Pathomechanisms in Lysosomal Storage Disorders

PubMed Central

Walkley, Steven U.; Vanier, Marie T.

2015-01-01

Lysosomal diseases are inherited metabolic disorders caused by defects in a wide spectrum of lysosomal and a few non-lysosomal proteins. In most cases a single type of primary storage material is identified, which has been used to name and classify the disorders: hence the terms sphingolipidoses, gangliosidoses, mucopolysaccharidoses, glycoproteinoses, and so forth. In addition to this primary storage, however, a host of secondary storage products can also be identified, more often than not having no direct link to the primary protein defect. Lipids - glycosphingolipids and phospholipids, as well as cholesterol - are the most ubiquitous and best studied of these secondary storage materials. While in the past typically considered nonspecific and nonconsequential features of these diseases, newer studies suggest direct links between secondary storage and disease pathogenesis and support the view that understanding all aspects of this sequestration process will provide important insights into the cell biology and treatment of lysosomal disease. PMID:19111580

Quality improvement tools for chronic disease care--more effective processes are less likely to be implemented in developing countries.

PubMed

Hashim, Muhammad Jawad; Prinsloo, Adrianna; Mirza, Deen M

2013-01-01

Chronic disease services may be improved if care management processes (CMPs), such as disease-specific flowsheets and chronic disease registries, are used. The newly industrialized Gulf state health service has underdeveloped primary care but higher diabetes prevalence. This paper's aim is to investigate care management processes in United Arab Emirates (UAE) primary care clinics to explore these issues. A cross-sectional survey using self-administered questionnaires given to family physicians and nurses attending a UAE University workshop was used to collect data. All 38 participants completed the questionnaire: 68 per cent were women and 81 per cent physicians. Care management processes in use included: medical records, 76 per cent; clinical guidelines, 74 per cent; chronic disease care rooms, 74 per cent; disease-specific flowsheets, 61 per cent; medical record audits, 57 per cent; chronic disease nurse-educators, 58 per cent; electronic medical records (EMR), 34 per cent; and incentive plans based on clinical performance, 21 per cent. Only 62 per cent and 48 per cent reported that flowsheets and problem lists, respectively, were completed by physicians. Responses to the open-ended question included using traditional quality improvement (QI) approaches such as continuing education and staff meetings, but not proactive systems such as disease registries and self-management. The study used a small, non-random sample and the survey instrument's psychometric properties were not collected. Chronic disease care CMPs are present in UAE clinics but use is limited. Quality improvement should include disease registries, reminder-tracking systems, patient self-management support and quality incentives. This report highlights the lag regarding adopting more effective CMPs in developing countries.

Ethical and legal issues in the clinical practice of primary health care.

PubMed

Maestro, Francisco Javier; Martinez-Romero, Marcos; Vazquez-Naya, Jose Manuel; Pereira, Javier; Pazos, Alejandro

2013-01-01

Since it was conceived, the notion of primary care has been a crucial concept in health services. Most health care is provided at this level and primary care clinicians have an essential role, both in terms of disease prevention and disease management. During the last decades, primary health care has evolved from a traditional paternalistic model, in which patients played the role of passive recipient of care, towards a situation in which patients are partners involved in the decision making-process. This new context opened a considerable number of new ethical and legal aspects, which need to be comprehensively analyzed and discussed in order to preserve the quality of primary health care all around the world. This work reviews the most important ethical and legal issues in primary health care. Legislation issues are explained in the context of the Spanish Health Services.

CAMBRA: An Examination of Change in the Dental Profession

ERIC Educational Resources Information Center

Young, Douglas

2010-01-01

Dental caries is a disease process, one that will not be eliminated by tooth repair alone. Caries is the most prevalent disease of children and the primary reason for most restorative dental visits in both adults and children. A risk-based approach to managing caries targets those in greatest jeopardy for contracting the disease and provides…

Implementation of cardiovascular disease prevention in primary health care: enhancing understanding using normalisation process theory.

PubMed

Volker, Nerida; Williams, Lauren T; Davey, Rachel C; Cochrane, Thomas; Clancy, Tanya

2017-02-24

The reorientation of primary health care towards prevention is fundamental to addressing the rising burden of chronic disease. However, in Australia, cardiovascular disease prevention practice in primary health care is not generally consistent with existing guidelines. The Model for Prevention study was a whole-of-system cardiovascular disease prevention intervention, with one component being enhanced lifestyle modification support and addition of a health coaching service in the general practice setting. To determine the feasibility of translating intervention outcomes into real world practice, implementation work done by stakeholders was examined using Normalisation Process Theory as a framework. Data was collected through interviews with 40 intervention participants and included general practitioners, practice nurses, practice managers, lifestyle advisors and participants. Data analysis was informed by normalisation process theory constructs. Stakeholders were in agreement that, while prevention is a key function of general practice, it was not their usual work. There were varying levels of engagement with the intervention by practice staff due to staff interest, capacity and turnover, but most staff reconfigured their work for required activities. The Lifestyle Advisors believed staff had varied levels of interest in and understanding of, their service, but most staff felt their role was useful. Patients expanded their existing relationships with their general practice, and most achieved their lifestyle modification goals. While the study highlighted the complex nature of the change required, many of the new or enhanced processes implemented as part of the intervention could be scaled up to improve the systems approach to prevention. Overcoming the barriers to change, such as the perception of CVD prevention as a 'hard sell', is going to rely on improving the value proposition for all stakeholders. The study provided a detailed understanding of the work required to implement a complex cardiovascular disease prevention intervention within general practice. The findings highlighted the need for multiple strategies that engage all stakeholders. Normalisation process theory was a useful framework for guiding change implementation.

[Specificities of the logopenic variant of primary progressive aphasia].

PubMed

Magnin, E; Teichmann, M; Martinaud, O; Moreaud, O; Ryff, I; Belliard, S; Pariente, J; Moulin, T; Vandel, P; Démonet, J-F

2015-01-01

The logopenic variant of primary progressive aphasia is a syndrome with neuropsychological and linguistic specificities, including phonological loop impairment for which diagnosis is currently mainly based on the exclusion of the two other variants, semantic and nonfluent/agrammatic primary progressive aphasia. The syndrome may be underdiagnosed due (1) to mild language difficulties during the early stages of the disease or (2) to being mistaken for mild cognitive impairment or Alzheimer's disease when the evaluation of episodic memory is based on verbal material and (3) finally, it is not uncommon that the disorders are attributed to psychiatric co-morbidities such as, for example, anxiety. Moreover, compared to other variants of primary progressive aphasia, brain abnormalities are different. The left temporoparietal junction is initially affected. Neuropathology and biomarkers (cerebrospinal fluid, molecular amyloid nuclear imaging) frequently reveal Alzheimer's disease. Consequently this variant of primary progressive aphasia does not fall under the traditional concept of frontotemporal lobar degeneration. These distinctive features highlight the utility of correct diagnosis, classification, and use of biomarkers to show the neuropathological processes underlying logopenic primary progressive aphasia. The logopenic variant of primary progressive aphasia is a specific form of Alzheimer's disease frequently presenting a rapid decline; specific linguistic therapies are needed. Further investigation of this syndrome is needed to refine screening, improve diagnostic criteria and better understand the epidemiology and the biological mechanisms involved. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

The Existence of Primary Age-Related Tauopathy Suggests that not all the Cases with Early Braak Stages of Neurofibrillary Pathology are Alzheimer's Disease.

PubMed

Giaccone, Giorgio

2015-01-01

The distinction between Alzheimer's disease (AD) and Primary Age-Related Tauopathy (PART) is a hotly debated issue. As most lines of evidence support the tenet that tau pathology occurs downstream of amyloid-β deposition, it seems reasonable to consider PART as a separate disease process not necessarily related to Aβ and hence AD. Following this view, the early stages of neurofibrillary pathology may not always be the forerunner of diffuse neurofibrillary changes and AD. The ongoing debate further enhances the need for greater caution against any future predictions using tau cerebrospinal fluid and imaging biomarkers.

Managing Chronic Disease in Ontario Primary Care: The Impact of Organizational Factors

PubMed Central

Russell, Grant M.; Dahrouge, Simone; Hogg, William; Geneau, Robert; Muldoon, Laura; Tuna, Meltem

2009-01-01

PURPOSE New approaches to chronic disease management emphasize the need to improve the delivery of primary care services to meet the needs of chronically ill patients. This study (1) assessed whether chronic disease management differed among 4 models of primary health care delivery and (2) identified which practice organizational factors were independently associated with high-quality care. METHODS We undertook a cross-sectional survey with nested qualitative case studies (2 practices per model) in 137 randomly selected primary care practices from 4 delivery models in Ontario Canada: fee for service, capitation, blended payment, and community health centers (CHCs). Practice and clinician surveys were based on the Primary Care Assessment Tool. A chart audit assessed evidence-based care delivery for patients with diabetes, congestive heart failure, and coronary artery disease. Intermediate outcomes were calculated for patients with diabetes and hypertension. Multiple linear regression identified those organizational factors independently associated with chronic disease management. RESULTS Chronic disease management was superior in CHCs. Clinicians in CHCs found it easier than those in the other models to promote high-quality care through longer consultations and interprofessional collaboration. Across the whole sample and independent of model, high-quality chronic disease management was associated with the presence of a nurse-practitioner. It was also associated with lower patient-family physician ratios and when practices had 4 or fewer full-time-equivalent family physicians. CONCLUSIONS The study adds to the literature supporting the value of nurse-practitioners within primary care teams and validates the contributions of Ontario’s CHCs. Our observation that quality of care decreased in larger, busier practices suggests that moves toward larger practices and greater patient-physician ratios may have unanticipated negative effects on processes of care quality. PMID:19597168

Trophic factors in neurologic disease.

PubMed

Stewart, S S; Appel, S H

1988-01-01

Recent studies suggest that diffusible factors released by neural targets enhance the survival, growth, and differentiation of neurons both peripherally and in the central nervous system. Evidence for such trophic factors exists for many of the neural systems involved in the degenerative neurologic diseases Alzheimer's disease, parkinsonism, and amyotrophic lateral sclerosis. It is our hypothesis that for each of these disorders there is both a primary insult and a secondary effect. The primary insult may have multiple etiologies, but the secondary effect is the result of retrograde degeneration. Such retrograde degeneration occurs because of an impairment of trophic factor function or an inadequacy of trophic effects to keep pace with the primary destructive process. Accordingly, it may be possible to exploit such trophic mechanisms to define further the pathobiology of neural degeneration and to develop specific treatments for currently incurable illnesses.

Surrogate endpoints for clinical trials in primary sclerosing cholangitis: Review and results from an International PSC Study Group consensus process.

