging tools to determine disease activity and complications. Comparative studies between different imaging methods are needed. PMID:25954096

Quality of life in newly diagnosed glaucoma patients : The Collaborative Initial Glaucoma Treatment Study.

PubMed

Janz, N K; Wren, P A; Lichter, P R; Musch, D C; Gillespie, B W; Guire, K E

2001-05-01

The Collaborative Initial Glaucoma Treatment Study (CIGTS) was designed to determine whether patients with newly diagnosed open-angle glaucoma are better treated initially by medicine or immediate filtering surgery. This paper describes the quality-of-life (QOL) measurement approach, instruments included, and the CIGTS participants' QOL findings at the time of diagnosis. Baseline results from a randomized, controlled clinical trial. Six hundred seven patients from 14 clinical centers were enrolled. Patients randomized to initial medication received a stepped medical regimen (n = 307). Those randomized to initial surgery underwent a trabeculectomy (n = 300). The baseline interview was conducted before treatment initiation. All baseline and posttreatment QOL assessments were conducted by telephone from a centralized interviewing center. The primary outcome measure described in this paper was QOL. The QOL instrument is multidimensional and incorporates both disease-specific and generic measures, including the Visual Activities Questionnaire, Sickness Impact Profile, and a Symptom and Health Problem CHECKLIST: The correlations between QOL measures and clinical outcomes were in the expected direction, but relatively weak. At initial diagnosis, difficulty with bright lights and with light and dark adaptation were the most frequently reported symptoms related to visual function, whereas visual distortion was the most bothersome. Approximately half of the patients reported at least some worry or concern about the possibility of blindness. Within the Visual Activities Questionnaire, higher scores on the Peripheral Vision subscale were associated with more field loss (P < 0.01). In regression analyses controlling for sociodemographics and nonocular comorbidities, increased visual field loss was significantly associated with higher dysfunction among five disease-specific QOL measures (P < 0.05). Newly diagnosed glaucoma patients reported experiencing some visual function symptoms at the time of diagnosis that would not be intuitively expected based on clinical testing. Some discussion about the association between clinical presentation and worry about blindness may reduce unnecessary concern. These results provide the basis for long-term comparisons of the QOL effects of initial medical and surgical treatment for open-angle glaucoma.

Epidemiology and outcomes of hypoglycemia in patients with advanced diabetic kidney disease on dialysis: A national cohort study

PubMed Central

Wang, Jhi-Joung; Weng, Shih-Feng; Lin, Chih-Ching; Chien, Chih-Chiang

2017-01-01

Background Patients with advanced diabetic kidney disease (DKD) behave differently to diabetic patients without kidney disease. We aimed to investigate the associations of hypoglycemia and outcomes after initiation of dialysis in patients with advanced DKD on dialysis. Methods Using National Health Insurance Research Database, 20,845 advanced DKD patients beginning long-term dialysis between 2002 and 2006 were enrolled. We investigated the incidence of severe hypoglycemia episodes before initiation of dialysis. Patients were followed from date of first dialysis to death, end of dialysis, or 2008. Main outcomes measured were all-cause mortality, myocardial infarction (MI), and subsequent severe hypoglycemic episodes after dialysis. Results 19.18% patients had at least one hypoglycemia episode during 1-year period before initiation of dialysis. Advanced DKD patients with higher adapted Diabetes Complications Severity Index (aDCSI) scores were associated with more frequent hypoglycemia (P for trend < 0.001). Mortality and subsequent severe hypoglycemia after dialysis both increased with number of hypoglycemic episodes. Compared to those who had no hypoglycemic episodes, those who had one had a 15% higher risk of death and a 2.3-fold higher risk of subsequent severe hypoglycemia. Those with two or more episodes had a 19% higher risk of death and a 3.9-fold higher risk of subsequent severe hypoglycemia. However, previous severe hypoglycemia was not correlated with risk of MI after dialysis. Conclusions The rate of severe hypoglycemia was high in advanced DKD patients. Patients with higher aDCSI scores tended to have more hypoglycemic episodes. Hypoglycemic episodes were associated with subsequent hypoglycemia and mortality after initiation of dialysis. We studied the associations and further study is needed to establish cause. In addition, more attention is needed for hypoglycemia prevention in advanced DKD patients, especially for those at risk patients. PMID:28355264

Altered gut transcriptome in spondyloarthropathy

PubMed Central

Laukens, D; Peeters, H; Cruyssen, B V; Boonefaes, T; Elewaut, D; De Keyser, F; Mielants, H; Cuvelier, C; Veys, E M; Knecht, K; Van Hummelen, P; Remaut, E; Steidler, L; De Vos, M; Rottiers, P

2006-01-01

Background Intestinal inflammation is a common feature of spondyloarthropathy (SpA) and Crohn's disease. Inflammation is manifested clinically in Crohn's disease and subclinically in SpA. However, a fraction of patients with SpA develops overt Crohn's disease. Aims To investigate whether subclinical gut lesions in patients with SpA are associated with transcriptome changes comparable to those seen in Crohn's disease and to examine global gene expression in non‐inflamed colon biopsy specimens and screen patients for differentially expressed genes. Methods Macroarray analysis was used as an initial genomewide screen for selecting a comprehensive set of genes relevant to Crohn's disease and SpA. This led to the identification of 2625 expressed sequence tags that are differentially expressed in the colon of patients with Crohn's disease or SpA. These clones, with appropriate controls (6779 in total), were used to construct a glass‐based microarray, which was then used to analyse colon biopsy specimens from 15 patients with SpA, 11 patients with Crohn's disease and 10 controls. Results 95 genes were identified as differentially expressed in patients with SpA having a history of subclinical chronic gut inflammation and also in patients with Crohn's disease. Principal component analysis of this filtered set of genes successfully distinguished colon biopsy specimens from the three groups studied. Patients with SpA having subclinical chronic gut inflammation cluster together and are more related to those with Crohn's disease. Conclusion The transcriptome in the intestine of patients with SpA differs from that of controls. Moreover, these gene changes are comparable to those seen in patients with Crohn's disease, confirming initial clinical observations. On the basis of these findings, new (genetic) markers for detection of early Crohn's disease in patients with SpA can be considered. PMID:16476712

CMV sinusitis as the initial manifestation of AIDS.

PubMed

Jütte, A; Fätkenheuer, G; Hell, K; Salzberger, B

2000-03-01

Cytomegalovirus (CMV) disease is a typical late-stage complication of AIDS. Only six cases of CMV sinusitis have been reported in the literature. This is the first case of CMV sinusitis leading to the diagnosis of HIV and CMV retinitis. Diseases of the sinonasal tract may represent an initial manifestation of HIV or AIDS.

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

75 FR 19983 - National Center for Injury Prevention and Control Initial Review Group

Federal Register 2010, 2011, 2012, 2013, 2014

2010-04-16

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Centers for Disease Control and Prevention National Center for Injury Prevention and Control Initial Review Group In accordance with section 10(a)(2) of the Federal Advisory Committee Act (Pub. L. 92-463), the Centers for Disease Control and Prevention (CDC...

75 FR 7281 - National Center for Injury Prevention and Control/Initial Review Group, (NCIPC/IRG)

Federal Register 2010, 2011, 2012, 2013, 2014

2010-02-18

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Centers for Disease Control and Prevention National Center for Injury Prevention and Control/Initial Review Group, (NCIPC/IRG) In accordance with section 10(a)(2) of the Federal Advisory Committee Act (Pub. L. 92-463), the Centers for Disease Control and...

75 FR 7150 - National Center for Injury Prevention and Control/Initial Review Group, (NCIPC/IRG)

Federal Register 2010, 2011, 2012, 2013, 2014

2010-02-17

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Centers for Disease Control and Prevention National Center for Injury Prevention and Control/Initial Review Group, (NCIPC/IRG) In accordance with section 10(a)(2) of the Federal Advisory Committee Act (Pub. L. 92-463), the Centers for Disease Control and...

75 FR 5089 - National Center for Injury Prevention and Control/Initial Review Group, (NCIPC/IRG)

Federal Register 2010, 2011, 2012, 2013, 2014

2010-02-01

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Centers for Disease Control and Prevention National Center for Injury Prevention and Control/Initial Review Group, (NCIPC/IRG) In accordance with section 10(a)(2) of the Federal Advisory Committee Act (Pub. L. 92-463), the Centers for Disease Control and...

75 FR 7284 - National Center for Injury Prevention and Control/Initial Review Group, (NCIPC/IRG)

Federal Register 2010, 2011, 2012, 2013, 2014

2010-02-18

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Centers for Disease Control and Prevention National Center for Injury Prevention and Control/Initial Review Group, (NCIPC/IRG) In accordance with section 10(a)(2) of the Federal Advisory Committee Act (Pub. L. 92-463), the Centers for Disease Control and...

77 FR 3479 - National Institute of Diabetes and Digestive and Kidney Diseases Notice of Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2012-01-24

... Digestive and Kidney Diseases Initial Review Group; Diabetes, Endocrinology and Metabolic Diseases B... Program Nos. 93.847, Diabetes, Endocrinology and Metabolic Research; 93.848, Digestive Diseases and...

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.

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

Effect of glatiramer acetate on disease reactivation in MS patients discontinuing natalizumab.

PubMed

Rossi, S; Motta, C; Studer, V; De Chiara, V; Barbieri, F; Monteleone, F; Fornasiero, A; Coarelli, G; Bernardi, G; Cutter, G; Stüve, O; Salvetti, M; Centonze, D

2013-01-01

Multiple sclerosis (MS) patients discontinuing natalizumab are at risk of rebound of disease activity. In the present multi-center, open-label, non-randomized, prospective, pilot study, we tested whether treatment with glatiramer acetate (GA) is safe and effective after natalizumab in MS patients. The study was performed at academic tertiary medical centers. Forty active relapsing-remitting MS patients who never failed GA therapy and who discontinued natalizumab after 12-18 months of therapy were enrolled. GA was initiated 4 weeks after the last dose of natalizumab. 62.5% of patients were relapse-free 12 months after GA initiation. Annualized relapse rate and time to relapse were significantly lower than before natalizumab. Notably, the frequency of relapses was significantly lower amongst those patients who had experienced ≤2 relapses the year before initiation of natalizumab therapy, compared with patients who had had three or more relapses. No evidence of rebound was observed in magnetic resonance imaging scans. Furthermore, Expanded Disability Status Scale and Multiple Sclerosis Functional Composite were stable in our patients, again suggesting that 12 months of post-natalizumab-GA therapy is not associated with clinical deterioration. Following discontinuation of natalizumab, 12 months of therapy with GA is safe and well tolerated in MS patients. GA can reduce the risk of early reactivation/rebound of disease activity in this setting. © 2012 The Author(s) European Journal of Neurology © 2012 EFNS.

Functional Roles of Syk in Macrophage-Mediated Inflammatory Responses

PubMed Central

Yi, Young-Su; Son, Young-Jin; Ryou, Chongsuk; Sung, Gi-Ho; Kim, Jong-Hoon; Cho, Jae Youl

2014-01-01

Inflammation is a series of complex biological responses to protect the host from pathogen invasion. Chronic inflammation is considered a major cause of diseases, such as various types of inflammatory/autoimmune diseases and cancers. Spleen tyrosine kinase (Syk) was initially found to be highly expressed in hematopoietic cells and has been known to play crucial roles in adaptive immune responses. However, recent studies have reported that Syk is also involved in other biological functions, especially in innate immune responses. Although Syk has been extensively studied in adaptive immune responses, numerous studies have recently presented evidence that Syk has critical functions in macrophage-mediated inflammatory responses and is closely related to innate immune response. This review describes the characteristics of Syk-mediated signaling pathways, summarizes the recent findings supporting the crucial roles of Syk in macrophage-mediated inflammatory responses and diseases, and discusses Syk-targeted drug development for the therapy of inflammatory diseases. PMID:25045209

Recent sexually transmitted disease prevention efforts and their implications for AIDS health education.

PubMed

Solomon, M Z; DeJong, W

1986-01-01

In the absence of a cure or vaccine for acquired immune deficiency syndrome (AIDS) educational and social marketing efforts to reduce the transmission of Human T-lymphotropic type III/lymphadenopathy-associated virus (HTLV-III/LAV) are currently our best hope for controlling the disease. Since 1983, the Centers for Disease Control (CDC) has funded a series of research studies to determine whether education efforts can successfully motivate the adoption of key behaviors relevant to the control of a variety of sexually transmitted diseases (STDs). Analysis of the first two studies which are now completed, and preliminary data from a third study, have documented dramatic changes in behavior, knowledge, and attitudes among clients in inner-city public health clinics. The authors describe the principles and underlying assumptions that have guided the design of their STD initiatives, drawing special attention to the implications for AIDS health education efforts.

Legionella pneumonia in the Niagara Region, Ontario, Canada: a case series.