PubMed

Ponsioen, Cyriel Y; Chapman, Roger W; Chazouillères, Olivier; Hirschfield, Gideon M; Karlsen, Tom H; Lohse, Ansgar W; Pinzani, Massimo; Schrumpf, Erik; Trauner, Michael; Gores, Gregory J

2016-04-01

Primary sclerosing cholangitis (PSC) is a rare, but serious, cholestatic disease for which, to date, no effective therapy exists to halt disease progression toward end-stage liver disease. Clinical trial design to study drugs that improve prognosis is hampered by the relatively low event rate of clinically relevant endpoints. To overcome this shortcoming, there is an urgent need to identify appropriate surrogate endpoints. At present, there are no established surrogate endpoints. This article provides a critical review and describes the results of a consensus process initiated by the International PSC Study Group to delineate appropriate candidate surrogate endpoints at present for clinical trials in this frequently dismal disease. The consensus process resulted in a shortlist of five candidates as surrogate endpoints for measuring disease progression: alkaline phosphatase (ALP); transient elastography (TE); histology; combination of ALP+histology; and bilirubin. Of these, histology, ALP, and TE came out as the most promising. However, the expert panel concluded that no biomarker currently exceeds level 3 validation. Combining multiple endpoints is advisable. At present, there are insufficient data to support level 2 validation for any surrogate endpoint in PSC. Concerted efforts by all stakeholders are highly needed. Novel, promising noninvasive biomarkers are under study and should be incorporated as exploratory endpoints in clinical trials. © 2015 by the American Association for the Study of Liver Diseases.

Understanding the implementation of interventions to improve the management of chronic kidney disease in primary care: a rapid realist review.

PubMed

Tsang, Jung Yin; Blakeman, Tom; Hegarty, Janet; Humphreys, John; Harvey, Gill

2016-04-04

Chronic kidney disease (CKD) is common and a significant marker of morbidity and mortality. Its management in primary care is essential for maintenance of cardiovascular health, avoidance of acute kidney injury (AKI) and delay in progression to end-stage renal disease. Although many guidelines and interventions have been established, there is global evidence of an implementation gap, including variable identification rates and low patient communication and awareness. The objective of this study is to understand the factors enabling and constraining the implementation of CKD interventions in primary care. A rapid realist review was conducted that involved a primary literature search of three databases to identify existing CKD interventions in primary care between the years 2000 and 2014. A secondary search was performed as an iterative process and included bibliographic and grey literature searches of reference lists, authors and research groups. A systematic approach to data extraction using Normalisation Process Theory (NPT) illuminated key mechanisms and contextual factors that affected implementation. Our primary search returned 710 articles that were narrowed down to 18 relevant CKD interventions in primary care. Our findings suggested that effective management of resources (encompassing many types) was a significant contextual factor enabling or constraining the functioning of mechanisms. Three key intervention features were identified from the many that contributed to successful implementation. Firstly, it was important to frame CKD interventions appropriately, such as within the context of cardiovascular health and diabetes. This enabled buy-in and facilitated an understanding of the significance of CKD and the need for intervention. Secondly, interventions that were compatible with existing practices or patients' everyday lives were readily accepted. In contrast, new systems that could not be integrated were abandoned as they were viewed as inconvenient, generating more work. Thirdly, ownership of the feedback process allowed users to make individualised improvements to the intervention to suit their needs. Our rapid realist review identified mechanisms that need to be considered in order to optimise the implementation of interventions to improve the management of CKD in primary care. Further research into the factors that enable prolonged sustainability and cost-effectiveness is required for efficient resource utilisation.

Development of the Champlain primary care cardiovascular disease prevention and management guideline

PubMed Central

Montoya, Lorraine; Liddy, Clare; Hogg, William; Papadakis, Sophia; Dojeiji, Laurie; Russell, Grant; Akbari, Ayub; Pipe, Andrew; Higginson, Lyall

2011-01-01

Abstract Problem addressed A well documented gap remains between evidence and practice for clinical practice guidelines in cardiovascular disease (CVD) care. Objective of program As part of the Champlain CVD Prevention Strategy, practitioners in the Champlain District of Ontario launched a large quality-improvement initiative that focused on increasing the uptake in primary care practice settings of clinical guidelines for heart disease, stroke, diabetes, and CVD risk factors. Program description The Champlain Primary Care CVD Prevention and Management Guideline is a desktop resource for primary care clinicians working in the Champlain District. The guideline was developed by more than 45 local experts to summarize the latest evidence-based strategies for CVD prevention and management, as well as to increase awareness of local community-based programs and services. Conclusion Evidence suggests that tailored strategies are important when implementing specific practice guidelines. This article describes the process of creating an integrated clinical guideline for improvement in the delivery of cardiovascular care. PMID:21673196

Heart Ed 101

ERIC Educational Resources Information Center

Smith, Lynne E.

2008-01-01

Cardiovascular disease is the leading cause of death for men and women in the United States. Risk factors and health behaviors combine over time to contribute to the disease process. College communities provide a unique environment for health promotion, risk reduction, and primary intervention. Heart health should be an integral part of college…

Colonic metastasis from carcinoma of the breast that mimics a primary intestinal cancer.

PubMed

Uygun, Kazim; Kocak, Zafer; Altaner, Semsi; Cicin, Irfan; Tokatli, Fusun; Uzal, Cem

2006-08-31

Although the lung, liver, or bones are the most common location for distant metastases in breast cancer patients, metastases to the intestinal tract are very rarely recognized in the clinic. We will present an unusual case of colonic metastasis from a carcinoma of the breast that mimics a primary intestinal cancer, along with a through review of English language medical literature. Despite the fact that isolated gastrointestinal (GI) metastases are very rare and much less common than benign disease processes or second primaries of the intestinal tract in patients with a history of breast cancer, metastatic disease should be given consideration whenever a patient experiences GI symptoms.

Primary cutaneous melanoma of the scalp: Patterns of recurrence.

PubMed

Sparks, David S; Read, Tavis; Lonne, Michael; Barbour, Andrew P; Wagels, Michael; Bayley, Gerard J; Smithers, B Mark

2017-03-01

Patients with primary melanoma of the scalp have been reported to have worse disease-related outcomes compared with other anatomical regions. There are few studies in the literature specifically addressing recurrence patterns and treatment outcomes for primary scalp melanoma as a discrete anatomical sub-region. We sought to identify key features adversely influencing disease control and survival and to clarify the role of resection plane, margin, and method of reconstruction in the management of this disease process. A retrospective clinical study of medical records was performed evaluating all patients with primary melanoma of the scalp treated at two hospitals in southeast Queensland between 2004 and 2014. A total of 107 patients were eligible for analysis. There were 46 recurrences in 38 patients in the cohort accounting for a recurrence rate of 35.5%. The local recurrence rate was 15.9% with 12 in-transit metastases after diagnosis. Regional and distant recurrence rates were 12.1% and 15%, respectively. At a median follow up of 30.5 months, disease-free survival was 47% and overall survival was also 47%. On multi-variate analysis, the deeper resection plane (sub-galeal) had a lower disease-free survival rate compared with the supra-galeal resection plane (P = 0.032). Our results support the hypothesis that primary scalp melanoma represents a unique aggressive subcategory with high rates of in-transit disease and poor disease-related and survival outcomes. There is a need for robust prospective comparative studies to address the significance of resection plane in the management of patients with scalp melanoma. © 2016 Wiley Periodicals, Inc.

International collaborative project to compare and monitor the nutritional composition of processed foods.

PubMed

Dunford, Elizabeth; Webster, Jacqui; Metzler, Adriana Blanco; Czernichow, Sebastien; Ni Mhurchu, Cliona; Wolmarans, Petro; Snowdon, Wendy; L'Abbe, Mary; Li, Nicole; Maulik, Pallab K; Barquera, Simon; Schoj, Verónica; Allemandi, Lorena; Samman, Norma; de Menezes, Elizabete Wenzel; Hassell, Trevor; Ortiz, Johana; Salazar de Ariza, Julieta; Rahman, A Rashid; de Núñez, Leticia; Garcia, Maria Reyes; van Rossum, Caroline; Westenbrink, Susanne; Thiam, Lim Meng; MacGregor, Graham; Neal, Bruce

2012-12-01

Chronic diseases are the leading cause of premature death and disability in the world with overnutrition a primary cause of diet-related ill health. Excess energy intake, saturated fat, sugar, and salt derived from processed foods are a major cause of disease burden. Our objective is to compare the nutritional composition of processed foods between countries, between food companies, and over time. Surveys of processed foods will be done in each participating country using a standardized methodology. Information on the nutrient composition for each product will be sought either through direct chemical analysis, from the product label, or from the manufacturer. Foods will be categorized into 14 groups and 45 categories for the primary analyses which will compare mean levels of nutrients at baseline and over time. Initial commitments to collaboration have been obtained from 21 countries. This collaborative approach to the collation and sharing of data will enable objective and transparent tracking of processed food composition around the world. The information collected will support government and food industry efforts to improve the nutrient composition of processed foods around the world.

Physiology and pathogenesis of gastroesophageal reflux disease.

PubMed

Mikami, Dean J; Murayama, Kenric M

2015-06-01

Gastroesophageal reflux disease (GERD) is one of the most common problems treated by primary care physicians. Almost 20% of the population in the United States experiences occasional regurgitation, heartburn, or retrosternal pain because of GERD. Reflux disease is complex, and the physiology and pathogenesis are still incompletely understood. However, abnormalities of any one or a combination of the three physiologic processes, namely, esophageal motility, lower esophageal sphincter function, and gastric motility or emptying, can lead to GERD. There are many diagnostic and therapeutic approaches to GERD today, but more studies are needed to better understand this complex disease process. Copyright © 2015 Elsevier Inc. All rights reserved.

Myopathic involvement and mitochondrial pathology in Kennedy disease and in other motor neuron diseases.

PubMed

Orsucci, D; Rocchi, A; Caldarazzo Ienco, E; Alì, G; LoGerfo, A; Petrozzi, L; Scarpelli, M; Filosto, M; Carlesi, C; Siciliano, G; Bonuccelli, U; Mancuso, M

2014-01-01

Kennedy disease (spinal and bulbar muscular atrophy, or SBMA) is a motor neuron disease caused by a CAG expansion in the androgen-receptor (AR) gene. Increasing evidence shows that SBMA may have a primary myopathic component and that mitochondrial dysfunction may have some role in the pathogenesis of this disease. In this article, we review the role of mitochondrial dysfunction and of the mitochondrial genome (mtDNA) in SBMA, and we present the illustrative case of a patient who presented with increased CK levels and exercise intolerance. Molecular analysis led to definitive diagnosis of SBMA, whereas muscle biopsy showed a mixed myopathic and neurogenic process with "mitochondrial features" and multiple mtDNA deletions, supporting some role of mitochondria in the pathogenesis of the myopathic component of Kennedy disease. Furthermore, we briefly review the role of mitochondrial dysfunction in two other motor neuron diseases (namely spinal muscular atrophy and amyotrophic lateral sclerosis). Most likely, in most cases mtDNA does not play a primary role and it is involved subsequently. MtDNA deletions may contribute to the neurodegenerative process, but the exact mechanisms are still unclear. It will be important to develop a better understanding of the role of mitochondrial dysfunction in motoneuron diseases, since it may lead to the development of more effective strategies for the treatment of this devastating disorder.

Continuous cell lines from the Muscovy duck as potential replacement for primary cells in the production of avian vaccines.

PubMed

Jordan, Ingo; John, Katrin; Höwing, Kristin; Lohr, Verena; Penzes, Zoltán; Gubucz-Sombor, Erzsébet; Fu, Yan; Gao, Peng; Harder, Timm; Zádori, Zoltán; Sandig, Volker

2016-01-01

Veterinary vaccines contribute to food security, interrupt zoonotic transmissions, and help to maintain overall health in livestock. Although vaccines are usually cost-effective, their adoption depends on a multitude of factors. Because poultry vaccines are usually given to birds with a short life span, very low production cost per dose is one important challenge. Other hurdles are to ensure a consistent and reliable supply of very large number of doses, and to have flexible production processes to accommodate a range of different pathogens and dosage requirements. Most poultry vaccines are currently being produced on primary avian cells derived from chicken or waterfowl embryos. This production system is associated with high costs, logistic complexities, rigid intervals between harvest and production, and supply limitations. We investigated whether the continuous cell lines Cairina retina and CR.pIX may provide a substrate independent of primary cell cultures or embryonated eggs. Viruses examined for replication in these cell lines are strains associated with, or contained in vaccines against egg drop syndrome, Marek's disease, Newcastle disease, avian influenza, infectious bursal disease and Derzsy's disease. Each of the tested viruses required the development of unique conditions for replication that are described here and can be used to generate material for in vivo efficacy studies and to accelerate transfer of the processes to larger production volumes.

Understanding metal homeostasis in primary cultured neurons. Studies using single neuron subcellular and quantitative metallomics.

PubMed

Colvin, Robert A; Lai, Barry; Holmes, William R; Lee, Daewoo

2015-07-01

The purpose of this study was to demonstrate how single cell quantitative and subcellular metallomics inform us about both the spatial distribution and cellular mechanisms of metal buffering and homeostasis in primary cultured neurons from embryonic rat brain, which are often used as models of human disease involving metal dyshomeostasis. The present studies utilized synchrotron radiation X-ray fluorescence (SRXRF) and focused primarily on zinc and iron, two abundant metals in neurons that have been implicated in the pathogenesis of neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease. Total single cell contents for calcium, iron, zinc, copper, manganese, and nickel were determined. Resting steady state zinc showed a diffuse distribution in both soma and processes, best defined by the mass profile of the neuron with an enrichment in the nucleus compared with the cytoplasm. Zinc buffering and homeostasis was studied using two modes of cellular zinc loading - transporter and ionophore (pyrithione) mediated. Single neuron zinc contents were shown to statistically significantly increase by either loading method - ionophore: 160 million to 7 billion; transporter 160 million to 280 million atoms per neuronal soma. The newly acquired and buffered zinc still showed a diffuse distribution. Soma and processes have about equal abilities to take up zinc via transporter mediated pathways. Copper levels are distributed diffusely as well, but are relatively higher in the processes relative to zinc levels. Prior studies have observed iron puncta in certain cell types, but others have not. In the present study, iron puncta were characterized in several primary neuronal types. The results show that iron puncta could be found in all neuronal types studied and can account for up to 50% of the total steady state content of iron in neuronal soma. Although other metals can be present in iron puncta, they are predominantly iron containing and do not appear to be associated with ferritin cages or transferrin receptor endosomes. The iron content and its distribution in puncta were similar in all neuron types studied including primary dopaminergic neurons. In summary, quantitative measurements of steady state metal levels in single primary cultured neurons made possible by SRXRF analyses provide unique information on the relative levels of each metal in neuronal soma and processes, subcellular location of zinc loads, and have confirmed and extended the characterization of heretofore poorly understood cytoplasmic iron puncta.

Professional commitment to changing chronic illness care: results from disease management programmes.

PubMed

Lemmens, Karin; Strating, Mathilde; Huijsman, Robbert; Nieboer, Anna

2009-08-01

The aim of this exploratory study was to investigate to what extent primary care professionals are able to change their systems for delivering care to chronic obstructive pulmonary disease (COPD) patients and what professional and organizational factors are associated with the degree of process implementation. Quasi-experimental design with 1 year follow-up after intervention. Three regional COPD management programmes in the Netherlands, in which general practices cooperated with regional hospitals. All participating primary care professionals (n = 52). COPD management programme. Professional commitment, organizational context and degree of process implementation. Professionals significantly changed their systems for delivering care to COPD patients, namely self-management support, decision support, delivery system design and clinical information systems. Associations were found between organizational factors, professional commitment and changes in processes of care. Group culture and professional commitment appeared to be, to a moderate degree, predictors of process implementation. COPD management was effective; all processes improved significantly. Moreover, theoretically expected associations between organizational context and professional factors with the implementation of COPD management were indeed confirmed to some extent. Group culture and professional commitment are important facilitators.

Processing emotion from abstract art in frontotemporal lobar degeneration

PubMed Central

Cohen, Miriam H.; Carton, Amelia M.; Hardy, Christopher J.; Golden, Hannah L.; Clark, Camilla N.; Fletcher, Phillip D.; Jaisin, Kankamol; Marshall, Charles R.; Henley, Susie M.D.; Rohrer, Jonathan D.; Crutch, Sebastian J.; Warren, Jason D.

2016-01-01

Abstract art may signal emotions independently of a biological or social carrier: it might therefore constitute a test case for defining brain mechanisms of generic emotion decoding and the impact of disease states on those mechanisms. This is potentially of particular relevance to diseases in the frontotemporal lobar degeneration (FTLD) spectrum. These diseases are often led by emotional impairment despite retained or enhanced artistic interest in at least some patients. However, the processing of emotion from art has not been studied systematically in FTLD. Here we addressed this issue using a novel emotional valence matching task on abstract paintings in patients representing major syndromes of FTLD (behavioural variant frontotemporal dementia, n=11; sematic variant primary progressive aphasia (svPPA), n=7; nonfluent variant primary progressive aphasia (nfvPPA), n=6) relative to healthy older individuals (n=39). Performance on art emotion valence matching was compared between groups taking account of perceptual matching performance and assessed in relation to facial emotion matching using customised control tasks. Neuroanatomical correlates of art emotion processing were assessed using voxel-based morphometry of patients' brain MR images. All patient groups had a deficit of art emotion processing relative to healthy controls; there were no significant interactions between syndromic group and emotion modality. Poorer art emotion valence matching performance was associated with reduced grey matter volume in right lateral occopitotemporal cortex in proximity to regions previously implicated in the processing of dynamic visual signals. Our findings suggest that abstract art may be a useful model system for investigating mechanisms of generic emotion decoding and aesthetic processing in neurodegenerative diseases. PMID:26748236

Atherosclerotic Cardiovascular Disease Beginning in Childhood

PubMed Central

2010-01-01

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

A national surveillance project on chronic kidney disease management in Canadian primary care: a study protocol.

PubMed

Bello, Aminu K; Ronksley, Paul E; Tangri, Navdeep; Singer, Alexander; Grill, Allan; Nitsch, Dorothea; Queenan, John A; Lindeman, Cliff; Soos, Boglarka; Freiheit, Elizabeth; Tuot, Delphine; Mangin, Dee; Drummond, Neil

2017-08-04

Effective chronic disease care is dependent on well-organised quality improvement (QI) strategies that monitor processes of care and outcomes for optimal care delivery. Although healthcare is provincially/territorially structured in Canada, there are national networks such as the Canadian Primary Care Sentinel Surveillance Network (CPCSSN) as important facilitators for national QI-based studies to improve chronic disease care. The goal of our study is to improve the understanding of how patients with chronic kidney disease (CKD) are managed in primary care and the variation across practices and provinces and territories to drive improvements in care delivery. The CPCSSN database contains anonymised health information from the electronic medical records for patients of participating primary care practices (PCPs) across Canada (n=1200). The dataset includes information on patient sociodemographics, medications, laboratory results and comorbidities. Leveraging validated algorithms, case definitions and guidelines will help define CKD and the related processes of care, and these enable us to: (1) determine prevalent CKD burden; (2) ascertain the current practice pattern on risk identification and management of CKD and (3) study variation in care indicators (eg, achievement of blood pressure and proteinuria targets) and referral pattern for specialist kidney care. The process of care outcomes will be stratified across patients' demographics as well as provider and regional (provincial/territorial) characteristics. The prevalence of CKD stages 3-5 will be presented as age-sex standardised prevalence estimates stratified by province and as weighted averages for population rates with 95% CIs using census data. For each PCP, age-sex standardised prevalence will be calculated and compared with expected standardised prevalence estimates. The process-based outcomes will be defined using established methods. The CPCSSN is committed to high ethical standards when dealing with individual data collected, and this work is reviewed and approved by the Network Scientific Committee. The results will be published in peer-reviewed journals and presented at relevant national and international scientific meetings. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Design of a Recommendation System for Adding Support in the Treatment of Chronic Patients.

PubMed

Torkar, Simon; Benedik, Peter; Rajkovič, Uroš; Šušteršič, Olga; Rajkovič, Vladislav

2016-01-01

Rapid growth of chronic disease cases around the world is adding pressure on healthcare providers to ensure a structured patent follow-up during chronic disease management process. In response to the increasing demand for better chronic disease management and improved health care efficiency, nursing roles have been specialized or enhanced in the primary health care setting. Nurses become key players in chronic disease management process. Study describes a system to help nurses manage the care process of patient with chronic disease. It supports focusing nurse's attention on those resources/solutions that are likely to be most relevant to their particular situation/problem in nursing domain. System is based on multi-relational property graph representing a flexible modeling construct. Graph allows modeling a nursing ontology and the indices that partition domain into an efficient, searchable space where the solution to a problem is seen as abstractly defined traversals through its vertices and edges.

Liver alkaline phosphatase: a missing link between choleresis and biliary inflammation.