PubMed

Cargnelli, Stephanie; Powis, Jeff; Tsang, Jennifer L Y

2016-12-01

Legionella pneumophila, a major cause of Legionnaires' disease, accounts for 2-15 % of all community-acquired pneumonia requiring hospitalization and up to 30 % of community-acquired pneumonia requiring intensive care unit admission. Early initiation of appropriate antimicrobial therapy is a crucial step in the prevention of morbidity and mortality. However, recognition of Legionnaires' disease continues to be challenging because of its nonspecific clinical features. We sought to describe hospitalized community-acquired Legionnaires' disease to increase awareness of this important and potentially lethal disease. A retrospective multicenter observational study was conducted with all patients with confirmed Legionnaires' disease in the Niagara Region of the Province of Ontario, Canada, from June to December 2013. From June to December 2013, there were 14 hospitalized cases of Legionnaires' disease in the Niagara Region. Of these, 86 % (12 patients) had at least one comorbidity and 71 % (10 patients) were cigarette smokers. In our cohort, Legionnaires' disease was diagnosed with a combination of a urinary Legionella antigen test and a Legionella real-time polymerase chain reaction assay. Delay in effective antimicrobial therapy in the treatment of Legionella infection led to clinical deterioration. The majority of patients had met systemic inflammatory response syndrome criteria with fever >38 °C (71 %), heart rate >90 beats per minute (71 %), and respiratory rate >20 breaths per minute (86 %). Eleven patients (79 %) required admission to the intensive care unit or step-down unit, and nine patients (64 %) required intubation. Clinical improvement after initiation of antimicrobials was protracted. Legionnaires' disease should be considered during the late spring and summer months in patients with a history of tobacco use and various comorbidities. Clinically, patients presented with severe, nonspecific, multisystem disease characterized by shortness of breath, abnormal vital signs, and laboratory derangements including hyponatremia, elevated creatine kinase, and evidence of organ dysfunction. In addition, antimicrobial therapy with newer macrolides or respiratory fluoroquinolones should be initiated for severe community-acquired pneumonia requiring intensive care unit admission, prior to laboratory confirmation of diagnosis, especially when a clinical suspicion of Legionella infection exists.

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.

Genetics of liver disease: From pathophysiology to clinical practice.

PubMed

Karlsen, Tom H; Lammert, Frank; Thompson, Richard J

2015-04-01

Paralleling the first 30 years of the Journal of Hepatology we have witnessed huge advances in our understanding of liver disease and physiology. Genetic advances have played no small part in that. Initial studies in the 1970s and 1980s identified the strong major histocompatibility complex associations in autoimmune liver diseases. During the 1990 s, developments in genomic technologies drove the identification of genes responsible for Mendelian liver diseases. Over the last decade, genome-wide association studies have allowed for the dissection of the genetic susceptibility to complex liver disorders, in which also environmental co-factors play important roles. Findings have allowed the identification and elaboration of pathophysiological processes, have indicated the need for reclassification of liver diseases and have already pointed to new disease treatments. In the immediate future genetics will allow further stratification of liver diseases and contribute to personalized medicine. Challenges exist with regard to clinical implementation of rapidly developing technologies and interpretation of the wealth of accumulating genetic data. The historical perspective of genetics in liver diseases illustrates the opportunities for future research and clinical care of our patients. Copyright © 2015 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Elucidating the triggers, progression, and effects of Alzheimer's disease.

PubMed

Medeiros, Rodrigo; Chabrier, Meredith A; LaFerla, Frank M

2013-01-01

As the number of patients with Alzheimer's disease (AD) continues to rise, the need for efficacious therapeutics is becoming more and more urgent. Understanding the molecular relationship and interactions between Aβ and tau and their contribution to cognitive decline remain one of the most fundamental and unresolved questions in the AD field. Likewise, elucidating the initial triggers of disease pathology, as well as the impact of various factors such as stress and inflammation on disease progression, are equally important to fully understand this devastating disorder. Here we discuss recent studies that have illuminated the importance of key facilitators of disease progression using the 3xTg-AD and CaM/Tet-DTA mouse models, and suggest viable targets for ameliorating both molecular pathology and cognitive decline.

Monte Carlo simulation of the transmission of measles: Beyond the mass action principle

NASA Astrophysics Data System (ADS)

Zekri, Nouredine; Clerc, Jean Pierre

2002-04-01

We present a Monte Carlo simulation of the transmission of measles within a population sample during its growing and equilibrium states by introducing two different vaccination schedules of one and two doses. We study the effects of the contact rate per unit time ξ as well as the initial conditions on the persistence of the disease. We found a weak effect of the initial conditions while the disease persists when ξ lies in the range 1/L-10/L (L being the latent period). Further comparison with existing data, prediction of future epidemics and other estimations of the vaccination efficiency are provided. Finally, we compare our approach to the models using the mass action principle in the first and another epidemic region and found the incidence independent of the number of susceptibles after the epidemic peak while it strongly fluctuates in its growing region. This method can be easily applied to other human, animal, and plant diseases and includes more complicated parameters.

Transferring disease management and health promotion programs to other countries: critical success factors.

PubMed

Azarmina, Pejman; Prestwich, Graham; Rosenquist, Joel; Singh, Debbie

2008-12-01

Governments and health service providers around the world are under pressure to improve health outcomes while containing rising healthcare costs. In response to such challenges, many regions have implemented services that have been successful in other countries-but 'importing' initiatives has many challenges. This article summarizes factors found to be critical to the success of adapting a US disease management and health promotion programme for use in Italy and the UK. Using three illustrative case studies, it describes how in each region the programme needed to adapt (i) the form and content of the disease management service, (ii) the involvement and integration with local clinicians and services and (iii) the evaluation of programme outcomes. We argue that it is important to implement evidence-based practice by learning lessons from other countries and service initiatives, but that it is equally important to take into consideration the '3Ps' that are critical for successful service implementation: payers, practitioners and patients.

Quality indicators in inflammatory bowel disease.

PubMed

Berry, Sameer K; Melmed, Gil Y

2018-01-01

Inflammatory bowel disease (IBD), which includes Crohn's disease and ulcerative colitis, is a chronic, debilitating, and expensive condition affecting millions of people globally. There is significant variation in the quality of care for patients with IBD across North America, Europe, and Asia; this variation suggests poor quality of care due to overuse, underuse, or misuse of health services and disparity of outcomes. Several initiatives have been developed to reduce variation in care delivery and improve processes of care, patient outcomes, and reduced healthcare costs. These initiatives include the development of quality indicator sets to standardize care across organizations, and learning health systems to enable data sharing between doctors and patients, and sharing of best practices among providers. These programs have been variably successful in improving patient outcomes and reducing healthcare utilization. Further studies are needed to demonstrate the long-term impact and applicability of these efforts in different geographic areas around the world, as regional variations in patient populations, societal preferences, and costs should inform local quality improvement efforts.

Loss of anion transport without increased sodium absorption characterizes newborn porcine cystic fibrosis airway epithelia

PubMed Central

Chen, Jeng-Haur; Stoltz, David A.; Karp, Philip H.; Ernst, Sarah E.; Pezzulo, Alejandro A.; Moninger, Thomas O.; Rector, Michael V.; Reznikov, Leah R.; Launspach, Janice L.; Chaloner, Kathryn; Zabner, Joseph; Welsh, Michael J.

2011-01-01

SUMMARY Defective transepithelial electrolyte transport is thought to initiate cystic fibrosis (CF) lung disease. Yet, how loss of CFTR affects electrolyte transport remains uncertain. CFTR−/− pigs spontaneously develop lung disease resembling human CF. At birth, their airways exhibit a bacterial host defense defect, but are not inflamed. Therefore, we studied ion transport in newborn nasal and tracheal/bronchial epithelia in tissue, cultures, and in vivo. CFTR−/− epithelia showed markedly reduced Cl− and HCO3− transport. However, in contrast to a widely held view, lack of CFTR did not increase transepithelial Na+ or liquid absorption or reduce periciliary liquid depth. Like human CF, CFTR−/− pigs showed increased amiloride-sensitive voltage and current, but lack of apical Cl− conductance caused the change, not increased Na+ transport. These results indicate that CFTR provides the predominant transcellular pathway for Cl− and HCO3− in porcine airway epithelia, and reduced anion permeability may initiate CF airway disease. PMID:21145458

Hemorrhagic Tamponade as Initial Manifestation of Systemic Lupus with Subsequent Refractory and Progressive Lupus Myocarditis Resulting in Cardiomyopathy and Mitral Regurgitation.

PubMed

Marijanovich, Nicole; Halalau, Alexandra

2018-01-01

Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease with a wide range of clinical and serological manifestations. Cardiac disease among patients with SLE is common and can involve the pericardium, myocardium, valves, conduction system, and coronary arteries. We are reporting a case of SLE in a young woman that is unique is unique in that initial symptoms consisted of pericarditis and hemorrhagic tamponade which remained progressive and resistant to aggressive immunosuppressive treatment and led to severe cardiomyopathy (ejection fraction of 25%) and severe (+4) mitral regurgitation. Her immunosuppressive treatment included hydroxychloroquine, high-dose steroids, intravenous immunoglobulins, azathioprine, and mycophenolate mofetil. Her disease progression was felt to be due to underlying uncontrolled SLE because the complement levels remained persistently low throughout the entire course and PET Myocardial Perfusion and Viability study showed stable persistent active inflammation. Eventually, she was treated with cyclophosphamide which led to improvement in ejection fraction to 55% with only mild mitral regurgitation.

Hemorrhagic Tamponade as Initial Manifestation of Systemic Lupus with Subsequent Refractory and Progressive Lupus Myocarditis Resulting in Cardiomyopathy and Mitral Regurgitation

PubMed Central

Marijanovich, Nicole

2018-01-01

Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease with a wide range of clinical and serological manifestations. Cardiac disease among patients with SLE is common and can involve the pericardium, myocardium, valves, conduction system, and coronary arteries. We are reporting a case of SLE in a young woman that is unique is unique in that initial symptoms consisted of pericarditis and hemorrhagic tamponade which remained progressive and resistant to aggressive immunosuppressive treatment and led to severe cardiomyopathy (ejection fraction of 25%) and severe (+4) mitral regurgitation. Her immunosuppressive treatment included hydroxychloroquine, high-dose steroids, intravenous immunoglobulins, azathioprine, and mycophenolate mofetil. Her disease progression was felt to be due to underlying uncontrolled SLE because the complement levels remained persistently low throughout the entire course and PET Myocardial Perfusion and Viability study showed stable persistent active inflammation. Eventually, she was treated with cyclophosphamide which led to improvement in ejection fraction to 55% with only mild mitral regurgitation. PMID:29610699

Effectiveness of Emergency Department Based Palliative Care for Adults with Advanced Disease: A Systematic Review

PubMed Central

Nunes, Cristina Moura; Gomes, Barbara

2016-01-01

Abstract Background: Emergency departments (EDs) are seeing more patients with palliative care (PC) needs, but evidence on best practice is scarce. Objectives: To examine the effectiveness of ED-based PC interventions on hospital admissions (primary outcome), length of stay (LOS), symptoms, quality of life, use of other health care services, and PC referrals for adults with advanced disease. Methods: We searched five databases until August 2014, checked reference lists/conference abstracts, and contacted experts. Eligible studies were controlled trials, pre-post studies, cohort studies, and case series reporting outcomes of ED-based PC. Results: Five studies with 4374 participants were included: three case series and two cohort studies. Interventions included a screening tool, traditional ED-PC, and integrated ED-PC. Two studies reported on hospital admissions: in one study there was no statistically significant difference in 90-day readmission rates between patients who initiated integrated PC at the ED (11/50 patients, 22%) compared to those who initiated PC after hospital admission (179/1385, 13%); another study showed a high admission rate (90%) in 14 months following ED-PC, but without comparison. One study showed an LOS reduction (mean 4.32 days in ED-initiated PC group versus 8.29 days in postadmission-initiated group; p < 0.01). There was scarce evidence on other outcomes except for conflicting findings on survival: in one study, ED-PC patients were more likely to experience an interval between ED presentation and death >9 hours (OR 2.75, 95% CI 2.21–3.41); another study showed increased mortality risk in the intervention group; and a case series described a higher in-hospital death rate when PC was ED-initiated (62%), compared to ward (16%) or ICU (50%) (unknown p-value). Conclusions: There is yet no evidence that ED-based PC affects patient outcomes except for indication from one study of no association with 90-day hospital readmission but a possible reduction in LOS if integrated PC is introduced early at ED rather than after hospital admission. There is an urgent need for trials to confirm these findings alongside other potential benefits and survival effects. PMID:27115914

Parameters indicative of persistence of valvular pathology at initial diagnosis in acute rheumatic carditis: the role of albumin and CD19 expression.

PubMed

Oner, Taliha; Ozdemir, Rahmi; Genc, Dildar Bahar; Kucuk, Mehmet; Karadeniz, Cem; Demirpence, Savas; Yilmazer, Murat Muhtar; Mese, Timur; Tavli, Vedide; Genel, Ferah

The aim of this study is to define the predictors of chronic carditis in patients with acute rheumatic carditis (ARC). Patients diagnosed with ARC between May 2010 and May 2011 were included in the study. Echocardiography, electrocardiography, lymphocyte subset analysis, acute phase reactants, plasma albumin levels, and antistreptolysin-O (ASO) tests were performed at initial presentation. The echocardiographic assessments were repeated at the sixth month of follow-up. The patients were divided into two groups according to persistence of valvular pathology at 6th month as Group 1 and Group 2, and all clinical and laboratory parameters at admission were compared between two groups of valvular involvement. During the one-year study period, 22 patients had valvular disease. Seventeen (77.2%) patients showed regression in valvular pathology. An initial mild regurgitation disappeared in eight patients (36.3%). Among seven (31.8%) patients with moderate regurgitation initially, the regurgitation disappeared in three, and four patients improved to mild regurgitation. Two patients with a severe regurgitation initially improved to moderate regurgitation (9.1%). In five (22.8%) patients, the grade of regurgitation [moderate regurgitation in one (4.6%), and severe regurgitation in 4 (18.2%)] remained unchanged. The albumin level was significantly lower at diagnosis in Group 2 (2.6±0.48g/dL). Lymphocyte subset analysis showed a significant decrease in the CD8 percentage and a significant increase in CD19 percentage at diagnosis in Group 2 compared to Group 1. The blood albumin level and the percentage of CD8 and CD19 (+) lymphocytes at diagnosis may help to predict chronic valvular disease risk in patients with acute rheumatic carditis. Copyright © 2016. Published by Elsevier Editora Ltda.