PubMed

Poupon, Raoul

2015-06-01

Several lines of evidence show that serum alkaline phosphatase (AP) is not only a signpost of cholestasis but also a surrogate marker of the severity of primary biliary cirrhosis and primary sclerosing cholangitis. In the present opinion article, we review and discuss the putative role of liver AP in health and in cholestatic diseases. In inflammatory cholestatic conditions, loss of activity of liver AP (resulting from its relocation from canaliculi and the acidic milieu) might promote hyper-adenosine triphosphate-bilia, lipopolysaccharide overload, and subsequent exacerbation and perpetuation of inflammation. Drugs that can restore the polarity of hepatocytes and canalicular export of bile acids or act as bile alkalinity modifiers are predicted to exert anti-inflammatory effects and to benefit both primary biliary cirrhosis and primary sclerosing cholangitis. Oral administration of intestinal AP could be a valid therapeutic intervention that deserves further study under experimental conditions as well as in human diseases. Overall, the key role of the liver microenvironment that might shape the different facets of the inflammatory processes in fibrosing cholangiopathies is highlighted. © 2015 by the American Association for the Study of Liver Diseases.

A tale of two audits: statistical process control for improving diabetes care in primary care settings.

PubMed

Al-Hussein, Fahad Abdullah

2008-01-01

Diabetes constitutes a major burden of disease globally. Both primary and secondary prevention need to improve in order to face this challenge. Improving management of diabetes in primary care is therefore of fundamental importance. The objective of these series of audits was to find means of improving diabetes management in chronic disease mini-clinics in primary health care. In the process, we were able to study the effect and practical usefulness of different audit designs - those measuring clinical outcomes, process of care, or both. King Saud City Family and Community Medicine Centre, Saudi National Guard Health Affairs in Riyadh city, Saudi Arabia. Simple random samples of 30 files were selected every two weeks from a sampling frame of file numbers for all diabetes clients seen over the period. Information was transferred to a form, entered on the computer and an automated response was generated regarding the appropriateness of management, a criterion mutually agreed upon by care providers. The results were plotted on statistical process control charts, p charts, displayed for all employees. Data extraction, archiving, entry, analysis, plotting and design and preparation of p charts were managed by nursing staff specially trained for the purpose by physicians with relevant previous experience. Audit series with mixed outcome and process measures failed to detect any changes in the proportion of non-conforming cases over a period of one year. The process measures series, on the other hand, showed improvement in care corresponding to a reduction in the proportion non-conforming by 10% within a period of 3 months. Non-conformities dropped from a mean of 5.0 to 1.4 over the year (P < 0.001). It is possible to improve providers' behaviour regarding implementation of given guidelines through periodic process audits and feedbacks. Frequent process audits in the context of statistical process control should be supplemented with concurrent outcome audits, once or twice a year.

Disease management.

PubMed Central

Hunter, D. J.; Fairfield, G.

1997-01-01

The disease management approach to patient care seeks to coordinate resources across the healthcare delivery system. The growing interest in evidence based medicine and outcomes, and a commitment to integrated care across the primary, secondary, and community care sectors, all contribute to making disease management an attractive idea. A combination of patient education, provider use of practice guidelines, appropriate consultation, and supplies of drugs and ancillary services all come together in the disease management process. But its effectiveness is largely untested, so evaluation is essential. PMID:9233330

Modeling human gastrointestinal inflammatory diseases using microphysiological culture systems.

PubMed

Hartman, Kira G; Bortner, James D; Falk, Gary W; Ginsberg, Gregory G; Jhala, Nirag; Yu, Jian; Martín, Martín G; Rustgi, Anil K; Lynch, John P

2014-09-01

Gastrointestinal illnesses are a significant health burden for the US population, with 40 million office visits each year for gastrointestinal complaints and nearly 250,000 deaths. Acute and chronic inflammations are a common element of many gastrointestinal diseases. Inflammatory processes may be initiated by a chemical injury (acid reflux in the esophagus), an infectious agent (Helicobacter pylori infection in the stomach), autoimmune processes (graft versus host disease after bone marrow transplantation), or idiopathic (as in the case of inflammatory bowel diseases). Inflammation in these settings can contribute to acute complaints (pain, bleeding, obstruction, and diarrhea) as well as chronic sequelae including strictures and cancer. Research into the pathophysiology of these conditions has been limited by the availability of primary human tissues or appropriate animal models that attempt to physiologically model the human disease. With the many recent advances in tissue engineering and primary human cell culture systems, it is conceivable that these approaches can be adapted to develop novel human ex vivo systems that incorporate many human cell types to recapitulate in vivo growth and differentiation in inflammatory microphysiological environments. Such an advance in technology would improve our understanding of human disease progression and enhance our ability to test for disease prevention strategies and novel therapeutics. We will review current models for the inflammatory and immunological aspects of Barrett's esophagus, acute graft versus host disease, and inflammatory bowel disease and explore recent advances in culture methodologies that make these novel microphysiological research systems possible. © 2014 by the Society for Experimental Biology and Medicine.

Sensing a Sensor: Identifying the Mechanosensory Function of Primary Cilia

PubMed Central

Prasad, Rahul M.; Jin, Xingjian; Nauli, Surya M.

2014-01-01

Over the past decade, primary cilia have emerged as the premier means by which cells sense and transduce mechanical stimuli. Primary cilia are sensory organelles that have been shown to be vitally involved in the mechanosensation of urine in the renal nephron, bile in the hepatic biliary system, digestive fluid in the pancreatic duct, dentin in dental pulp, lacunocanalicular fluid in bone and cartilage, and blood in vasculature. The prevalence of primary cilia among mammalian cell types is matched by the tremendously varied disease states caused by both structural and functional defects in cilia. In the process of delineating the mechanisms behind these disease states, calcium fluorimetry has been widely utilized as a means of quantifying ciliary function to both fluid flow and pharmacological agents. In this review, we will discuss the approaches used in associating calcium levels to cilia function. PMID:24839551

Redesigning the care of fragility fracture patients to improve osteoporosis management: a health care improvement project.

PubMed

Harrington, J Timothy; Barash, Harvey L; Day, Sherry; Lease, Joellen

2005-04-15

To develop new processes that assure more reliable, population-based care of fragility fracture patients. A 4-year clinical improvement project was performed in a multispecialty, community practice health system using evidence-based guidelines and rapid cycle process improvement methods (plan-do-study-act cycles). Prior to this project, appropriate osteoporosis care was provided to only 5% of our 1999 hip fracture patients. In 2001, primary physicians were provided prompts about appropriate care (cycle 1), which resulted in improved care for only 20% of patients. A process improvement pilot in 2002 (cycle 2) and full program implementation in 2003 (cycle 3) have assured osteoporosis care for all willing and able patients with any fragility fracture. Altogether, 58% of 2003 fragility fracture patients, including 46% of those with hip fracture, have had a bone measurement, have been assigned to osteoporosis care with their primary physician or a consultant, and are being monitored regularly. Only 19% refused osteoporosis care. Key process improvements have included using orthopedic billings to identify patients, referring patients directly from orthopedics to an osteoporosis care program, organizing care with a nurse manager and process management computer software, assigning patients to primary or consultative physician care based on disease severity, and monitoring adherence to therapy by telephone. Reliable osteoporosis care is achievable by redesigning clinical processes. Performance data motivate physicians to reconsider traditional approaches. Improving the care of osteoporosis and other chronic diseases requires coordinated care across specialty boundaries and health system support.

Point-of-Care Diagnostics in Low-Resource Settings and Their Impact on Care in the Age of the Noncommunicable and Chronic Disease Epidemic.

PubMed

Weigl, Bernhard H; Neogi, Tina; McGuire, Helen

2014-06-01

The emergence of point-of-care (POC) diagnostics specifically designed for low-resource settings coupled with the rapid increase in need for routine care of patients with chronic diseases should prompt reconsideration of how health care can be delivered most beneficially and cost-effectively in developing countries. Bolstering support for primary care to provide rapid and appropriate integrated acute and chronic care treatment may be a possible solution. POC diagnostics can empower local and primary care providers and enable them to make better clinical decisions. This article explores the opportunity for POC diagnostics to strengthen primary care and chronic disease diagnosis and management in a low-resource setting (LRS) to deliver appropriate, consistent, and integrated care. We analyze the requirements of resource-appropriate chronic disease care, the characteristics of POC diagnostics in LRS versus the developed world, the many roles of diagnostics in the care continuum in LRS, and the process and economics of developing LRS-compatible POC diagnostics. © 2013 Society for Laboratory Automation and Screening.

Gastroesophageal reflux disease: A clinical overview for primary care physicians.

PubMed

Pandit, Sudha; Boktor, Moheb; Alexander, Jonathan S; Becker, Felix; Morris, James

2018-03-01

GERD is among the most common outpatient disease processes encountered by clinicians on a daily basis. This review provides insights about how to approach GERD in terms of disease management and treatment. Review articles were searched using PUBMED and MEDLINE using criteria that included English language articles published in the last 5 years concerning studies carried out only in humans. The key words used in the searches were GERD, PPI, and erosive esophagitis. Recommendations from the American College of Gastroenterology are also included in this manuscript. The search resulted in ∼260 articles. The manuscript brings together and presents the results of recent recommendations from professional societies and recently published review articles on GERD. GERD is one of the most common diagnoses made by gastroenterologists and primary care physicians. It is important to recognize the typical and atypical presentations of GERD. This paper helps primary care physicians understand the disease's pathophysiology, and when, how, and with what to treat GERD before referring patients to gastroenterologists or surgeons. Copyright © 2017 Elsevier B.V. All rights reserved.

2017 Guidelines for the management of arterial hypertension in primary health care in Portuguese-speaking countries.

PubMed

Oliveira, Gláucia Maria Moraes de; Mendes, Miguel; Malachias, Marcus Vinícius Bolívar; Morais, João; Filho, Osni Moreira; Coelho, Armando Serra; Capingana, Daniel Pires; Azevedo, Vanda; Soares, Irenita; Menete, Alda; Ferreira, Beatriz; Soares, Miryan Bandeira Dos Prazeres Cassandra; Fernandes, Mário

2017-11-01

The World Health Organization goal's to reduce mortality due to chronic non-communicable diseases by 2% per year demands a huge effort from member countries. This challenge for health professionals requires global political action on implementation of social measures, with cost-effective population interventions to reduce chronic non-communicable diseases and their risk factors. Systemic arterial hypertension is highly prevalent in Portuguese-speaking countries, and is a major risk factor for complications such as stroke, acute myocardial infarction and chronic kidney disease, rivaling dyslipidemia and obesity in importance for the development of atherosclerotic disease. Joint actions to implement primary prevention measures can reduce outcomes related to hypertensive disease, especially ischemic heart disease and stroke. It is essential to ensure the implementation of guidelines for the management of systemic hypertension via a continuous process involving educational actions, lifestyle changes and guaranteed access to pharmacological treatment. Copyright © 2017 Sociedade Portuguesa de Cardiologia. Publicado por Elsevier España, S.L.U. All rights reserved.

Quality of care for patients with non-communicable diseases in the Dedza District, Malawi

PubMed Central

Wood, Rachel; Der Merwe, Lisa Van; Mash, Robert

2015-01-01

Introduction In Malawi, non-communicable diseases (NCDs) are thought to cause 28% of deaths in adults. The aim of this study was to establish the extent of primary care morbidity related to NCDs, as well as to audit the quality of care, in the primary care setting of Dedza District, central Malawi. Methods This study was a baseline audit using clinic registers and a questionnaire survey of senior health workers at 5 clinics, focusing on care for hypertension, diabetes, asthma and epilepsy Results A total of 82 581 consultations were recorded, of which 2489 (3.0%) were for the selected NCDs. Only 5 out of 32 structural criteria were met at all 5 clinics and 9 out of 29 process criteria were never performed at any clinic. The only process criteria performed at all five clinics was measurement of blood pressure. The staff's knowledge on NCDs was basic and the main barriers to providing quality care were lack of medication and essential equipment, inadequate knowledge and guidelines, fee-for-service at two clinics, geographic inaccessibility and lack of confidence in the primary health care system by patients. Conclusion Primary care morbidity from NCDs is currently low, although other studies suggest a significant burden of disease. This most likely represents a lack of utilisation, recognition, diagnosis and ability to manage patients with NCDs. Quality of care is poor due to a lack of essential resources, guidelines, and training. PMID:26245609

Understanding the management of early-stage chronic kidney disease in primary care: a qualitative study.

PubMed

Blakeman, Tom; Protheroe, Joanne; Chew-Graham, Carolyn; Rogers, Anne; Kennedy, Anne

2012-04-01

Primary care is recognised to have an important role in the delivery of care for people with chronic kidney disease (CKD). However, there is evidence that CKD management is currently suboptimal, with a range of practitioner concerns about its management. To explore processes underpinning the implementation of CKD management in primary care. Qualitative study in general practices participating in a chronic kidney disease collaborative undertaken as part of the National Institute for Health Research (NIHR) Collaboration for Leadership in Applied Health Research and Care (CLAHRC) for Greater Manchester. Semi-structured interviews were conducted with GPs and practice nurses (n = 21). Normalisation Process Theory provided a framework for generation and analysis of the data. A predominant theme was anxiety about the disclosure of early-stage CKD with patients. The tensions experienced related to identifying and discussing CKD in older people and patients with stage 3A, embedding early-stage CKD within vascular care, and the distribution of work within the practice team. Participants provided accounts of work undertaken to resolve the difficulties encountered, with efforts having tended to focus on reassuring patients. Analysis also highlighted how anxiety surrounding disclosure influenced, and was shaped by, the organisation of care for people with CKD and associated long-term conditions. Offering reassurance alone may be of limited benefit, and current management of early-stage CKD in primary care may miss opportunities to address susceptibility to kidney injury, improve self-management of vascular conditions, and improve the management of multimorbidity.

Recognising meningococcal disease in primary care: qualitative study of how general practitioners process clinical and contextual information.

PubMed

Granier, S; Owen, P; Pill, R; Jacobson, L

1998-01-24

To describe the presentation of meningococcal disease in primary care; to explore how general practitioners process clinical and contextual information in children with meningococcal disease; and to describe how this information affects management. Qualitative analysis of semistructured interviews. General practices in South Glamorgan. 26 general practitioners who between January 1994 and December 1996 admitted 31 children (under 16 years of age) in whom meningococcal disease was diagnosed. Categories of clinical rules and techniques used by general practitioners in processing each case. 22 children had rashes; in 16 of them the rashes were non-blanching. When present, a haemorrhagic rash was the most important factor in the doctor's decision to admit a child. 22 children had clinical features not normally expected in children with acute self limiting illnesses--for example, lethargy, poor eye contact, altered mental states, pallor with a high temperature, and an abnormal cry. Contextual information, such as knowledge of parents' consultation patterns and their normal degree of anxiety, played an important part in the management decisions in 15 cases. Use of penicillin was associated with the certainty of diagnosis and the presence and type of haemorrhagic rash. The key clinical feature of meningococcal disease--a haemorrhagic rash--was present in only half of the study children. The general practitioners specifically hunted for the rash in some ill children, but doctors should not be deterred from diagnosing meningococcal disease and starting antibiotic treatment if the child is otherwise well, if the rash has an unusual or scanty distribution, or if the rash is non-haemorrhagic.

Processing emotion from abstract art in frontotemporal lobar degeneration.

PubMed

Cohen, Miriam H; Carton, Amelia M; Hardy, Christopher J; Golden, Hannah L; Clark, Camilla N; Fletcher, Phillip D; Jaisin, Kankamol; Marshall, Charles R; Henley, Susie M D; Rohrer, Jonathan D; Crutch, Sebastian J; Warren, Jason D

2016-01-29

art may signal emotions independently of a biological or social carrier: it might therefore constitute a test case for defining brain mechanisms of generic emotion decoding and the impact of disease states on those mechanisms. This is potentially of particular relevance to diseases in the frontotemporal lobar degeneration (FTLD) spectrum. These diseases are often led by emotional impairment despite retained or enhanced artistic interest in at least some patients. However, the processing of emotion from art has not been studied systematically in FTLD. Here we addressed this issue using a novel emotional valence matching task on abstract paintings in patients representing major syndromes of FTLD (behavioural variant frontotemporal dementia, n=11; sematic variant primary progressive aphasia (svPPA), n=7; nonfluent variant primary progressive aphasia (nfvPPA), n=6) relative to healthy older individuals (n=39). Performance on art emotion valence matching was compared between groups taking account of perceptual matching performance and assessed in relation to facial emotion matching using customised control tasks. Neuroanatomical correlates of art emotion processing were assessed using voxel-based morphometry of patients' brain MR images. All patient groups had a deficit of art emotion processing relative to healthy controls; there were no significant interactions between syndromic group and emotion modality. Poorer art emotion valence matching performance was associated with reduced grey matter volume in right lateral occopitotemporal cortex in proximity to regions previously implicated in the processing of dynamic visual signals. Our findings suggest that abstract art may be a useful model system for investigating mechanisms of generic emotion decoding and aesthetic processing in neurodegenerative diseases. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

DISINFECTION

EPA Science Inventory

The primary goal of the disinfection process in drinking water treatment is the inactivation of microbial pathogens. These pathogens comprise a diverse group of organisms which serve as the etiological agents of waterborne disease. Included in this group are bacterial, viral and ...

Brain-Specific Cytoskeletal Damage Markers in Cerebrospinal Fluid: Is There a Common Pattern between Amyotrophic Lateral Sclerosis and Primary Progressive Multiple Sclerosis?

PubMed

Abdelhak, Ahmed; Junker, Andreas; Brettschneider, Johannes; Kassubek, Jan; Ludolph, Albert C; Otto, Markus; Tumani, Hayrettin

2015-07-31

Many neurodegenerative disorders share a common pathophysiological pathway involving axonal degeneration despite different etiological triggers. Analysis of cytoskeletal markers such as neurofilaments, protein tau and tubulin in cerebrospinal fluid (CSF) may be a useful approach to detect the process of axonal damage and its severity during disease course. In this article, we review the published literature regarding brain-specific CSF markers for cytoskeletal damage in primary progressive multiple sclerosis and amyotrophic lateral sclerosis in order to evaluate their utility as a biomarker for disease progression in conjunction with imaging and histological markers which might also be useful in other neurodegenerative diseases associated with affection of the upper motor neurons. A long-term benefit of such an approach could be facilitating early diagnostic and prognostic tools and assessment of treatment efficacy of disease modifying drugs.

Brain-Specific Cytoskeletal Damage Markers in Cerebrospinal Fluid: Is There a Common Pattern between Amyotrophic Lateral Sclerosis and Primary Progressive Multiple Sclerosis?

PubMed Central

Abdelhak, Ahmed; Junker, Andreas; Brettschneider, Johannes; Kassubek, Jan; Ludolph, Albert C.; Otto, Markus; Tumani, Hayrettin

2015-01-01

Many neurodegenerative disorders share a common pathophysiological pathway involving axonal degeneration despite different etiological triggers. Analysis of cytoskeletal markers such as neurofilaments, protein tau and tubulin in cerebrospinal fluid (CSF) may be a useful approach to detect the process of axonal damage and its severity during disease course. In this article, we review the published literature regarding brain-specific CSF markers for cytoskeletal damage in primary progressive multiple sclerosis and amyotrophic lateral sclerosis in order to evaluate their utility as a biomarker for disease progression in conjunction with imaging and histological markers which might also be useful in other neurodegenerative diseases associated with affection of the upper motor neurons. A long-term benefit of such an approach could be facilitating early diagnostic and prognostic tools and assessment of treatment efficacy of disease modifying drugs. PMID:26263977

Systematic review of integrated models of health care delivered at the primary-secondary interface: how effective is it and what determines effectiveness?

PubMed

Mitchell, Geoffrey K; Burridge, Letitia; Zhang, Jianzhen; Donald, Maria; Scott, Ian A; Dart, Jared; Jackson, Claire L

2015-01-01

Integrated multidisciplinary care is difficult to achieve between specialist clinical services and primary care practitioners, but should improve outcomes for patients with chronic and/or complex chronic physical diseases. This systematic review identifies outcomes of different models that integrate specialist and primary care practitioners, and characteristics of models that delivered favourable clinical outcomes. For quality appraisal, the Cochrane Risk of Bias tool was used. Data are presented as a narrative synthesis due to marked heterogeneity in study outcomes. Ten studies were included. Publication bias cannot be ruled out. Despite few improvements in clinical outcomes, significant improvements were reported in process outcomes regarding disease control and service delivery. No study reported negative effects compared with usual care. Economic outcomes showed modest increases in costs of integrated primary-secondary care. Six elements were identified that were common to these models of integrated primary-secondary care: (1) interdisciplinary teamwork; (2) communication/information exchange; (3) shared care guidelines or pathways; (4) training and education; (5) access and acceptability for patients; and (6) a viable funding model. Compared with usual care, integrated primary-secondary care can improve elements of disease control and service delivery at a modestly increased cost, although the impact on clinical outcomes is limited. Future trials of integrated care should incorporate design elements likely to maximise effectiveness.

Treatment and recovery.