The role of transnational mobility in the local spread of mosquito-borne disease: Measuring the determinants of spatial-temporal lags of imported dengue cases initiating indigenous epidemics in Taiwan

NASA Astrophysics Data System (ADS)

Wen, Tzai-Hung

2014-05-01

Dengue fever is one of the world's most widely spread mosquito-borne diseases. International travelers who acquire dengue infection are important routes for virus transmission from one country to another one. Previous studies have shown that imported dengue cases are able to initiate indigenous epidemics when appropriate weather conditions are present. However, the spatial-temporal associations between imported cases and indigenous epidemics in areas with different social-economic conditions are still unclear. This study investigated determinants of spatial-temporal lags of imported dengue cases who initiated indigenous epidemics from 2003 to 2012 in Taiwan. The quantile regression is used to explore the associations between spatial-temporal lags of imported cases and social-economic indicators with geographic heterogeneity. Our results indicated that imported cases in April and May have statistically significant contribution to initiate indigenous epidemics. Areas with high population density and low average income have significant risk of being imported virus from other areas. However, the areas with imported cases are not significant transmission risk. The results imply that imported cases reported in early summer may be an early-warning indicator of indigenous epidemics. Local demographic and economic conditions, rather than imported cases, may determine the areas with the risk of indigenous epidemics.

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.

Physical inactivity and obesity: relation to asthma and chronic obstructive pulmonary disease?

PubMed

ten Hacken, Nick H T

2009-12-01

Physical inactivity and obesity are modifiable risk factors for many chronic diseases, including cardiovascular disease, diabetes mellitus, osteoporosis, osteoarthritis, and depression. Both physical inactivity and obesity are associated with low-grade systemic inflammation that may contribute to the inflammatory processes present in many chronic diseases. In asthma, almost no studies are available in which physical inactivity has been studied using performance-based instruments. In contrast, the association between obesity and a higher prevalence of asthma has often been suggested in a large number of studies. In chronic obstructive pulmonary disease (COPD) physical inactivity has been demonstrated in a few studies that used performance-based instruments; this was associated with the higher COPD Global Initiative on Obstructive Lung Disease (GOLD) stages and a higher degree of systemic inflammation, independent of body mass index. In contrast to physical inactivity, obesity in COPD is associated with the lower GOLD stages. Additionally, obesity is associated with the chronic obstructive phenotype and features of the metabolic syndrome. To elucidate the independent relation of physical inactivity and obesity with systemic inflammation, performance-based studies of physical inactivity in asthma and COPD are highly needed.

Humoral Epitope Spreading in Autoimmune Bullous Diseases

PubMed Central

Didona, Dario; Di Zenzo, Giovanni

2018-01-01

Autoimmune blistering diseases are characterized by autoantibodies against structural adhesion proteins of the skin and mucous membranes. Extensive characterization of their autoantibody targets has improved understanding of pathogenesis and laid the basis for the study of antigens/epitopes diversification, a process termed epitope spreading (ES). In this review, we have reported and discussed ES phenomena in autoimmune bullous diseases and underlined their functional role in disease pathogenesis. A functional ES has been proposed: (1) in bullous pemphigoid patients and correlates with the initial phase of the disease, (2) in pemphigus vulgaris patients with mucosal involvement during the clinical transition to a mucocutaneous form, (3) in endemic pemphigus foliaceus, underlining its role in disease pathogenesis, and (4) in numerous cases of disease transition associated with an intermolecular diversification of immune response. All these findings could give useful information to better understand autoimmune disease pathogenesis and to design antigen/epitope specific therapeutic approaches. PMID:29719538

Diagnosis of Parkinson's disease on the basis of clinical and genetic classification: a population-based modelling study.

PubMed

Nalls, Mike A; McLean, Cory Y; Rick, Jacqueline; Eberly, Shirley; Hutten, Samantha J; Gwinn, Katrina; Sutherland, Margaret; Martinez, Maria; Heutink, Peter; Williams, Nigel M; Hardy, John; Gasser, Thomas; Brice, Alexis; Price, T Ryan; Nicolas, Aude; Keller, Margaux F; Molony, Cliona; Gibbs, J Raphael; Chen-Plotkin, Alice; Suh, Eunran; Letson, Christopher; Fiandaca, Massimo S; Mapstone, Mark; Federoff, Howard J; Noyce, Alastair J; Morris, Huw; Van Deerlin, Vivianna M; Weintraub, Daniel; Zabetian, Cyrus; Hernandez, Dena G; Lesage, Suzanne; Mullins, Meghan; Conley, Emily Drabant; Northover, Carrie A M; Frasier, Mark; Marek, Ken; Day-Williams, Aaron G; Stone, David J; Ioannidis, John P A; Singleton, Andrew B

2015-10-01

Accurate diagnosis and early detection of complex diseases, such as Parkinson's disease, has the potential to be of great benefit for researchers and clinical practice. We aimed to create a non-invasive, accurate classification model for the diagnosis of Parkinson's disease, which could serve as a basis for future disease prediction studies in longitudinal cohorts. We developed a model for disease classification using data from the Parkinson's Progression Marker Initiative (PPMI) study for 367 patients with Parkinson's disease and phenotypically typical imaging data and 165 controls without neurological disease. Olfactory function, genetic risk, family history of Parkinson's disease, age, and gender were algorithmically selected by stepwise logistic regression as significant contributors to our classifying model. We then tested the model with data from 825 patients with Parkinson's disease and 261 controls from five independent cohorts with varying recruitment strategies and designs: the Parkinson's Disease Biomarkers Program (PDBP), the Parkinson's Associated Risk Study (PARS), 23andMe, the Longitudinal and Biomarker Study in PD (LABS-PD), and the Morris K Udall Parkinson's Disease Research Center of Excellence cohort (Penn-Udall). Additionally, we used our model to investigate patients who had imaging scans without evidence of dopaminergic deficit (SWEDD). In the population from PPMI, our initial model correctly distinguished patients with Parkinson's disease from controls at an area under the curve (AUC) of 0·923 (95% CI 0·900-0·946) with high sensitivity (0·834, 95% CI 0·711-0·883) and specificity (0·903, 95% CI 0·824-0·946) at its optimum AUC threshold (0·655). All Hosmer-Lemeshow simulations suggested that when parsed into random subgroups, the subgroup data matched that of the overall cohort. External validation showed good classification of Parkinson's disease, with AUCs of 0·894 (95% CI 0·867-0·921) in the PDBP cohort, 0·998 (0·992-1·000) in PARS, 0·955 (no 95% CI available) in 23andMe, 0·929 (0·896-0·962) in LABS-PD, and 0·939 (0·891-0·986) in the Penn-Udall cohort. Four of 17 SWEDD participants who our model classified as having Parkinson's disease converted to Parkinson's disease within 1 year, whereas only one of 38 SWEDD participants who were not classified as having Parkinson's disease underwent conversion (test of proportions, p=0·003). Our model provides a potential new approach to distinguish participants with Parkinson's disease from controls. If the model can also identify individuals with prodromal or preclinical Parkinson's disease in prospective cohorts, it could facilitate identification of biomarkers and interventions. National Institute on Aging, National Institute of Neurological Disorders and Stroke, and the Michael J Fox Foundation. Copyright © 2015 Elsevier Ltd. All rights reserved.

Knowledge and Behavioral Effects in Cardiovascular Health: Community Health Worker Health Disparities Initiative, 2007–2010

PubMed Central

Hurtado, Margarita; Yang, Manshu; Evensen, Christian; Windham, Amy; Ortiz, Gloria; Tracy, Rachel; Ivy, Edward Donnell

2014-01-01

Introduction Cardiovascular disease is the leading cause of death in the United States, and disparities in cardiovascular health exist among African Americans, American Indians, Hispanics, and Filipinos. The Community Health Worker Health Disparities Initiative of the National Heart, Lung, and Blood Institute (NHLBI) includes culturally tailored curricula taught by community health workers (CHWs) to improve knowledge and heart-healthy behaviors in these racial/ethnic groups. Methods We used data from 1,004 community participants in a 10-session curriculum taught by CHWs at 15 sites to evaluate the NHLBI’s health disparities initiative by using a 1-group pretest–posttest design. The curriculum addressed identification and management of cardiovascular disease risk factors. We used linear mixed effects and generalized linear mixed effects models to examine results. Results Average participant age was 48; 75% were female, 50% were Hispanic, 35% were African American, 8% were Filipino, and 7% were American Indian. Twenty-three percent reported a history of diabetes, and 37% reported a family history of heart disease. Correct pretest to posttest knowledge scores increased from 48% to 74% for heart healthy knowledge. The percentage of participants at the action or maintenance stage of behavior change increased from 41% to 85%. Conclusion Using the CHW model to implement community education with culturally tailored curricula may improve heart health knowledge and behaviors among minorities. Further studies should examine the influence of such programs on clinical risk factors for cardiovascular disease. PMID:24524426

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

Programming and execution of movement in Parkinson's disease.

PubMed

Sheridan, M R; Flowers, K A; Hurrell, J

1987-10-01

Programming and execution of arm movements in Parkinson's disease were investigated in choice and simple reaction time (RT) situations in which subjects made aimed movements at a target. A no-aiming condition was also studied. Reaction time was fractionated using surface EMG recording into premotor (central) and motor (peripheral) components. Premotor RT was found to be greater for parkinsonian patients than normal age-matched controls in the simple RT condition, but not in the choice condition. This effect did not depend on the parameters of the impending movement. Thus, paradoxically, parkinsonian patients were not inherently slower at initiating aiming movements from the starting position, but seemed unable to use advance information concerning motor task demands to speed up movement initiation. For both groups, low velocity movements took longer to initiate than high velocity ones. In the no-aiming condition parkinsonian RTs were markedly shorter than when aiming, but were still significantly longer than control RTs. Motor RT was constant across all conditions and was not different for patient and control subjects. In all conditions, parkinsonian movements were around 37% slower than control movements, and their movement times were more variable, the differences showing up early on in the movement, that is, during the initial ballistic phase. The within-subject variability of movement endpoints was also greater in patients. The motor dysfunction displayed in Parkinson's disease involves a number of components: (1) a basic central problem with simply initiating movements, even when minimal programming is required (no-aiming condition); (2) difficulty in maintaining computed forces for motor programs over time (simple RT condition); (3) a basic slowness of movement (bradykinesia) in all conditions; and (4) increased variability of movement in both time and space, presumably caused by inherent variability in force production.

Becoming the Framingham Study 1947–1950

PubMed Central

Oppenheimer, Gerald M.

2005-01-01

In the epidemiological imagination, the Framingham Heart Study has attained iconic status, both as the prototype of the cohort study and as a result of its scientific success. When the Public Health Service launched the study in 1947, epidemiological knowledge of coronary heart disease was poor, and epidemiology primarily involved the study of infectious disease. In constructing their investigation, Framingham’s initiators had to invent new approaches to epidemiological research. These scientific goals were heavily influenced by the contending institutional and personal interests buffeting the study. The study passed through vicissitudes and stages during its earliest years as its organizers grappled to define its relationship to medicine, epidemiology, and the local community. PMID:15798116

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.

Public Health Adaptation to Climate Change in Canadian Jurisdictions

PubMed Central

Austin, Stephanie E.; Ford, James D.; Berrang-Ford, Lea; Araos, Malcolm; Parker, Stephen; Fleury, Manon D.

2015-01-01

Climate change poses numerous risks to the health of Canadians. Extreme weather events, poor air quality, and food insecurity in northern regions are likely to increase along with the increasing incidence and range of infectious diseases. In this study we identify and characterize Canadian federal, provincial, territorial and municipal adaptation to these health risks based on publically available information. Federal health adaptation initiatives emphasize capacity building and gathering information to address general health, infectious disease and heat-related risks. Provincial and territorial adaptation is varied. Quebec is a leader in climate change adaptation, having a notably higher number of adaptation initiatives reported, addressing almost all risks posed by climate change in the province, and having implemented various adaptation types. Meanwhile, all other Canadian provinces and territories are in the early stages of health adaptation. Based on publically available information, reported adaptation also varies greatly by municipality. The six sampled Canadian regional health authorities (or equivalent) are not reporting any adaptation initiatives. We also find little relationship between the number of initiatives reported in the six sampled municipalities and their provinces, suggesting that municipalities are adapting (or not adapting) autonomously. PMID:25588156

Evidence for label-retaining tumour-initiating cells in human glioblastoma

PubMed Central

Deleyrolle, Loic P.; Harding, Angus; Cato, Kathleen; Siebzehnrubl, Florian A.; Rahman, Maryam; Azari, Hassan; Olson, Sarah; Gabrielli, Brian; Osborne, Geoffrey; Vescovi, Angelo

2011-01-01

Individual tumour cells display diverse functional behaviours in terms of proliferation rate, cell–cell interactions, metastatic potential and sensitivity to therapy. Moreover, sequencing studies have demonstrated surprising levels of genetic diversity between individual patient tumours of the same type. Tumour heterogeneity presents a significant therapeutic challenge as diverse cell types within a tumour can respond differently to therapies, and inter-patient heterogeneity may prevent the development of general treatments for cancer. One strategy that may help overcome tumour heterogeneity is the identification of tumour sub-populations that drive specific disease pathologies for the development of therapies targeting these clinically relevant sub-populations. Here, we have identified a dye-retaining brain tumour population that displays all the hallmarks of a tumour-initiating sub-population. Using a limiting dilution transplantation assay in immunocompromised mice, label-retaining brain tumour cells display elevated tumour-initiation properties relative to the bulk population. Importantly, tumours generated from these label-retaining cells exhibit all the pathological features of the primary disease. Together, these findings confirm dye-retaining brain tumour cells exhibit tumour-initiation ability and are therefore viable targets for the development of therapeutics targeting this sub-population. PMID:21515906

SNPing Away at Complex Diseases: Analysis of Single-Nucleotide Polymorphisms around APOE in Alzheimer Disease

PubMed Central

Martin, Eden R.; Lai, Eric H.; Gilbert, John R.; Rogala, Allison R.; Afshari, A. J.; Riley, John; Finch, K. L.; Stevens, J. F.; Livak, K. J.; Slotterbeck, Brandon D.; Slifer, Susan H.; Warren, Liling L.; Conneally, P. Michael; Schmechel, Donald E.; Purvis, Ian; Pericak-Vance, Margaret A.; Roses, Allen D.; Vance, Jeffery M.