PubMed

Raia, Susan

2005-01-01

Addiction is a chronic, progressive, fatal disease. It is a primary disease, not caused by any other disease process. It has recognizable symptoms that if left untreated, can lead to premature death, deterioration of physical conditions, social withdrawal and disintegration of all support systems. The family and co-workers are affected as well. There is no cure, but we know that treatment works! Don't stand by while someone you care about needs help. Nurses helping nurses, let's take care of our own.

Development and implementation of an integrated chronic disease model in South Africa: lessons in the management of change through improving the quality of clinical practice

PubMed Central

Asmall, Shaidah

2015-01-01

Background South Africa is facing a complex burden of disease arising from a combination of chronic infectious illness and non-communicable diseases. As the burden of chronic diseases (communicable and non-communicable) increases, providing affordable and effective care to the increasing numbers of chronic patients will be an immense challenge. Methods The framework recommended by the Medical Research Council of the United Kingdom for the development and evaluation of complex health interventions was used to conceptualise the intervention. The breakthrough series was utilised for the implementation process. These two frameworks were embedded within the clinical practice improvement model that served as the overarching framework for the development and implementation of the model. Results The Chronic Care Model was ideally suited to improve the facility component and patient experience; however, the deficiencies in other aspects of the health system building blocks necessitated a hybrid model. An integrated chronic disease management model using a health systems approach was initiated across 42 primary health care facilities. The interventions were implemented in a phased approach using learning sessions and action periods to introduce the planned and targeted changes. Conclusion The implementation of the integrated chronic disease management model is feasible at primary care in South Africa provided that systemic challenges and change management are addressed during the implementation process. PMID:26528101

Development and implementation of an integrated chronic disease model in South Africa: lessons in the management of change through improving the quality of clinical practice.

PubMed

Mahomed, Ozayr Haroon; Asmall, Shaidah

2015-01-01

South Africa is facing a complex burden of disease arising from a combination of chronic infectious illness and non-communicable diseases. As the burden of chronic diseases (communicable and non-communicable) increases, providing affordable and effective care to the increasing numbers of chronic patients will be an immense challenge. The framework recommended by the Medical Research Council of the United Kingdom for the development and evaluation of complex health interventions was used to conceptualise the intervention. The breakthrough series was utilised for the implementation process. These two frameworks were embedded within the clinical practice improvement model that served as the overarching framework for the development and implementation of the model. The Chronic Care Model was ideally suited to improve the facility component and patient experience; however, the deficiencies in other aspects of the health system building blocks necessitated a hybrid model. An integrated chronic disease management model using a health systems approach was initiated across 42 primary health care facilities. The interventions were implemented in a phased approach using learning sessions and action periods to introduce the planned and targeted changes. The implementation of the integrated chronic disease management model is feasible at primary care in South Africa provided that systemic challenges and change management are addressed during the implementation process.

Sleep Disorders in Childhood Neurological Diseases

PubMed Central

Liu, Zhao

2017-01-01

Sleep problems are frequently addressed as a primary or secondary concern during the visit to the pediatric neurology clinic. Sleep disorders can mimic other neurologic diseases (e.g., epilepsy and movement disorders), and this adds challenges to the diagnostic process. Sleep disorders can significantly affect the quality of life and functionality of children in general and those with comorbid neurological diseases in particular. Understanding the pathophysiology of sleep disorders, recognizing the implications of sleep disorder in children with neurologic diseases and behavioral difficulties, and early intervention continue to evolve resulting in better neurocognitive outcomes. PMID:28937639

The role of the cilium in hereditary tumor predisposition syndromes

PubMed Central

Klasson, Timothy D.; Giles, Rachel H.

2014-01-01

The primary cilium is a highly conserved cell organelle that is closely connected to processes involved in cell patterning and replication. Amongst their many functions, cilia act as “signal towers” through which cell-cell signaling cascades pass. Dysfunction of cilia or the myriad processes that are connected with cilium function can lead to disease. Due to the sheer number of cellular processes that at some point involve the primary cilium, the effects of misregulation are highly heterogeneous between different cell populations. However, because of the importance of primary cilia in the development, growth, patterning and orientation of cells and tissues, a common thread has emerged in which defective cilia can lead to disorganization, which can contribute to the growth of neoplasms, including cancer and pre-cancerous phenotypes. Because cilia are so vital for signaling during cell replication and the cell fate decisions that are important in childhood growth, symptoms often arise early in life. Here we review recent work connecting misregulation of the primary cilium with tumor formation in a variety of tissues in the developing body, with a particular focus on the syndromes in which classic tumor genes are mutated, including von Hippel-Lindau disease (OMIM 193300), adenomatous polyposis coli (OMIM 175100), tuberous sclerosis (OMIM 191100) and Birt-Hogg-Dubé syndrome (OMIM 135150). Timely diagnosis of these syndromes is essential for entry into appropriate screening protocols, which have been shown to effectively prolong life expectancy in these cohorts of patients. PMID:27625869

Chronic kidney disease guideline implementation in primary care: a qualitative report from the TRANSLATE CKD study

PubMed Central

Vest, Bonnie M.; York, Trevor R.M.; Sand, Jessica; Fox, Chester H.; Kahn, Linda S.

2016-01-01

Background Primary care physicians (PCPs) are optimally situated to identify and manage early-stage chronic kidney disease (CKD). Nonetheless, studies have documented suboptimal PCP understanding, awareness, and management of early CKD. The TRANSLATE CKD study is an ongoing national mixed-methods cluster randomized control trial that examines the implementation of evidence-based guidelines for CKD into primary care practice. Methods As part of mixed-methods process evaluation, semi-structured interviews were conducted by phone with 27 providers participating in the study. Interviews were audio-taped and transcribed. Thematic content analysis was used to identify themes. Themes were categorized according to the four domains of Normalization Process Theory (NPT). Results Identified themes illuminated the complex work undertaken in primary care practices to manage CKD. Barriers to guideline implementation were identified in each of the four NPT domains, including: 1) lack of knowledge and understanding around CKD (coherence), 2) difficulties engaging providers and patients in CKD management (cognitive participation), 3) limited time and competing demands (collective action), and 4) challenges obtaining and utilizing data to monitor progress (reflexive monitoring). Conclusions Addressing the barriers to implementation with concrete interventions at the levels at which they occur, informed by NPT, will ultimately improve the quality of CKD patient care. PMID:26355134

Chronic Kidney Disease Guideline Implementation in Primary Care: A Qualitative Report from the TRANSLATE CKD Study.

PubMed

Vest, Bonnie M; York, Trevor R M; Sand, Jessica; Fox, Chester H; Kahn, Linda S

2015-01-01

Primary care physicians (PCPs) are optimally situated to identify and manage early stage chronic kidney disease (CKD). Nonetheless, studies have documented suboptimal PCP understanding, awareness, and management of early CKD. The TRANSLATE CKD study is an ongoing national, mixed-methods, cluster randomized control trial that examines the implementation of evidence-based guidelines for CKD into primary care practice. As part of the mixed-methods process evaluation, semistructured interviews were conducted by phone with 27 providers participating in the study. Interviews were audio-taped and transcribed. Thematic content analysis was used to identify themes. Themes were categorized according to the 4 domains of Normalization Process Theory (NPT). Identified themes illuminated the complex work undertaken to manage CKD in primary care practices. Barriers to guideline implementation were identified in each of the 4 NPT domains, including (1) lack of knowledge and understanding around CKD (coherence), (2) difficulties engaging providers and patients in CKD management (cognitive participation), (3) limited time and competing demands (collective action), and (4) challenges obtaining and using data to monitor progress (reflexive monitoring). Addressing the barriers to implementation with concrete interventions at the levels at which they occur, informed by NPT, will ultimately improve the quality of CKD patient care. © Copyright 2015 by the American Board of Family Medicine.

Disease modeling and drug screening for neurological diseases using human induced pluripotent stem cells.

PubMed

Xu, Xiao-hong; Zhong, Zhong

2013-06-01

With the general decline of pharmaceutical research productivity, there are concerns that many components of the drug discovery process need to be redesigned and optimized. For example, the human immortalized cell lines or animal primary cells commonly used in traditional drug screening may not faithfully recapitulate the pathological mechanisms of human diseases, leading to biases in assays, targets, or compounds that do not effectively address disease mechanisms. Recent advances in stem cell research, especially in the development of induced pluripotent stem cell (iPSC) technology, provide a new paradigm for drug screening by permitting the use of human cells with the same genetic makeup as the patients without the typical quantity constraints associated with patient primary cells. In this article, we will review the progress made to date on cellular disease models using human stem cells, with a focus on patient-specific iPSCs for neurological diseases. We will discuss the key challenges and the factors that associated with the success of using stem cell models for drug discovery through examples from monogenic diseases, diseases with various known genetic components, and complex diseases caused by a combination of genetic, environmental and other factors.

Molecular etiology of primary hyperoxaluria type 1: new directions for treatment.

PubMed

Danpure, Christopher J

2005-01-01

Primary hyperoxaluria type 1 (PH1) is a rare autosomal-recessive disorder caused by a deficiency of the liver-specific enzyme alanine:glyoxylate aminotransferase (AGT). AGT deficiency results in increased synthesis and excretion of the metabolic end-product oxalate and deposition of insoluble calcium oxalate in the kidney and urinary tract. Classic treatments for PH1 have tended to address the more distal aspects of the disease process (i.e. the symptoms rather than the causes). However, advances in the understanding of the molecular etiology of PH1 over the past decade have shifted attention towards the more proximal aspects of the disease process (i.e. the causes rather than the symptoms). The determination of the crystal structure of AGT has enabled the effects of some of the most important missense mutations in the AGXT gene to be rationalised in terms of AGT folding, dimerization and stability. This has opened up new possibilities for the design pharmacological agents that might counteract the destabilizing effects of these mutations and which might be of use for the treatment of a potentially life-threatening and difficult-to-treat disease.

Forest health in the Blue Mountains: an plant ecologist's perspective on ecosystem processes and biological diversity.

Treesearch

Charles G. Johnson

1994-01-01

Natural disturbances are important to ecosystem processes. Disturbances historically have occurred in the vegetation of the Blue Mountain area of northeastern Oregon and southeastern Washington. The primary modifying events that historically have cycled through most of its plant communities are fire, grazing and browsing, insect and disease epidemics, windthrow,...