2000-01-01

There has been great interest in the prospects of using single-nucleotide polymorphisms (SNPs) in the search for complex disease genes, and several initiatives devoted to the identification and mapping of SNPs throughout the human genome are currently underway. However, actual data investigating the use of SNPs for identification of complex disease genes are scarce. To begin to look at issues surrounding the use of SNPs in complex disease studies, we have initiated a collaborative SNP mapping study around APOE, the well-established susceptibility gene for late-onset Alzheimer disease (AD). Sixty SNPs in a 1.5-Mb region surrounding APOE were genotyped in samples of unrelated cases of AD, in controls, and in families with AD. Standard tests were conducted to look for association of SNP alleles with AD, in cases and controls. We also used family-based association analyses, including recently developed methods to look for haplotype association. Evidence of association (P⩽.05) was identified for 7 of 13 SNPs, including the APOE-4 polymorphism, spanning 40 kb on either side of APOE. As expected, very strong evidence for association with AD was seen for the APOE-4 polymorphism, as well as for two other SNPs that lie <16 kb from APOE. Haplotype analysis using family data increased significance over that seen in single-locus tests for some of the markers, and, for these data, improved localization of the gene. Our results demonstrate that associations can be detected at SNPs near a complex disease gene. We found that a high density of markers will be necessary in order to have a good chance of including SNPs with detectable levels of allelic association with the disease mutation, and statistical analysis based on haplotypes can provide additional information with respect to tests of significance and fine localization of complex disease genes. PMID:10869235

SNPing away at complex diseases: analysis of single-nucleotide polymorphisms around APOE in Alzheimer disease.

PubMed

Martin, E R; Lai, E H; Gilbert, J R; Rogala, A R; Afshari, A J; Riley, J; Finch, K L; Stevens, J F; Livak, K J; Slotterbeck, B D; Slifer, S H; Warren, L L; Conneally, P M; Schmechel, D E; Purvis, I; Pericak-Vance, M A; Roses, A D; Vance, J M

2000-08-01

There has been great interest in the prospects of using single-nucleotide polymorphisms (SNPs) in the search for complex disease genes, and several initiatives devoted to the identification and mapping of SNPs throughout the human genome are currently underway. However, actual data investigating the use of SNPs for identification of complex disease genes are scarce. To begin to look at issues surrounding the use of SNPs in complex disease studies, we have initiated a collaborative SNP mapping study around APOE, the well-established susceptibility gene for late-onset Alzheimer disease (AD). Sixty SNPs in a 1.5-Mb region surrounding APOE were genotyped in samples of unrelated cases of AD, in controls, and in families with AD. Standard tests were conducted to look for association of SNP alleles with AD, in cases and controls. We also used family-based association analyses, including recently developed methods to look for haplotype association. Evidence of association (P

[Sense of smell, physiological ageing and neurodegenerative diseases: II. Ageing and neurodegenerative diseases].

PubMed

Fusari, A; Molina, J A

The sense of smell, which was once studied because of its biological and evolutionary significance, is today one of the centres of interest in research on normal and pathological ageing. The latest scientific developments point to an inversely proportional relationship between age and olfactory sensitivity. In certain neurodegenerative diseases this sensory decline is one of the first symptoms of the disorder and is correlated with the progression of the disease. In this work we are going to review the scientific knowledge on loss of sense of smell in ageing and in neurodegenerative diseases, with special attention given to Alzheimer's and Parkinson's diseases. A survey of studies that have examined the olfactory deficits in ageing and in some neurodegenerative diseases offers conclusive results about the presence of these impairments in the early stages of these disorders and even among healthy elderly persons. Although a number of causes contribute to these sensory losses in physiological ageing, a common neurological foundation has been proposed for Alzheimer's and Parkinson's diseases. Nevertheless, despite certain initial similarities, the olfactory deficits shown in these disorders seem to be qualitatively different.

Temporal Regulation by Innate Type 2 Cytokines in Food Allergies.

PubMed

Graham, Michelle T; Andorf, Sandra; Spergel, Jonathan M; Chatila, Talal A; Nadeau, Kari C

2016-10-01

Food allergies (FAs) are a growing epidemic in western countries with poorly defined etiology. Defined as an adverse immune response to common food allergens, FAs present heterogeneously as a single- or multi-organ response that ranges in severity from localized hives and angioedema to systemic anaphylaxis. Current research focusing on epithelial-derived cytokines contends that temporal regulation by these factors impact initial sensitization and persistence of FA responses upon repeated food allergen exposure. Mechanistic understanding of FA draws insight from a myriad of atopic conditions studied in humans and modeled in mice. In this review, we will highlight how epithelial-derived cytokines initiate and then potentiate FAs. We will also review existing evidence of the contribution of other atopic diseases to FA pathogenesis and whether FA symptoms overlap with other atopic diseases.

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 paradoxical kinesis in the laboratory under both self-initiated and externally-triggered conditions has implications for motivational and attentional enhancement of movement speed in Parkinson’s disease. PMID:26284366

Association of complementary and alternative medicine use with highly active antiretroviral therapy initiation.

PubMed

Merenstein, Daniel; Yang, Yang; Schneider, Michael F; Goparaju, Lakshmi; Weber, Kathleen; Sharma, Anjali; Levine, Alexandra M; Sharp, Gerald B; Gandhi, Monica; Liu, Chenglong

2008-01-01

To assess whether complementary and alternative medicine (CAM) use is associated with the timing of highly active antiretroviral therapy (HAART) initiation among human immunodeficiency virus (HIV)-infected participants of the Women's Interagency HIV Study. Prospective cohort study between January 1996 and March 2002. Differences in the cumulative incidence of HAART initiation were compared between CAM users and non-CAM users using a logrank test. Cox regression model was used to assess associations of CAM exposures with time to HAART initiation. MAIN OUTCOME AND EXPOSURES: Study outcome was time from January 1996 to initiation of HAART. Primary exposure was use of any CAM modality before January 1996, and secondary exposures included the number and type of CAM modalities used (ingestible CAM medication, body practice, or spiritual healing) during the same period. One thousand thirty-four HIV-infected women contributed a total of 4987 person-visits during follow-up. At any time point, the cumulative incidence of HAART initiation among CAM users was higher than that among non-CAM users. After adjustment for potential confounders, those reporting CAM use were 1.34 times (95% confidence interval: 1.09, 1.64) more likely to initiate HAART than non-CAM users. Female CAM users initiated HAART regimens earlier than non-CAM users. Initiation of HAART is an important clinical marker, but more research is needed to elucidate the role specific CAM modalities play in HIV disease progression.

Delay of Treatment Initiation Does Not Adversely Affect Survival Outcome in Breast Cancer.

PubMed

Yoo, Tae-Kyung; Han, Wonshik; Moon, Hyeong-Gon; Kim, Jisun; Lee, Jun Woo; Kim, Min Kyoon; Lee, Eunshin; Kim, Jongjin; Noh, Dong-Young

2016-07-01

Previous studies examining the relationship between time to treatment and survival outcome in breast cancer have shown inconsistent results. The aim of this study was to analyze the overall impact of delay of treatment initiation on patient survival and to determine whether certain subgroups require more prompt initiation of treatment. This study is a retrospective analysis of stage I-III patients who were treated in a single tertiary institution between 2005 and 2008. Kaplan-Meier survival analysis and Cox proportional hazards regression model were used to evaluate the impact of interval between diagnosis and treatment initiation in breast cancer and various subgroups. A total of 1,702 patients were included. Factors associated with longer delay of treatment initiation were diagnosis at another hospital, medical comorbidities, and procedures performed before admission for surgery. An interval between diagnosis and treatment initiation as a continuous variable or with a cutoff value of 15, 30, 45, and 60 days had no impact on disease-free survival (DFS). Subgroup analyses for hormone-responsiveness, triple-negative breast cancer, young age, clinical stage, and type of initial treatment showed no significant association between longer delay of treatment initiation and DFS. Our results show that an interval between diagnosis and treatment initiation of 60 days or shorter does not appear to adversely affect DFS in breast cancer.

76 FR 20692 - National Institute of Diabetes and Digestive and Kidney Diseases; Notice of Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2011-04-13

... Diabetes and Digestive and Kidney Diseases; Notice of Meeting Pursuant to section 10(d) of the Federal... Digestive and Kidney Diseases Initial Review Group; Diabetes, Endocrinology and Metabolic Diseases B... and Metabolic Research; 93.848, Digestive Diseases and Nutrition Research; 93.849, Kidney Diseases...

76 FR 30733 - National Institute of Diabetes and Digestive and Kidney Diseases; Notice of Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2011-05-26

... Diabetes and Digestive and Kidney Diseases; Notice of Meeting Pursuant to section 10(d) of the Federal... Digestive and Kidney Diseases Initial Review Group, Digestive Diseases and Nutrition C Subcommittee. Date... Diseases and Nutrition Research; 93.849, Kidney Diseases, Urology and Hematology Research, National...

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 Research.

Barriers to palliative care in people with chronic obstructive pulmonary disease in home care: A qualitative study of the perspective of professional caregivers.

PubMed

Mousing, Camilla A; Timm, Helle; Lomborg, Kirsten; Kirkevold, Marit

2018-02-01

To examine the experiences with palliative care in people with chronic obstructive pulmonary disease among professional caregivers in a Danish home care setting. Many patients with advanced chronic obstructive pulmonary disease depend on professional caregivers in the primary sector to provide assistance and care. However, chronic obstructive pulmonary disease patients receive no or only very little palliative care compared to patients with cancer although they may have many burdensome symptoms. Qualitative explorative study. In 2013-2014, ten professional caregivers from three districts in a Danish municipality were followed during home visits to patients with chronic obstructive pulmonary disease and individual interviews about palliative care were subsequently conducted. In 2014, 66 professional caregivers, representing eleven home care districts, participated in ten group discussions about palliative care needs in this group of patients. Data were analysed using qualitative descriptive analysis. The study revealed a nonawareness of palliative care for patients with chronic obstructive pulmonary disease among the professional caregivers who expressed vague understanding of palliative care and lack of knowledge about the disease. Organisational barriers, such as lack of time and continuity in patient care, lack of opportunity to discuss palliative care and lack of peer learning were experienced as challenging in the provision of palliative care. Nonawareness and organisational barriers led to difficulties in identifying palliative care needs and reluctance to initiate conversations about palliative care. The findings indicate a need for education, training and reflection among professional caregivers in home care. Also, organisational changes may be needed to reduce the barriers to palliative care. The findings uncovered barriers to palliative care that must be addressed. Targeted educational programmes and organisational changes may increase the ability to identify palliative care needs and initiate and evaluate palliative interventions. © 2017 John Wiley & Sons Ltd.

The "fourth disease" of childhood: reevaluation of a nonexistent disease.

PubMed

Morens, D M; Katz, A R

1991-09-15

Observed and described between 1884 and 1900, "fourth disease" (Dukes disease) followed measles, scarlet fever, and rubella as the fourth clinically characterized childhood exanthem. Like rubella ("third disease") and erythema infectiosum ("fifth disease"), accepted by the medical community at about the same time, the existence of fourth disease was initially controversial. Over the following decades descriptions of hundreds of cases, outbreaks, and laboratory studies were published in the indexed medical literature. Unlike rubella and fifth disease, however, fourth disease was not subsequently proven to exist by either epidemiologic criteria or isolation of an etiologic agent. By the 1930s, it was infrequently recognized and by the 1960s had been dropped from textbooks. In this study, the authors use epidemiologic methods to reevaluate published data on English schoolchildren from 1892 to 1900 upon which the original fourth disease claim of Dukes was based. The authors conclude that fourth disease never existed. Reinterpretation of the original data suggests that cases can be completely explained as misdiagnosed rubella and scarlet fever. Misidentification of fourth disease is attributed to failures in the critical abilities of the medical and scientific communities at the time. The implications of erroneously identifying a nonexistent disease suggest that modern scientific approaches to disease identification are sound.

Targeting the Insulin-Like Growth Factor 1 Receptor in Ewing's Sarcoma: Reality and Expectations

PubMed Central

Olmos, David; Martins, Ana Sofia; Jones, Robin L.; Alam, Salma; Scurr, Michelle; Judson, Ian R.

2011-01-01

Ewing's sarcoma family of tumours comprises a group of very aggressive diseases that are potentially curable with multimodality treatment. Despite the undoubted success of current treatment, approximately 30% of patients will relapse and ultimately die of disease. The insulin-like growth factor 1 receptor (IGF-1R) has been implicated in the genesis, growth, proliferation, and the development of metastatic disease in Ewing's sarcoma. In addition, IGF1-R has been validated, both in vitro and in vivo, as a potential therapeutic target in Ewing's sarcoma. Phase I studies of IGF-1R monoclonal antibodies reported several radiological and clinical responses in Ewing's sarcoma patients, and initial reports of several Phase II studies suggest that about a fourth of the patients would benefit from IGF-1R monoclonal antibodies as single therapy, with approximately 10% of patients achieving objective responses. Furthermore, these therapies are well tolerated, and thus far severe toxicity has been rare. Other studies assessing IGF-1R monoclonal antibodies in combination with traditional cytotoxics or other targeted therapies are expected. Despite, the initial promising results, not all patients benefit from IGF-1R inhibition, and consequently, there is an urgent need for the identification of predictive markers of response. PMID:21647361

ASSOCIATION OF COMPLEMENTARY AND ALTERNATIVE MEDICINE USE WITH HIGHLY ACTIVE ANTIRETROVIRAL THERAPY INITIATION

PubMed Central

Merenstein, Daniel; Yang, Yang; Schneider, Michael F.; Goparaju, Lakshmi; Weber, Kathleen; Sharma, Anjali; Levine, Alexandra M.; Sharp, Gerald B.; Gandhi, Monica; Liu, Chenglong

2009-01-01

Objective To assess whether complementary and alternative medicine (CAM) use is associated with the timing of highly active antiretroviral therapy (HAART) initiation among human immunodeficiency virus (HIV)–infected participants of the Women’s Interagency HIV Study. Study Methods Prospective cohort study between January 1996 and March 2002. Differences in the cumulative incidence of HAART initiation were compared between CAM users and non–CAM users using a logrank test. Cox regression model was used to assess associations of CAM exposures with time to HAART initiation. Main Outcome and Exposures Study outcome was time from January 1996 to initiation of HAART. Primary exposure was use of any CAM modality before January 1996, and secondary exposures included the number and type of CAM modalities used (ingestible CAM medication, body practice, or spiritual healing) during the same period. Results One thousand thirty-four HIV-infected women contributed a total of 4987 person-visits during follow-up. At any time point, the cumulative incidence of HAART initiation among CAM users was higher than that among non–CAM users. After adjustment for potential confounders, those reporting CAM use were 1.34 times (95% confidence interval: 1.09, 1.64) more likely to initiate HAART than non–CAM users. Conclusion Female CAM users initiated HAART regimens earlier than non–CAM users. Initiation of HAART is an important clinical marker, but more research is needed to elucidate the role specific CAM modalities play in HIV disease progression. PMID:18780580

[Development and Distribution of Drugs for NTDs: Efforts of One Pharmaceutical Company].

PubMed

Asada, Makoto

2016-01-01

The Pharmaceutical Industry is expected to play a proactive global role in combatting neglected tropical diseases (NTDs) and other tropical diseases affecting low-income countries. Such a role would include novel medicine R&D, manufacturing and distribution. In order to succeed in this role, several challenges need to be overcome: a) the economic challenge or cost benefit balance for the development of these medicines, and b) sparse in-house experience with these diseases within the Industry. During the last decade, the Product Development Partnership (PDP) model has become an effective strategy to address such challenges. Organizations such as the Medicines for Malaria Venture (MMV), Drugs for Neglected Diseases initiative (DNDi), TB alliance, PATH (formerly the Program for Appropriate Technology in Health), and others have linked pharmaceutical companies, funding organizations, academic researchers and others, and have thus been able to successfully populate treatment pipelines directed at NTDs, Malaria, tuberculosis (TB), and human immunodeficiency virus (HIV)/AIDS. In this paper, our experience working with one of these organizations, DNDi, is described. We have been collaborating with DNDi in evaluating the actions of Eisai's antifungal compound, E1224, in a clinical study for treating Chagas Disease. In addition, other Eisai initiatives directed at NTDs and improving patients' access to medicines are introduced.

Necroptosis: an emerging type of cell death in liver diseases.

PubMed

Saeed, Waqar Khalid; Jun, Dae Won

2014-09-21

Cell death has been extensively evaluated for decades and it is well recognized that pharmacological interventions directed to inhibit cell death can prevent significant cell loss and can thus improve an organ's physiological function. For long, only apoptosis was considered as a sole form of programmed cell death. Recently necroptosis, a RIP1/RIP3-dependent programmed cell death, has been identified as an apoptotic backup cell death mechanism with necrotic morphology. The evidences of necroptosis and protective effects achieved by blocking necroptosis have been extensively reported in recent past. However, only a few studies reported the evidence of necroptosis and protective effects achieved by inhibiting necroptosis in liver related disease conditions. Although the number of necroptosis initiators is increasing; however, interestingly, it is still unclear that what actually triggers necroptosis in different liver diseases or if there is always a different necroptosis initiator in each specific disease condition followed by specific downstream signaling molecules. Understanding the precise mechanism of necroptosis as well as counteracting other cell death pathways in liver diseases could provide a useful insight towards achieving extensive therapeutic significance. By targeting necroptosis and/or other parallel death pathways, a significant cell loss and thus a decrement in an organ's physiological function can be prevented.

[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.

Consensus on the criteria needed for creating a rare-disease patient registry. A Delphi study.

PubMed

Cavero-Carbonell, Clara; Gras-Colomer, Elena; Guaita-Calatrava, Rosana; López-Briones, Carmen; Amorós, Rubén; Abaitua, Ignacio; Posada, Manuel; Zurriaga, Oscar

2016-06-01

Patient registries (PRs) are important tools for public-health surveillance and rare-disease research. The purpose of this study is to identify the most important criteria for the creation of a rare-disease PR that could be used by public-health authorities to develop health policies. A consensus-development Delphi study was used, with participants selected for their expertize in rare diseases and registries. Participants were asked to complete a questionnaire on the most important criteria for creating PRs. Three rounds were performed. Agreement was reached on half the questions in the first round and on 89% of questions in the final round, with a total expert participation rate of around 60% by the final stage. This study made it possible to reach a broader consensus starting from experts' initial assessment of the features that should be considered for the creation of a rare-disease PR. The consensus method used made it possible to define the characteristics of a PR based on expert opinion within a rare-disease framework. This study may serve as a guide for helping other researchers plan and build a rare-disease PR. © The Author 2015. Published by Oxford University Press on behalf of Faculty of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Medical nutrition therapy in adults with chronic kidney disease: integrating evidence and consensus into practice for the generalist registered dietitian nutritionist.

PubMed

Beto, Judith A; Ramirez, Wendy E; Bansal, Vinod K

2014-07-01

Chronic kidney disease is classified in stages 1 to 5 by the National Kidney Foundation's Kidney Disease Outcomes Quality Initiative depending on the level of renal function by glomerular filtration rate and, more recently, using further categorization depending on the level of glomerular filtration rate and albuminuria by the Kidney Disease Improving Global Outcomes initiative. Registered dietitian nutritionists can be reimbursed for medical nutrition therapy in chronic kidney disease stages 3 to 4 for specific clients under Center for Medicare and Medicaid Services coverage. This predialysis medical nutrition therapy counseling has been shown to both potentially delay progression to stage 5 (renal replacement therapy) and decrease first-year mortality after initiation of hemodialysis. The Joint Standards Task Force of the American Dietetic Association (now the Academy of Nutrition and Dietetics), the Renal Nutrition Dietetic Practice Group, and the National Kidney Foundation Council on Renal Nutrition collaboratively published 2009 Standards of Practice and Standards of Professional Performance for generalist, specialty, and advanced practice registered dietitian nutritionists in nephrology care. The purpose of this article is to provide an update on current recommendations for screening, diagnosis, and treatment of adults with chronic kidney disease for application in clinical practice for the generalist registered dietitian nutritionist using the evidence-based library of the Academy of Nutrition and Dietetics, published clinical practice guidelines (ie, National Kidney Foundation Council on Renal Nutrition, Renal Nutrition Dietetic Practice Group, Kidney Disease Outcomes Quality Initiative, and Kidney Disease Improving Global Outcomes), the Nutrition Care Process model, and peer-reviewed literature. Copyright © 2014 Academy of Nutrition and Dietetics. Published by Elsevier Inc. All rights reserved.

The Cache County Study on Memory in Aging: Factors Affecting Risk of Alzheimer's disease and its Progression after Onset

PubMed Central

Tschanz, JoAnn T.; Norton, Maria C.; Zandi, Peter P.; Lyketsos, Constantine G.

2014-01-01

The Cache County Study on Memory in Aging is a longitudinal, population-based study of Alzheimer's disease (AD) and other dementias. Initiated in 1995 and extending to 2013, the study has followed over 5,000 elderly residents of Cache County, Utah (USA) for over twelve years. Achieving a 90% participation rate at enrollment, and spawning two ancillary projects, the study has contributed to the literature on genetic, psychosocial and environmental risk factors for AD, late life cognitive decline, and the clinical progression of dementia after its onset. This paper describes the major study contributions to the literature on AD and dementia. PMID:24423221

The Cache County Study on Memory in Aging: factors affecting risk of Alzheimer's disease and its progression after onset.

PubMed

Tschanz, Joann T; Norton, Maria C; Zandi, Peter P; Lyketsos, Constantine G

2013-12-01

The Cache County Study on Memory in Aging is a longitudinal, population-based study of Alzheimer's disease (AD) and other dementias. Initiated in 1995 and extending to 2013, the study has followed over 5,000 elderly residents of Cache County, Utah (USA) for over twelve years. Achieving a 90% participation rate at enrolment, and spawning two ancillary projects, the study has contributed to the literature on genetic, psychosocial and environmental risk factors for AD, late-life cognitive decline, and the clinical progression of dementia after its onset. This paper describes the major study contributions to the literature on AD and dementia.

Post-marketing surveillance of Norplant((R)) contraceptive implants: II. Non-reproductive health(1).

PubMed

2001-04-01

This controlled cohort study aimed to evaluate the safety and efficacy of Norplant contraceptive implants in developing countries. Women initiating Norplant implants were index subjects and women initiating intrauterine devices (IUDs) or surgical sterilization were controls. Consenting participants at 32 clinics in eight developing countries were admitted and followed-up every 6 months for 5 years. Major and less serious health events during follow-up were recorded. Incidence rate ratios of health events adjusted for clinic were estimated for initial and current method use. This paper reports non-reproductive health events. The study involved 7,977 women initiating use of Norplant, 6,625 of IUD, and 1,419 of sterilization. Five years follow-up was completed for 94.6% of the women. The study accumulated 78,323 woman-years of observation. The initial method chosen accounted for 84.4% or more of observed woman-years in users of Norplant, IUD, or sterilization. Twenty-two of the recorded 34 deaths were due to accidents, suicide or homicide. Few deaths or major health events were due to cancer or acute cardiovascular diseases and were not associated with the contraceptive method used. The incidence rates of major health events were low and with two exceptions, there was no significant excess risk of serious morbidity for Norplant users compared with controls; among Norplant initiators gallbladder disease occurred at an incidence rate of 1.5 per 1,000 woman-years and was weakly associated with use of Norplant (rate ratio 1.52 [95% C.I. 1.02, 2.27]). For current Norplant users compared to controls, the rate ratio of a combined variable of hypertension and borderline hypertension was significantly elevated (1.81, [1.12, 2.92]). The occurrence of less serious health events was also low and several of them were significantly more often reported among Norplant users. Headache-migraine, weight gain, mood disturbances, pruritus, eczema, and acne had incidence rates among Norplant users of 11.5, 4.5, 2.8, 1.5, 1.4, and 0.9 per 1,000 woman-years, respectively, and were significantly higher than in controls. Respiratory health problems, nonspecific symptoms, and several ill-defined conditions were also significantly more often reported for Norplant users, but some of the excess incidence may be attributable to reporting and detection bias. The study confirms the safety with respect to serious disease of Norplant, IUDs, and sterilization.

School-Based Study of Complex Environmental Exposures and Related Health Effects in Children: Part A - Exposure. Final Report and Executive Summary.

ERIC Educational Resources Information Center

Minnesota Univ., Minneapolis. School of Public Health.

The School Health Initiative: Environment, Learning, and Disease (SHIELD) study examined children's exposure to complex mixtures of environmental agents (i.e., volatile organic chemicals, environmental tobacco smoke, allergens, bioaerosols, metals, and pesticides). Environmental, personal, and biological data were collected on ethnically and…

76 FR 27649 - Disease, Disability, and Injury Prevention and Control Special Interest Projects (SIPs): Initial...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-05-12

... Disadvantaged Communities, SIP11-041, Feasibility Study to Link Data from the National Breast and Cervical..., Management Analysis and Services Office, CDC, pursuant to Public Law 92-463. Matters To Be Discussed: The... Promote Colorectal Cancer Screening in Disadvantaged Communities, SIP11-041, Feasibility Study to Link...

78 FR 24220 - Submission for OMB Review; 30-Day Comment Request: Women's Health Initiative Observational Study

Federal Register 2010, 2011, 2012, 2013, 2014

2013-04-24

... of Section 3507(a)(1)(D) of the Paperwork Reduction Act of 1995, the National Heart, Lung, and Blood... Observational Study. Revision--OMB No. 0925-0414, Expiration Date: 07/31/2013. National Heart, Lung, and Blood... women, namely, coronary heart disease, breast and [[Page 24221

Sticker charts: a method for improving adherence to treatment of chronic diseases in children.