Understanding the management of early-stage chronic kidney disease in primary care: a qualitative study

PubMed Central

Blakeman, Tom; Protheroe, Joanne; Chew-Graham, Carolyn; Rogers, Anne; Kennedy, Anne

2012-01-01

Background Primary care is recognised to have an important role in the delivery of care for people with chronic kidney disease (CKD). However, there is evidence that CKD management is currently suboptimal, with a range of practitioner concerns about its management. Aim To explore processes underpinning the implementation of CKD management in primary care. Design and setting Qualitative study in general practices participating in a chronic kidney disease collaborative undertaken as part of the National Institute for Health Research (NIHR) Collaboration for Leadership in Applied Health Research and Care (CLAHRC) for Greater Manchester. Method Semi-structured interviews were conducted with GPs and practice nurses (n = 21). Normalisation Process Theory provided a framework for generation and analysis of the data. Results A predominant theme was anxiety about the disclosure of early-stage CKD with patients. The tensions experienced related to identifying and discussing CKD in older people and patients with stage 3A, embedding early-stage CKD within vascular care, and the distribution of work within the practice team. Participants provided accounts of work undertaken to resolve the difficulties encountered, with efforts having tended to focus on reassuring patients. Analysis also highlighted how anxiety surrounding disclosure influenced, and was shaped by, the organisation of care for people with CKD and associated long-term conditions. Conclusion Offering reassurance alone may be of limited benefit, and current management of early-stage CKD in primary care may miss opportunities to address susceptibility to kidney injury, improve self-management of vascular conditions, and improve the management of multimorbidity. PMID:22520910

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.

Specialized nursing practice for chronic disease management in the primary care setting: an evidence-based analysis.

PubMed

2013-01-01

In response to the increasing demand for better chronic disease management and improved health care efficiency in Ontario, nursing roles have expanded in the primary health care setting. To determine the effectiveness of specialized nurses who have a clinical role in patient care in optimizing chronic disease management among adults in the primary health care setting. A literature search was performed using OVID MEDLINE, OVID MEDLINE In-Process and Other Non-Indexed Citations, OVID EMBASE, EBSCO Cumulative Index to Nursing & Allied Health Literature (CINAHL), the Wiley Cochrane Library, and the Centre for Reviews and Dissemination database. Results were limited to randomized controlled trials and systematic reviews and were divided into 2 models: Model 1 (nurse alone versus physician alone) and Model 2 (nurse and physician versus physician alone). Effectiveness was determined by comparable outcomes between groups in Model 1, or improved outcomes or efficiency in Model 2. Six studies were included. In Model 1, there were no significant differences in health resource use, disease-specific measures, quality of life, or patient satisfaction. In Model 2, there was a reduction in hospitalizations and improved management of blood pressure and lipids among patients with coronary artery disease. Among patients with diabetes, there was a reduction in hemoglobin A1c but no difference in other disease-specific measures. There was a trend toward improved process measures, including medication prescribing and clinical assessments. Results related to quality of life were inconsistent, but patient satisfaction with the nurse-physician team was improved. Overall, there were more and longer visits to the nurse, and physician workload did not change. There was heterogeneity across patient populations, and in the titles, roles, and scope of practice of the specialized nurses. Specialized nurses with an autonomous role in patient care had comparable outcomes to physicians alone (Model 1) based on moderate quality evidence, with consistent results among a subgroup analysis of patients with diabetes based on low quality evidence. Model 2 showed an overall improvement in appropriate process measures, disease-specific measures, and patient satisfaction based on low to moderate quality evidence. There was low quality evidence that nurses working under Model 2 may reduce hospitalizations for patients with coronary artery disease. The specific role of the nurse in supplementing or substituting physician care was unclear, making it difficult to determine the impact on efficiency. Nurses with additional skills, training, or scope of practice may help improve the primary care of patients with chronic diseases. This review found that specialized nurses working on their own could achieve health outcomes that were similar to those of doctors. It also found that specialized nurses who worked with doctors could reduce hospital visits and improve certain patient outcomes related to diabetes, coronary artery disease, or heart failure. Patients who had nurse-led care were more satisfied and tended to receive more tests and medications. It is unclear whether specialized nurses improve quality of life or doctor workload.

Prevalence of chronic diseases by immigrant status and disparities in chronic disease management in immigrants: a population-based cohort study, Valore Project.

PubMed

Buja, Alessandra; Gini, Rosa; Visca, Modesta; Damiani, Gianfranco; Federico, Bruno; Francesconi, Paolo; Donato, Daniele; Marini, Alessandro; Donatini, Andrea; Brugaletta, Salvatore; Baldo, Vincenzo; Bellentani, Mariadonata

2013-05-24

For chronic conditions, disparities can take effect cumulatively at various times as the disease progresses, even when care is provided. The aim of this study was to quantify the prevalence of diabetes, congestive heart failure (CHF) and coronary heart disease (CHD) in adults by citizenship, and to compare the performance of primary care services in managing these chronic conditions, again by citizenship. This is a population-based retrospective cohort study on 1,948,622 people aged 16 years or more residing in Italy. A multilevel regression model was applied to analyze adherence to care processes using explanatory variables at both patient and district level. The age-adjusted prevalence of diabetes was found higher among immigrants from high migratory pressure countries (HMPC) than among Italians, while the age-adjusted prevalence of CHD and CHF was higher for Italians than for HMPC immigrants or those from highly-developed countries (HDC). Our results indicate lower levels in all quality management indicators for citizens from HMPC than for Italians, for all the chronic conditions considered. Patients from HDC did not differ from Italian in their adherence to disease management schemes. This study revealed a different prevalence of chronic diseases by citizenship, implying a different burden of primary care by citizenship. Our findings show that more effort is needed to guarantee migrant-sensitive primary health care.

Are Anxiety and Depression Addressed in Primary Care Patients With Chronic Obstructive Pulmonary Disease? A Chart Review

PubMed Central

Roundy, Kent; Cully, Jeffrey A.; Stanley, Melinda A.; Veazey, Connie; Souchek, Julianne; Wray, Nelda P.; Kunik, Mark E.

2005-01-01

Objective: Screening for mental illness in primary care is widely recommended, but little is known about the evaluation, treatment, and long-term management processes that follow screening. The aim of this study was to examine and describe the quality of mental health care for persons with chronic obstructive pulmonary disease (COPD) and anxiety/depressive disorders, as measured by adherence to practice guidelines. Method: This retrospective chart review examined data for 102 primary care and mental health care patients with COPD who were diagnosed, using Structured Clinical Interview for DSM-IV criteria, with major depressive disorder, dysthymia, depression not otherwise specified, generalized anxiety disorder, or anxiety not otherwise specified. Data were gathered from primary care progress notes from the year prior to enrollment in a randomized controlled trial (enrollment was from July 2002 to April 2004). We compared the care received by these patients over 1 year with that recommended by practice guidelines. Charts were abstracted using a checklist of recommended practice guidelines for diagnostic evaluation, acute treatment, and long-term management of anxiety and depressive disorders. Results: Fifty (49%) of the 102 patients were recognized during the review year as having an anxiety or depressive disorder. Eighteen patients were newly assessed for depressive or anxiety disorders during the chart review year. Patients followed in primary care alone, compared with those who were comanaged by mental health care providers, were less likely to have guideline-adherent care. Conclusion: Depressive and anxiety disorders are recognized in about half of patients; however, guideline-supported diagnostic evaluation, acute treatment (except for medications), and long-term management rarely occur in the primary care setting. To improve the treatment of depressive and anxiety disorders in primary care, the process of care delivery must be understood and changed. PMID:16308576

Study protocol of EMPOWER participatory action research (EMPOWER-PAR): a pragmatic cluster randomised controlled trial of multifaceted chronic disease management strategies to improve diabetes and hypertension outcomes in primary care.

PubMed

Ramli, Anis S; Lakshmanan, Sharmila; Haniff, Jamaiyah; Selvarajah, Sharmini; Tong, Seng F; Bujang, Mohamad-Adam; Abdul-Razak, Suraya; Shafie, Asrul A; Lee, Verna K M; Abdul-Rahman, Thuhairah H; Daud, Maryam H; Ng, Kien K; Ariffin, Farnaza; Abdul-Hamid, Hasidah; Mazapuspavina, Md-Yasin; Mat-Nasir, Nafiza; Miskan, Maizatullifah; Stanley-Ponniah, Jaya P; Ismail, Mastura; Chan, Chun W; Abdul-Rahman, Yong R; Chew, Boon-How; Low, Wilson H H

2014-09-13

Chronic disease management presents enormous challenges to the primary care workforce because of the rising epidemic of cardiovascular risk factors. The chronic care model was proven effective in improving chronic disease outcomes in developed countries, but there is little evidence of its effectiveness in developing countries. The aim of this study was to evaluate the effectiveness of the EMPOWER-PAR intervention (multifaceted chronic disease management strategies based on the chronic care model) in improving outcomes for type 2 diabetes mellitus and hypertension using readily available resources in the Malaysian public primary care setting. This paper presents the study protocol. A pragmatic cluster randomised controlled trial using participatory action research is underway in 10 public primary care clinics in Selangor and Kuala Lumpur, Malaysia. Five clinics were randomly selected to provide the EMPOWER-PAR intervention for 1 year and another five clinics continued with usual care. Each clinic consecutively recruits type 2 diabetes mellitus and hypertension patients fulfilling the inclusion and exclusion criteria over a 2-week period. The EMPOWER-PAR intervention consists of creating/strengthening a multidisciplinary chronic disease management team, training the team to use the Global Cardiovascular Risks Self-Management Booklet to support patient care and reinforcing the use of relevant clinical practice guidelines for management and prescribing. For type 2 diabetes mellitus, the primary outcome is the change in the proportion of patients achieving HbA1c < 6.5%. For hypertension without type 2 diabetes mellitus, the primary outcome is the change in the proportion of patients achieving blood pressure < 140/90 mmHg. Secondary outcomes include the proportion of patients achieving targets for serum lipid profile, body mass index and waist circumference. Other outcome measures include medication adherence levels, process of care and prescribing patterns. Patients' assessment of their chronic disease care and providers' perceptions, attitudes and perceived barriers in care delivery and cost-effectiveness of the intervention are also evaluated. Results from this study will provide objective evidence of the effectiveness and cost-effectiveness of a multifaceted intervention based on the chronic care model in resource-constrained public primary care settings. The evidence should instigate crucial primary care system change in Malaysia. ClinicalTrials.gov NCT01545401.

Jaundice in primary care: a cohort study of adults aged >45 years using electronic medical records.