PubMed

Luersen, Kara; Davis, Scott A; Kaplan, Sebastian G; Abel, Troy D; Winchester, Woodrow W; Feldman, Steven R

2012-01-01

Poor adherence is a common problem and may be an underlying cause of poor clinical outcomes. In pediatric populations, positive reinforcement techniques such as sticker charts may increase motivation to adhere to treatment regimens. To review the use of sticker charts to improve adherence in children with chronic disease, Medline and PsycINFO searches were conducted using the key words "positive reinforcement OR behavior therapy" and "adherence OR patient compliance" and "child." Randomized controlled retrospective cohort or single-subject-design studies were selected. Studies reporting adherence to the medical treatment of chronic disease in children using positive reinforcement techniques were included in the analysis. The systematic search was supplemented by identifying additional studies identified through the reference lists and authors of the initial articles found. Positive reinforcement techniques such as sticker charts increase adherence to medical treatment regimens. In several studies, this effect was maintained for months after the initial intervention. Better adherence correlated with better clinical outcomes in some, but not all, studies. Few studies examining the use of sticker charts were identified. Although single-subject-design studies are useful in establishing the effect of a behavioral intervention, larger randomized controlled trials would help determine the precise efficacy of sticker chart interventions. Adherence to medical treatments in children can be increased using sticker charts or other positive reinforcement techniques. This may be an effective means to encourage children with atopic dermatitis to apply their medications and improve clinical outcomes. © 2012 Wiley Periodicals, Inc.

Mood changes following social dance sessions in people with Parkinson's disease.

PubMed

Lewis, Carine; Annett, Lucy E; Davenport, Sally; Hall, Amelia A; Lovatt, Peter

2016-04-01

Dance interventions have physical benefits for the elderly, especially those with Parkinson's disease. This study assessed the psychological benefits of dance. A total of 37 participants, with either Parkinson's disease (n= 22) or age-matched controls (n= 15) completed mood questionnaires before and after a 10-week dance intervention. An overall reduction in total mood disturbance and a specific reduction in anger were observed. In addition, less fatigue was found for those initially scoring higher in depression. This suggests that dance can provide psychological benefits for both people with Parkinson's disease and the elderly, with findings suggesting that this is an avenue to be explored further. © The Author(s) 2014.

Is intestinal inflammation linking dysbiosis to gut barrier dysfunction during liver disease?

PubMed Central

Brandl, Katharina

2016-01-01

Changes in the intestinal microbiota composition contribute to the pathogenesis of many disorders including gastrointestinal and liver diseases. Recent studies have broadened our understanding of the “gut-liver” axis. Dietary changes, other environmental and genetic factors can lead to alterations in the microbiota. Dysbiosis can further disrupt the integrity of the intestinal barrier leading to pathological bacterial translocation and the initiation of an inflammatory response in the liver. In this article, the authors dissect the different steps involved in disease pathogenesis to further refine approaches for the medical management of liver diseases. The authors will specifically discuss the role of dysbiosis in inducing intestinal inflammation and increasing intestinal permeability. PMID:26088524

Lipids, inflammation, and chronic kidney disease: a SHARP perspective.

PubMed

Waters, David D; Vogt, Liffert

2018-04-01

Accumulating evidence indicates that inflammation plays a role in the initiation and progression of chronic kidney disease. In the Study of Heart and Renal Protection (SHARP) trial, higher baseline C-reactive protein and higher baseline low-density lipoprotein cholesterol levels were both associated with a higher risk of cardiovascular events, but higher baseline C-reactive protein levels were also associated with a higher risk of nonvascular events. Simvastatin/ezetimibe reduced cardiovascular events independent of baseline C-reactive protein levels. However, this observation does not exclude inflammation as a causal factor for cardiovascular disease development in chronic kidney disease patients. Copyright © 2018 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

Osteoarthritis as a disease of the cartilage pericellular matrix.

PubMed

Guilak, Farshid; Nims, Robert; Dicks, Amanda; Wu, Chia-Lung; Meulenbelt, Ingrid

2018-05-22

Osteoarthritis is a painful joint disease characterized by progressive degeneration of the articular cartilage as well as associated changes to the subchondral bone, synovium, and surrounding joint tissues. While the effects of osteoarthritis on the cartilage extracellular matrix (ECM) have been well recognized, it is now becoming apparent that in many cases, the onset of the disease may be initially reflected in the matrix region immediately surrounding the chondrocytes, termed the pericellular matrix (PCM). Growing evidence suggests that the PCM - which along with the enclosed chondrocytes are termed the "chondron" - acts as a critical transducer or "filter" of biochemical and biomechanical signals for the chondrocyte, serving to help regulate the homeostatic balance of chondrocyte metabolic activity in response to environmental signals. Indeed, it appears that alterations in PCM properties and cell-matrix interactions, secondary to genetic, epigenetic, metabolic, or biomechanical stimuli, could in fact serve as initiating or progressive factors for osteoarthritis. Here, we discuss recent advances in the understanding of the role of the PCM, with an emphasis on the reciprocity of changes that occur in this matrix region with disease, as well as how alterations in PCM properties could serve as a driver of ECM-based diseases such as osteoarthritis. Further study of the structure, function, and composition of the PCM in normal and diseased conditions may provide new insights into the understanding of the pathogenesis of osteoarthritis, and presumably new therapeutic approaches for this disease. Copyright © 2017. Published by Elsevier B.V.

Genetic insights into age-related macular degeneration: Controversies addressing Risk, Causality, and Therapeutics

PubMed Central

Gorin, Michael B.

2012-01-01

Age-related macular degeneration (AMD) is a common condition among the elderly population that leads to the progressive central vision loss and serious compromise of quality of life for its sufferers. It is also one of the few disorders for whom the investigation of its genetics has yielded rich insights into its diversity and causality and holds the promise of enabling clinicians to provide better risk assessments for individuals as well as to develop and selectively deploy new therapeutics to either prevent or slow the development of disease and lessen the threat of vision loss. The genetics of AMD began initially with the appreciation of familial aggregation and increase risk and expanded with the initial association of APOE variants with the disease. The first major breakthroughs came with family-based linkage studies of affected (and discordant) sibs, which identified a number of genetic loci and led to the targeted search of the 1q31 and 10q26 loci for associated variants. Three of the initial four reports for the CFH variant, Y402H, were based on regional candidate searches, as were the two initial reports of the ARMS2/HTRA1 locus variants. Case-control association studies initially also played a role in discovering the major genetic variants for AMD, and the success of those early studies have been used to fuel enthusiasm for the methodology for a number of diseases. Until 2010, all of the subsequent genetic variants associated with AMD came from candidate gene testing based on the complement factor pathway. In 2010, several large-scale genome-wide association studies (GWAS) identified genes that had not been previously identified. Much of this historical information is available in a number of recent reviews.(Chen et al., 2010b; Deangelis et al., 2011; Fafowora and Gorin, 2012b; Francis and Klein, 2011; Kokotas et al., 2011) Large meta analysis of AMD GWAS has added new loci and variants to this collection.(Chen et al., 2010a; Kopplin et al., 2010; Yu et al., 2011) This paper will focus on the ongoing controversies that are confronting AMD genetics at this time, rather than attempting to summarize this field, which has exploded in the past 5 years. PMID:22561651

A technique to screen American beech for resistance to the beech scale insect (Cryptococcus fagisuga Lind.)

Treesearch

Jennifer L. Koch; David W. Carey

2014-01-01

Beech bark disease (BBD) results in high levels of initial mortality, leaving behind survivor trees that are greatly weakened and deformed. The disease is initiated by feeding activities of the invasive beech scale insect, Cryptococcus fagisuga, which creates entry points for infection by one of the Neonectria species of fungus....

Update on Outcome Measure Development for Large Vessel Vasculitis: Report from OMERACT 12

PubMed Central

Aydin, Sibel Zehra; Direskeneli, Haner; Sreih, Antoine; Alibaz-Oner, Fatma; Gul, Ahmet; Kamali, Sevil; Hatemi, Gulen; Kermani, Tanaz; Mackie, Sarah L.; Mahr, Alfred; Meara, Alexa; Milman, Nataliya; Nugent, Heidi; Robson, Joanna; Tomasson, Gunnar; Merkel, Peter A.

2015-01-01

Objective The rarity of large vessel vasculitis (LVV) is a major factor limiting randomized controlled trials in LVV, resulting in treatment choices in these diseases that are guided mainly by observational studies and expert opinion. Further complicating trials in LVV is the absence of validated and meaningful outcome measures. The Outcome Measures in Rheumatology (OMERACT) vasculitis working group initiated the Large Vessel Vasculitis task force in 2009 to develop data-driven, validated outcome tools for clinical investigation in LVV. This report summarizes the progress that has been made on a disease activity assessment tool and patient-reported outcomes in LVV as well as the group’s research agenda. Methods The OMERACT LVV task force brought an international group of investigators and patient research partners together to work collaboratively on developing outcome tools. The group initially focused on disease activity assessment tools in LVV. Following a systematic literature review, an international Delphi exercise was conducted to obtain expert opinion on principles and domains for disease assessment. The OMERACT vasculitis working group’s LVV task force is also conducting qualitative research with patients, including interviews, focus groups, and engaging patients as research partners, all to ensure that the approach to disease assessment includes measures of patients’ perspectives and that patients have input into the research agenda and process. Results The preliminary results of both the Delphi exercise and the qualitative interviews were discussed at the OMERACT 12 (2014) meeting and the completion of the analyses will produce an initial set of domains and instruments to form the basis of next steps in the research agenda. Conclusion The research agenda continues to evolve, with the ultimate goal of developing an OMERACT-endorsed core set of outcome measures for use in clinical trials of LVV. PMID:26077399

99mTc-stannous colloid white cell scintigraphy in childhood inflammatory bowel disease.

PubMed

Peacock, Kenneth; Porn, Ute; Howman-Giles, Robert; O'Loughlin, Edward; Uren, Roger; Gaskin, Kevin; Dorney, Stuart; Kamath, Ramanand

2004-02-01

99mTc-Labeled white cell scintigraphy (WCS) has been used for the investigation of inflammatory bowel disease (IBD) in adults, but data on children are limited. The most common agent used is (99m) Tc-hexamethylpropyleneamine oxime (HMPAO); however, this agent has limitations. In a retrospective study, we assessed the use of (99m)Tc-stannous colloid WCS for the initial evaluation of children with suspected IBD. Diagnostic, endoscopic, and contrast radiography results were retrospectively collected from the medical records. Two experienced nuclear physicians unaware of the patient data interpreted the WCS results, with agreement reached by consensus. Statistical analysis was performed on the ability of WCS to detect active disease and localize it topographically and on a comparison of diagnostic methods, using a combination of clinical features and endoscopy as the reference standard. Between 1996 and 1999, 64 patients (35 male and 29 female; mean age, 12.5 y; age range, 2-19 y) had WCS performed, with IBD subsequently diagnosed in 34 patients. (99m)Tc-Stannous colloid WCS had an 88% sensitivity, 90% specificity, and 8.8 likelihood ratio for initial investigation of IBD. Agreement was poor for topographic localization of disease. Small-bowel series had a 75% sensitivity, 50% specificity, and 1.5 likelihood ratio for detecting endoscopic disease of the terminal ileum and proximal colon. Our results confirm that WCS is a useful imaging technique for the initial evaluation of patients with suspected IBD. (99m)Tc-Stannous colloid had results at least comparable to those of other WCS agents, and in children, (99m)Tc-stannous colloid WCS should be preferred in view of lower cost, shorter preparation time, and the smaller blood volumes required.

New Beginnings in Alzheimer's Disease: The Most Prevalent Tauopathy.

PubMed

Hernández, Félix; Llorens-Martín, María; Bolós, Marta; Pérez, Mar; Cuadros, Raquel; Pallas-Bazarra, Noemí; Zabala, Juan C; Avila, Jesús

2018-01-01

Alzheimer's disease (AD) is characterized by the presence of two aberrant structures: namely senile plaques, composed of amyloid-β peptide (Aβ), and neurofibrillary tangles, composed of tau protein. In this regard, Aβ and tau protein have been widely studied in research efforts aiming to find a therapy for AD. Aβ and tau pathologies do not always overlap. The precursor of Aβ is expressed in peripheral tissues and in the central nervous system (CNS), whereas tau is mainly a neuronal protein. Since AD is a disease of the CNS, it has been proposed that Aβ may initiate the disease process, with tau being the executor. In this review, we will focus on future studies of tau pathology, although we will comment on new beginnings for AD, as other molecules other than Aβ and tau may be involved in the onset of dementia.

The Social Determinants of Chronic Disease

PubMed Central

Cockerham, William C.; Hamby, Bryant W.; Oates, Gabriela R.

2017-01-01

This review article addresses the concept of the social determinants of health (SDH), selected theories, and its application in studies of chronic disease. Once ignored or regarded only as distant or secondary influences on health and disease, social determinants have been increasingly acknowledged as fundamental causes of health afflictions. For the purposes of this discussion, SDH refers to SDH variables directly relevant to chronic diseases and, in some circumstances, obesity, in the research agenda of the Mid-South Transdisciplinary Collaborative Center for Health Disparities Research. The health effects of SDH are initially discussed with respect to smoking and the social gradient in mortality. Next, four leading SDH theories—life course, fundamental cause, social capital, and health lifestyle theory—are reviewed with supporting studies. The article concludes with an examination of neighborhood disadvantage, social networks, and perceived discrimination in SDH research. PMID:27989293

Disturbance Driven Colony Fragmentation as a Driver of a Coral Disease Outbreak

PubMed Central

Brandt, Marilyn E.; Smith, Tyler B.; Correa, Adrienne M. S.; Vega-Thurber, Rebecca

2013-01-01

In September of 2010, Brewer's Bay reef, located in St. Thomas (U.S. Virgin Islands), was simultaneously affected by abnormally high temperatures and the passage of a hurricane that resulted in the mass bleaching and fragmentation of its coral community. An outbreak of a rapid tissue loss disease among coral colonies was associated with these two disturbances. Gross lesion signs and lesion progression rates indicated that the disease was most similar to the Caribbean coral disease white plague type 1. Experiments indicated that the disease was transmissible through direct contact between colonies, and five-meter radial transects showed a clustered spatial distribution of disease, with diseased colonies being concentrated within the first meter of other diseased colonies. Disease prevalence and the extent to which colonies were bleached were both significantly higher on unattached colony fragments than on attached colonies, and disease occurred primarily on fragments found in direct contact with sediment. In contrast to other recent studies, disease presence was not related to the extent of bleaching on colonies. The results of this study suggest that colony fragmentation and contact with sediment played primary roles in the initial appearance of disease, but that the disease was capable of spreading among colonies, which suggests secondary transmission is possible through some other, unidentified mechanism. PMID:23437335

Locoregional disease patterns in well-differentiated and dedifferentiated retroperitoneal liposarcoma: implications for the extent of resection?

PubMed

Tseng, William W; Madewell, John E; Wei, Wei; Somaiah, Neeta; Lazar, Alexander J; Ghadimi, Markus P; Hoffman, Aviad; Pisters, Peter W T; Lev, Dina C; Pollock, Raphael E

2014-07-01

Well-differentiated (WD)/dedifferentiated (DD) liposarcoma is the most common soft tissue sarcoma of the retroperitoneum. The frequency of distant metastasis is low and the major burden of disease is locoregional. We sought to define the patterns of locoregional disease to help guide surgical decision making. Data were collected from 247 patients with de novo or recurrent tumors treated at our institution from 1993 to early 2012. The number and location of tumors at both initial presentation and subsequent locoregional recurrence were determined by combined analysis of operative dictations and radiologic imaging. Thirty-four percent of patients had multifocal locoregional disease (two or more tumors) at initial presentation to our institution, including 9 % who had tumors at synchronous remote retroperitoneal sites. The impact of multifocal disease on overall survival was dependent on histologic subtype (WD vs. DD) and disease presentation (de novo vs. recurrence) at the time of resection. Among patients with initial unifocal disease, 57 % progressed to multifocal locoregional disease with subsequent recurrence, including 11 % with new tumors outside of the original resection field. No clinicopathologic or treatment-related variable, including the type or extent of resection, was predictive of either multifocal or 'outside field' progression. Multifocal disease is common in patients with WD/DD retroperitoneal liposarcoma, and tumors can also develop at remote, locoregional sites. Surgical resection remains the primary method of locoregional control in this disease; however, the aggressiveness of resection should be individualized, with consideration of both tumor and patient-related factors.

Patient initiated clinics for patients with chronic or recurrent conditions managed in secondary care: a systematic review of patient reported outcomes and patient and clinician satisfaction

PubMed Central

2013-01-01

Background The cost to the NHS of missed or inappropriate hospital appointments is considerable. Alternative methods of appointment scheduling might be more flexible to patients’ needs without jeopardising health and service quality. The objective was to systematically review evidence of patient initiated clinics in secondary care on patient reported outcomes among patients with chronic/recurrent conditions. Methods Seven databases were searched from inception to June 2013. Hand searching of included studies references was also conducted. Studies comparing the effects of patient initiated clinics with traditional consultant led clinics in secondary care for patients with long term chronic or recurrent diseases on health related quality of life and/or patient satisfaction were included. Data was extracted by one reviewer and checked by a second. Results were synthesised narratively. Results Seven studies were included in the review, these covered a total of 1,655 participants across three conditions: breast cancer, inflammatory bowel disease and rheumatoid arthritis. Quality of reporting was variable. Results showed no significant differences between the intervention and control groups for psychological and health related quality of life outcomes indicating no evidence of harm. Some patients reported significantly more satisfaction using patient-initiated clinics than usual care (p < 0.001). Conclusions The results show potential for patient initiated clinics to result in greater patient and clinician satisfaction. The patient-consultant relationship appeared to play an important part in patient satisfaction and should be considered an important area of future research as should the presence or absence of a guidebook to aid self-management. Patient initiated clinics fit the models of care suggested by policy makers and so further research into long term outcomes for patients and service use in this area of practice is both relevant and timely. PMID:24289832

Cardiac consequences of diabetes mellitus.

PubMed

Shehadeh, A; Regan, T J

1995-06-01

A variety of disciplines including noninvasive and invasive cardiac methodologies, as well as epidemiologic studies, have provided information that has altered our view on the relation of diabetes to cardiac disease. Instead of an exclusive focus on coronary artery disease, it is now recognized that heart muscle can be independently involved in diabetic patients. In diabetics without known cardiac disease, abnormalities of left ventricular mechanical function have been demonstrated in 40 to 50% of subjects, and it is primarily a diastolic phenomenon. Left ventricular hypertrophy may eventually appear in the absence of hypertension. The diastolic dysfunction appears related to interstitial collagen deposition, largely attributable to diminished degradation. The presence of even moderate obesity intensifies the abnormality. Reversibility of this process is not readily achieved with chronic insulin therapy. Experimental studies have indicated normalization of the collagen alteration by endurance training, begun relatively early in the disease process. General measures of management include the control of other cardiac risk factors and a reasonable program of physical activity. The high mortality during an initial acute myocardial infarction has been attributed to heart failure, which is managed as in nondiabetic patients. Recently, the early introduction of aspirin, thrombolysis, and beta-adrenergic blockade has reduced mortality during the initial infarction. Chronic use of the latter agent over the subsequent years has also proven to be more beneficial in diabetic patients with acute myocardial infarction compared with nondiabetic patients.

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.

Vasculitic central retinal vein occlusion: The presenting sign of seronegative rheumatoid arthritis.

PubMed

Trese, Matthew G J; Yonekawa, Yoshihiro; Thomas, Benjamin J; Randhawa, Sandeep

2016-07-01

To report the case of a patient who presented with a vasculitic central retinal vein occlusion (CRVO), which was the result of an undiagnosed systemic inflammatory condition, seronegative rheumatoid arthritis (RA). The patient presented with reduced vision in the left eye and polyarthralgia. Fundoscopic examination revealed a central retinal vein occlusion (CRVO) with concurrent evidence of vasculitis. Work-up for polyarthralgia included comprehensive serologic testing for connective tissue disease, including Vectra ® disease activity (DA) testing. Results of these studies confirmed the diagnosis of seronegative rheumatoid arthritis (RA). Systemic steroid therapy was initiated with subsequent anatomic and visual improvement. We hypothesize that the systemic inflammation-a hallmark of RA-led to the development of a vasculitic CRVO and, thus, the retinal manifestations served as the disease marker that prompted thorough work-up of the patient's disease, even in the face of initial seronegativity. This case serves as a reminder that, in the setting of CRVO and polyarthralgia, systemic inflammatory conditions must be considered as the underlying etiology. Further, this case report highlights our evolving understanding of the role that serologic markers play in the diagnosis and monitoring of RA.

Mouse xenograft modeling of human adult acute lymphoblastic leukemia provides mechanistic insights into adult LIC biology

PubMed Central

Dey, Aditi; Castleton, Anna Z.; Schwab, Claire; Samuel, Edward; Sivakumaran, Janani; Beaton, Brendan; Zareian, Nahid; Zhang, Christie Yu; Rai, Lena; Enver, Tariq; Moorman, Anthony V.; Fielding, Adele K.

2014-01-01

The distinct nature of acute lymphoblastic leukemia (ALL) in adults, evidenced by inferior treatment outcome and different genetic landscape, mandates specific studies of disease-initiating mechanisms. In this study, we used NOD/LtSz-scid IL2Rγ nullc (NSG) mouse xenotransplantation approaches to elucidate leukemia-initiating cell (LIC) biology in primary adult precursor B (pre-B) ALL to optimize disease modeling. In contrast with xenografting studies of pediatric ALL, we found that modification of the NSG host environment using preconditioning total body irradiation (TBI) was indispensable for efficient engraftment of adult non-t(4;11) pre-B ALL, whereas t(4;11) pre-B ALL was successfully reconstituted without this adaptation. Furthermore, TBI-based xenotransplantation of non-t(4;11) pre-B ALL enabled detection of a high frequency of LICs (<1:6900) and permitted frank leukemic engraftment from a remission sample containing drug-resistant minimal residual disease. Investigation of TBI-sensitive stromal-derived factor-1/chemokine receptor type 4 signaling revealed greater functional dependence of non-t(4;11) pre-B ALL on this niche-based interaction, providing a possible basis for the differential engraftment behavior. Thus, our studies establish the optimal conditions for experimental modeling of human adult pre-B ALL and demonstrate the critical protumorogenic role of microenvironment-derived SDF-1 in regulating adult pre-B LIC activity that may present a therapeutic opportunity. PMID:24825861

Agreement between the results of meta-analyses from case reports and from clinical studies regarding the efficacy of laronidase therapy in patients with mucopolysaccharidosis type I who initiated enzyme replacement therapy in adult age: An example of case reports meta-analyses as an useful tool for evidence-based medicine in rare diseases.

PubMed

Sampayo-Cordero, Miguel; Miguel-Huguet, Bernat; Pardo-Mateos, Almudena; Moltó-Abad, Marc; Muñoz-Delgado, Cecilia; Pérez-López, Jordi

2018-02-01

Case reports might have a prominent role in the rare diseases field, due to the small number of patients affected by one such disease. A previous systematic review regarding the efficacy of laronidase therapy in patients with mucopolysaccharidosis type I (MPS-I) who initiated enzyme replacement therapy (ERT) in adult age has been published. The review included a meta-analysis of 19 clinical studies and the description of eleven case reports. It was of interest to perform a meta-analysis of those case reports to explore the role of such meta-analyses as a tool for evidence-based medicine in rare diseases. The study included all case reports with standard treatment regimen. Primary analysis was the percentage of case reports showing an improvement in a specific outcome. Only when that percentage was statistically higher than 5%, the improvement was confirmed as such. The outcomes that accomplished this criterion were ranked and compared to the GRADE criteria obtained by those same outcomes in the previous meta-analysis of clinical studies. There were three outcomes that had a significant improvement: Urine glycosaminoglycans, liver volume and 6-minute walking test. Positive and negative predictive values, sensitivity and specificity for the results of the meta-analysis of case reports as compared to that of clinical studies were 100%, 88.9%, 75% and 100%, respectively. Accordingly, absolute (Rho=0.82, 95%CI: 0.47 to 0.95) and relative agreement (Kappa=0.79, 95%CI: 0.593 to 0.99) between the number of case reports with improvement in a specific outcome and the GRADE evidence score for that outcome were good. Sensitivity analysis showed that agreement between the meta-analysis of case reports and that of the clinical studies were good only when using a strong confirmatory strategy for outcome improvement in case reports. We found an agreement between the results of meta-analyses from case reports and from clinical studies in the efficacy of laronidase therapy in patients with MPS-I who initiated ERT in adult age. This agreement suggests that combining case reports quantitatively, rather than analyzing them separately or qualitatively, may improve conclusions in the field of rare diseases. Copyright © 2018 Elsevier Inc. All rights reserved.

76 FR 24897 - National Institute of Diabetes And Digestive and Kidney Diseases; Notice of Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2011-05-03

... Diabetes And Digestive and Kidney Diseases; Notice of Meeting Pursuant to section 10(d) of the Federal... Digestive and Kidney Diseases Initial Review Group, Kidney, Urologic and Hematologic Diseases D Subcommittee..., Endocrinology and Metabolic Research; 93.848, Digestive Diseases and Nutrition Research; 93.849, Kidney Diseases...

78 FR 58322 - National Institute of Diabetes and Digestive and Kidney Diseases; Notice of Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2013-09-23

... Diabetes and Digestive and Kidney Diseases; Notice of Meeting Pursuant to section 10(d) of the Federal... Digestive and Kidney Diseases Initial Review Group, Digestive Diseases and Nutrition C Subcommittee. Date...; 93.848, Digestive Diseases and Nutrition Research; 93.849, Kidney Diseases, Urology and Hematology...

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

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.

Exploring the cause of initially reactive bovine brains on rapid tests for BSE

PubMed Central

Dudas, Sandor; James, Jace; Anderson, Renee; Czub, Stefanie

2015-01-01

ABSTRACT Bovine spongiform encephalopathy (BSE) is an invariably fatal prion disease of cattle. The identification of the zoonotic potential of BSE prompted safety officials to initiate surveillance testing for this disease. In Canada, BSE surveillance is primarily focused on high risk cattle including animals which are dead, down and unable to rise, diseased or distressed. This targeted surveillance results in the submission of brain samples with a wide range of tissue autolysis and associated contaminants. These contaminants have the potential to interfere with important steps of surveillance tests resulting in initially positive test results requiring additional testing to confirm the disease status of the animal. The current tests used for BSE screening in Canada utilize the relative protease resistance of the prion protein gained when it misfolds from PrPC to PrPSc as part of the disease process. Proteinase K completely digests PrPC in normal brains, but leaves most of the PrPSc in BSE positive brains intact which is detected using anti-prion antibodies. These tests are highly reliable but occasionally give rise to initially reactive/false positive results. Test results for these reactive samples were close to the positive/negative cut-off on a sub set of test platforms. This is in contrast to all of the previous Canadian positive samples whose numeric values on these same test platforms were 10 to 100 fold greater than the test positive/negative cut-off. Here we explore the potential reason why a sample is repeatedly positive on a sub-set of rapid surveillance tests, but negative on other test platforms. In order to better understand and identify what might cause these initial reactions, we have conducted a variety of rapid and confirmatory assays as well as bacterial isolation and identification on BSE positive, negative and initially reactive samples. We observed high levels of viable bacterial contamination in initially reactive samples suggesting that the reactivity may be related to bacterial factors. Several bacteria isolated from the initially reactive samples have characteristics of biofilm forming bacteria and this extracellular matrix might play a role in preventing complete digestion of PrPC in these samples. PMID:26689488

Skeletal involvement in Gaucher disease: An observational multicenter study of prognostic factors in the Argentine Gaucher disease patients.

PubMed

Drelichman, Guillermo; Fernández Escobar, Nicolás; Basack, Nora; Aversa, Luis; Larroude, María Silvia; Aguilar, Gabriela; Szlago, Marina; Schenone, Andrea; Fynn, Alcyra; Cuello, María Fernanda; Aznar, Marcela; Fernández, Ramiro; Ruiz, Alba; Reichel, Paola; Guelbert, Norberto; Robledo, Hugo; Watman, Nora; Bolesina, Moira; Elena, Graciela; Veber, S Ernesto; Pujal, Graciela; Galván, Graciela; Chain, Juan José; Arizo, Adriana; Bietti, Julieta; Bar, Daniel; Dragosky, Marta; Marquez, Marisa; Feldman, Leonardo; Muller, Katja; Zirone, Sandra; Buchovsky, Greogorio; Lanza, Victoria; Sanabria, Alba; Fernández, Ignacio; Jaureguiberry, Rossana; Contte, Marcelo; Barbieri María, Angie; Maro, Alejandra; Zárate, Graciela; Fernández, Gabriel; Rapetti, María Cristina; Donato, Hugo; Degano, Adriana; Kantor, Gustavo; Albina, Roberto; Á Lvarez Bollea, María; Brun, María; Bacciedoni, Viviana; Del Río, Francis; Soberón, Bárbara; Boido, Nazario; Schweri, Maya; Borchichi, Sandra; Welsh, Victoria; Corrales, Marcela; Cedola, Alejandra; Carvani, Analía; Diez, Blanca; Richard, Lucía; Baduel, Ccecilia; Nuñez, Gabriela; Colimodio, Rubén; Barazzutti, Lucía; Medici, Hugo; Meschengieser, Susana; Damiani, Germán; Nucifora, María; Girardi, Beatriz; Gómez, Sergio; Papucci, Maura; Verón, David; Quiroga, Luis; Carro, Gustavo; De Ambrosio, Patricia; Ferro, José; Pujol, Marcelo; Castella, Cristina Cabral; Franco, Liliana; Nisnovich, Gisela; Veloso, María; Pacheco, Isabel; Savarino, Mario; Marino, Andrés; Saavedra, José Luis

2016-10-01

Patients with Gaucher type 1 (GD1) throughout Argentina were enrolled in the Argentine bone project to evaluate bone disease and its determinants. We focused on presence and predictors of bone lesions (BL) and their relationship to therapeutic goals (TG) with timing and dose of enzyme replacement therapy (ERT). A total of 124 patients on ERT were enrolled in a multi-center study. All six TG were achieved by 82% of patients: 70.1% for bone pain and 91.1% for bone crisis. However, despite the fact that bone TGs were achieved, residual bone disease was present in 108 patients on ERT (87%) at time 0. 16% of patients showed new irreversible BL (bone infarcts and avascular osteonecrosis) despite ERT, suggesting that they appeared during ERT or were not detected at the moment of diagnosis. We observed 5 prognostic factors that predicted a higher probability of being free of bone disease: optimal ERT compliance; early diagnosis; timely initiation of therapy; ERT initiation dose ≥45 UI/kg/EOW; and the absence of history of splenectomy. Skeletal involvement was classified into 4 major phenotypic groups according to BL: group 1 (12.9%) without BL; group 2 (28.2%) with reversible BL; group 3 (41.9%) with reversible BL and irreversible chronic BL; and group 4 (16.9%) with acute irreversible BL. Our study identifies prognostic factors for achieving best therapeutic outcomes, introduces new risk stratification for patients and suggests the need for a redefinition of bone TG. Am. J. Hematol. 91:E448-E453, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

An approach for estimating item sensitivity to within-person change over time: An illustration using the Alzheimer's Disease Assessment Scale-Cognitive subscale (ADAS-Cog).

PubMed

Dowling, N Maritza; Bolt, Daniel M; Deng, Sien

2016-12-01

When assessments are primarily used to measure change over time, it is important to evaluate items according to their sensitivity to change, specifically. Items that demonstrate good sensitivity to between-person differences at baseline may not show good sensitivity to change over time, and vice versa. In this study, we applied a longitudinal factor model of change to a widely used cognitive test designed to assess global cognitive status in dementia, and contrasted the relative sensitivity of items to change. Statistically nested models were estimated introducing distinct latent factors related to initial status differences between test-takers and within-person latent change across successive time points of measurement. Models were estimated using all available longitudinal item-level data from the Alzheimer's Disease Assessment Scale-Cognitive subscale, including participants representing the full-spectrum of disease status who were enrolled in the multisite Alzheimer's Disease Neuroimaging Initiative. Five of the 13 Alzheimer's Disease Assessment Scale-Cognitive items demonstrated noticeably higher loadings with respect to sensitivity to change. Attending to performance change on only these 5 items yielded a clearer picture of cognitive decline more consistent with theoretical expectations in comparison to the full 13-item scale. Items that show good psychometric properties in cross-sectional studies are not necessarily the best items at measuring change over time, such as cognitive decline. Applications of the methodological approach described and illustrated in this study can advance our understanding regarding the types of items that best detect fine-grained early pathological changes in cognition. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

Clinical significance of laryngopharyngeal reflux in patients with chronic obstructive pulmonary disease.

PubMed

Jung, Young Ho; Lee, Doh Young; Kim, Dong Wook; Park, Sung Soo; Heo, Eun Young; Chung, Hee Soon; Kim, Deog Kyeom

2015-01-01

Although chronic obstructive pulmonary disease (COPD) is closely associated with gastroesophageal reflux disease (GERD), the clinical significance of laryngopharyngeal reflux (LPR) is not fully understood in COPD. Prospective cohorts were established among 118 patients with COPD from March 2013 to July 2014. Thirty-two age-matched and sex-matched normal controls, who had routine health check-ups during the study period, were included. Laryngopharyngeal reflux finding scores (RFS) and reflux symptom index (RSI) for LPR were subjected to association analysis with severity and acute exacerbation of COPD during the 1-year follow-up. The mean age of patients enrolled in the study was 69.2±8.8 years, with 93.2% being male. Positive RFS (>7) and RSI (>13) were observed in 51 (42.5%) and six patients (5.0%), respectively. RFS and RSI were significantly higher in patients with COPD than in normal, healthy patients (P<0.001). RFS was significantly correlated with residual volume/total lung capacity (%, P=0.048). Scores for diffuse laryngeal edema, erythema, and hyperemia were significantly higher in the high-risk group (Global Initiative for Chronic Obstructive Lung Disease classification C and D; P=0.025 and P=0.049, respectively), while RSI was significantly higher in the more symptomatic group (Global Initiative for Chronic Obstructive Lung Disease classification B and D; P=0.047). RSI and RFS were significant predictors for severe acute exacerbation of COPD (P=0.03 and P=0.047, respectively), while only RSI was associated with severity of dyspnea. Laryngeal examination and evaluation of laryngeal reflux symptom could be a surrogate clinical indicator related to severe acute exacerbation of COPD. Further studies of LPR in COPD patients should be considered.

A complete categorization of multiscale models of infectious disease systems.

PubMed

Garira, Winston

2017-12-01

Modelling of infectious disease systems has entered a new era in which disease modellers are increasingly turning to multiscale modelling to extend traditional modelling frameworks into new application areas and to achieve higher levels of detail and accuracy in characterizing infectious disease systems. In this paper we present a categorization framework for categorizing multiscale models of infectious disease systems. The categorization framework consists of five integration frameworks and five criteria. We use the categorization framework to give a complete categorization of host-level immuno-epidemiological models (HL-IEMs). This categorization framework is also shown to be applicable in categorizing other types of multiscale models of infectious diseases beyond HL-IEMs through modifying the initial categorization framework presented in this study. Categorization of multiscale models of infectious disease systems in this way is useful in bringing some order to the discussion on the structure of these multiscale models.

Personality profile and affective state of patients with inflammatory bowel disease.

PubMed Central

Robertson, D A; Ray, J; Diamond, I; Edwards, J G

1989-01-01

The Eysenck Personality Inventory and Hospital Anxiety and Depression scale were administered to 80 patients undergoing medical treatment for long standing inflammatory bowel disease: 22 patients were studied before the diagnosis was established and 40 patients with diabetes mellitus served as controls. High neuroticism and introversion scores were more prevalent in the patients with inflammatory bowel disease than controls (p less than 0.05) and these characteristics were as prominent in patients before diagnosis as in established cases. Introversion scores increased with the duration of disease (r = 0.51). Depression was uncommon, occurring only in patients with active chronic disease. Patients believed there was a close link between personality, stress and disease activity. Fifty six of the patients recognised factors that initiated the disease and in 42 this was thought to be a stressful life event or a 'nervous personality'. PMID:2731754

75 FR 8975 - National Institute of Allergy and Infectious Diseases; Notice of Closed Meetings

Federal Register 2010, 2011, 2012, 2013, 2014

2010-02-26

... Committee: Microbiology, Infectious Diseases and AIDS Initial Review Group, Acquired Immunodeficiency...; 93.856, Microbiology and Infectious Diseases Research, National Institutes of Health, HHS) [[Page...

Peer support of complex health behaviors in prevention and disease management with special reference to diabetes: systematic reviews.

PubMed

Fisher, Edwin B; Boothroyd, Renée I; Elstad, Emily A; Hays, Laura; Henes, Amy; Maslow, Gary R; Velicer, Clayton

2017-01-01

Examine Peer Support (PS) for complex, sustained health behaviors in prevention or disease management with emphasis on diabetes prevention and management. PS was defined as emotional, motivational and practical assistance provided by nonprofessionals for complex health behaviors. Initial review examined 65 studies drawn from 1442 abstracts identified through PubMed, published 1/1/2000-7/15/2011. From this search, 24 reviews were also identified. Extension of the search in diabetes identified 30 studies published 1/1/2000-12/31/2015. In initial review, 54 of all 65 studies (83.1%) reported significant impacts of PS, 40 (61.5%) reporting between-group differences and another 14 (21.5%) reporting significant within-group changes. Across 19 of 24 reviews providing quantifiable findings, a median of 64.5% of studies reviewed reported significant effects of PS. In extended review of diabetes, 26 of all 30 studies (86.7%) reported significant impacts of PS, 17 (56.7%) reporting between-group differences and another nine (30.0%) reporting significant within-group changes. Among 19 of these 30 reporting HbA1c data, average reduction was 0.76 points. Studies that did not find effects of PS included other sources of support, implementation or methodological problems, lack of acceptance of interventions, poor fit to recipient needs, and possible harm of unmoderated PS. Across diverse settings, including under-resourced countries and health care systems, PS is effective in improving complex health behaviors in disease prevention and management including in diabetes.

Effects of BDNF Val66Met polymorphism on brain metabolism in Alzheimer's disease.

PubMed

Xu, Cunlu; Wang, Zhenhua; Fan, Ming; Liu, Bing; Song, Ming; Zhen, Xiantong; Jiang, Tianzi

2010-08-23

Earlier studies showed that the Val66Met polymorphisms of the brain-derived neurotrophic factor differentially affect gray matter volume and brain region activities. This study used resting positron emission tomography to investigate the relationship between the polymorphisms of Val66Met and the regional cerebral metabolic rate in the brain. We analyzed the positron emission tomography images of 215 patients from the Alzheimer's Disease Neuroimaging Initiative and found significant differences in the parahippocampal gyrus, superior temporal gyrus, prefrontal cortex, and inferior parietal lobule when comparing Met carriers with noncarriers among both the normal controls and those with mild cognitive impairment. For those with Alzheimer's disease, we also found additional differences in the bilateral insula between the carriers and noncarriers.

Insights into the genetics of gastroesophageal reflux disease (GERD) and GERD-related disorders.

PubMed

Böhmer, A C; Schumacher, J

2017-02-01

Gastroesophageal reflux disease (GERD) is associated with obesity and hiatal hernia, and often precedes the development of Barrett's esophagus (BE) and esophageal adenocarcinoma (EA). Epidemiological studies show that the global prevalence of GERD is increasing. GERD is a multifactorial disease with a complex genetic architecture. Genome-wide association studies (GWAS) have provided initial insights into the genetic background of GERD. The present review summarizes current knowledge of the genetics of GERD and a possible genetic overlap between GERD and BE and EA. The review discusses genes and cellular pathways that have been implicated through GWAS, and provides an outlook on how future molecular research will enhance understanding of GERD pathophysiology. © 2017 John Wiley & Sons Ltd.

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.