PubMed

Taylor, Anna; Stapley, Sally; Hamilton, William

2012-08-01

Jaundice is a rare but important symptom of malignant and benign conditions. When patients present in primary care, understanding the relative likelihood of different disease processes can help GPs to investigate and refer patients appropriately. To identify and quantify the various causes of jaundice in adults presenting in primary care. Historical cohort study using electronic primary care records. UK General Practice Research Database. Participants (186 814 men and women) aged >45 years with clinical events recorded in primary care records between 1 January 2005 and 31 December 2007. Data were searched for episodes of jaundice and explanatory diagnoses identified within the subsequent 12 months. If no diagnosis was found, the patient's preceding medical record was searched for relevant chronic diseases. From the full cohort, 277 patients had at least one record of jaundice between 1 January 2005 and 31 December 2006. Ninety-two (33%) were found to have bile duct stones; 74 (27%) had an explanatory cancer [pancreatic cancer 34 (12%), cholangiocarcinoma 13 (5%) and other diagnosed primary malignancy 27 (10%)]. Liver disease attributed to excess alcohol explained 26 (9%) and other diagnoses were identified in 24 (9%). Sixty-one (22%) had no diagnosis related to jaundice recorded. Although the most common cause of jaundice is bile duct stones, cancers are present in over a quarter of patients with jaundice in this study, demonstrating the importance of urgent investigation into the underlying cause.

[Meanings and methods of territorialization in primary health care].

PubMed

Pessoa, Vanira Matos; Rigotto, Raquel Maria; Carneiro, Fernando Ferreira; Teixeira, Ana Cláudia de Araújo

2013-08-01

Territorially-based participative analytical methodologies taking the environmental question and work into consideration are essential for effective primary health care. The study analyzed work and environment-related processes in the primary health care area and their repercussions on the health of workers and the community in a rural city in Ceará, whose economy is based on agriculture for export,. It sought to redeem the area and the proposal of actions focused on health needs by the social subjects through the making of social, environmental and work-related maps in workshops within the framework of action research. Examining the situation from a critical perspective, based on social participation and social determination of the health-disease process with regard to the relations between production, environment and health, was the most important step in the participative map-making process, with the qualitative material interpreted in light of discourse analysis. The process helped identify the health needs, the redemption of the area, strengthened the cooperation between sectors and the tie between the health of the worker and that of the environment, and represented an advance towards the eradication of the causes of poor primary health care services.

Auditory processing deficits in individuals with primary open-angle glaucoma.

PubMed

Rance, Gary; O'Hare, Fleur; O'Leary, Stephen; Starr, Arnold; Ly, Anna; Cheng, Belinda; Tomlin, Dani; Graydon, Kelley; Chisari, Donella; Trounce, Ian; Crowston, Jonathan

2012-01-01

The high energy demand of the auditory and visual pathways render these sensory systems prone to diseases that impair mitochondrial function. Primary open-angle glaucoma, a neurodegenerative disease of the optic nerve, has recently been associated with a spectrum of mitochondrial abnormalities. This study sought to investigate auditory processing in individuals with open-angle glaucoma. DESIGN/STUDY SAMPLE: Twenty-seven subjects with open-angle glaucoma underwent electrophysiologic (auditory brainstem response), auditory temporal processing (amplitude modulation detection), and speech perception (monosyllabic words in quiet and background noise) assessment in each ear. A cohort of age, gender and hearing level matched control subjects was also tested. While the majority of glaucoma subjects in this study demonstrated normal auditory function, there were a significant number (6/27 subjects, 22%) who showed abnormal auditory brainstem responses and impaired auditory perception in one or both ears. The finding that a significant proportion of subjects with open-angle glaucoma presented with auditory dysfunction provides evidence of systemic neuronal susceptibility. Affected individuals may suffer significant communication difficulties in everyday listening situations.

Quality of cardiovascular disease care in Ontario's primary care practices: a cross sectional study examining differences in guideline adherence by patient sex.

PubMed

Naicker, Kiyuri; Liddy, Clare; Singh, Jatinderpreet; Taljaard, Monica; Hogg, William

2014-06-18

Women are disproportionately affected by cardiovascular disease, often experiencing poorer outcomes following a cardiovascular event. Evidence points to inequities in processes of care as a potential contributing factor. This study sought to determine whether any sex differences exist in adherence to process of care guidelines for cardiovascular disease within primary care practices in Ontario, Canada. This is a secondary analysis of pooled cross-sectional baseline data collected through a larger quality improvement initiative known as the Improved Delivery of Cardiovascular Care (IDOCC). Chart abstraction was performed for 4,931 patients from 84 primary care practices in Eastern Ontario who had, or were at high risk of, cardiovascular disease. Measures examining adherence to guidelines associated with nine areas of cardiovascular care (coronary artery disease, peripheral vascular disease (PVD), stroke/transient ischemic attack, chronic kidney disease, diabetes, dyslipidemia, hypertension, smoking cessation, and weight management) were collected. Multivariable logistic regression analysis was performed to evaluate sex differences, adjusting for age, physician remuneration, and rurality. Women were significantly less likely to have their lipid profiles taken (OR=1.17, 95% CI 1.03-1.33), be prescribed lipid lowering medication for dyslipidemia (OR=1.54, 95% CI 1.20-1.97), and to be prescribed ASA following stroke (OR=1.56, 95% CI 1.39-1.75). Women with PVD were significantly less likely to be prescribed ACE inhibitors and/or angiotensin receptor blockers (OR=1.74, 95% CI 1.25-2.41) and lipid lowering medications (OR=1.95, 95% CI 1.46-2.62) or ASA (OR=1.59, 95% CI 1.43-1.78). However, women were more likely to have two blood pressure measurements taken and to be referred to a dietician or weight loss program. Male patients with diabetes were less likely to be prescribed glycemic control medication (OR=0.84, 95% CI 0.74-0.86). Sex disparities exist in the quality of cardiovascular care in Canadian primary care practices, which tend to favour men. Women with PVD have a particularly high risk of not receiving appropriate medications. Our findings indicate that improvements in care delivery should be made to address these issues, particularly with regard to the prescribing of recommended medications for women, and preventive measures for men.

The IL-6 response to Chlamydia from primary reproductive epithelial cells is highly variable and may be involved in differential susceptibility to the immunopathological consequences of chlamydial infection

PubMed Central

2013-01-01

Background Chlamydia trachomatis infection results in reproductive damage in some women. The process and factors involved in this immunopathology are not well understood. This study aimed to investigate the role of primary human cellular responses to chlamydial stress response proteases and chlamydial infection to further identify the immune processes involved in serious disease sequelae. Results Laboratory cell cultures and primary human reproductive epithelial cultures produced IL-6 in response to chlamydial stress response proteases (CtHtrA and CtTsp), UV inactivated Chlamydia, and live Chlamydia. The magnitude of the IL-6 response varied considerably (up to 1000 pg ml-1) across different primary human reproductive cultures. Thus different levels of IL-6 production by reproductive epithelia may be a determinant in disease outcome. Interestingly, co-culture models with either THP-1 cells or autologous primary human PBMC generally resulted in increased levels of IL-6, except in the case of live Chlamydia where the level of IL-6 was decreased compared to the epithelial cell culture only, suggesting this pathway may be able to be modulated by live Chlamydia. PBMC responses to the stress response proteases (CtTsp and CtHtrA) did not significantly vary for the different participant cohorts. Therefore, these proteases may possess conserved innate PAMPs. MAP kinases appeared to be involved in this IL-6 induction from human cells. Finally, we also demonstrated that IL-6 was induced by these proteins and Chlamydia from mouse primary reproductive cell cultures (BALB/C mice) and mouse laboratory cell models. Conclusions We have demonstrated that IL-6 may be a key factor for the chlamydial disease outcome in humans, given that primary human reproductive epithelial cell culture showed considerable variation in IL-6 response to Chlamydia or chlamydial proteins, and that the presence of live Chlamydia (but not UV killed) during co-culture resulted in a reduced IL-6 response suggesting this response may be moderated by the presence of the organism. PMID:24238294

High resolution neurography of the lumbosacral plexus on 3T magneteic resonance imaging.

PubMed

Cejas, C; Escobar, I; Serra, M; Barroso, F

2015-01-01

Magnetic resonance neurography is a technique that complements clinical and electrophysiological study of the peripheral nerves and brachial and lumbosacral plexuses. Numerous focal processes (inflammatory, traumatic, primary tumors, secondary tumors) and diffuse processes (diabetic polyneuropathy, chronic idiopathic demyelinating polyneuropathy due to amyloidosis or Charcot-Marie-Tooth disease) can involve the lumbosacral plexus. This article reviews the anatomy of the lumbosacral plexus, describes the technique for neurography of the plexus at our institution, and shows the diverse diseases that affect it. Copyright © 2014 SERAM. Published by Elsevier España, S.L.U. All rights reserved.

A framework for physician assistant intervention for overweight and obesity.

PubMed

Herman, Lawrence; McGinnity, John G; Doll, Michael; Peterson, Eric D; Russell, Amanda; Largay, Joseph

2015-07-01

Overweight and obesity compose a chronic disease process of epidemic proportions that presents on a continuum, likely affecting nearly two out of every three patients treated by physician assistants (PAs). However, meaningful and actionable definitions, including but not limited to anthropometric and clinical descriptors, are needed. The effective treatment of overweight and obesity requires an efficient and timely process of screening, diagnosis, evaluation of complications, staging, and clear algorithmic management. PAs are trained as primary care providers and can diagnose and treat overweight and obese patients regardless of practice setting and across the spectrum of the disease and patient's age.

Primary care nurses' communication and its influence on patient talk during motivational interviewing.

PubMed

Östlund, Ann-Sofi; Wadensten, Barbro; Häggström, Elisabeth; Lindqvist, Helena; Kristofferzon, Marja-Leena

2016-11-01

The aim of this study was to describe what verbal behaviours/kinds of talk occur during recorded motivational interviewing sessions between nurses in primary care and their patients. The aim was also to examine what kinds of nurse talk predict patient change talk, neutral talk and/or sustain talk. Motivational interviewing is a collaborative conversational style. It has been shown to be effective, in addressing health behaviours such as diet, exercise, weight loss and chronic disease management. In Sweden, it is one of the approaches to disease prevention conversations with patients recommended in the National Guidelines for Disease Prevention. Research on the mechanisms underlying motivational interviewing is growing, but research on motivational interviewing and disease prevention has also been called for. A descriptive and predictive design was used. Data were collected during 2011-2014. Fifty audio-recorded motivational interviewing sessions between 23 primary care nurses and 50 patients were analysed using Motivational Interviewing Sequential Code for Observing Process Exchanges. The frequency of specific kinds of talk and sequential analysis (to predict patient talk from nurse talk) were computed using the software Generalized Sequential Querier 5. The primary care nurses and patients used neutral talk most frequently. Open and negative questions, complex and positive reflections were significantly more likely to be followed by change talk and motivational interviewing-inconsistent talk, positive questions and negative reflections by sustain talk. To increase patients' change talk, primary care nurses need to use more open questions, complex reflections and questions and reflections directed towards change. © 2016 John Wiley & Sons Ltd.

[Epidemiology, risk factors and molecular pathogenesis of primary liver cancer].

PubMed

Hagymási, Krisztina; Tulassay, Zsolt

2008-03-23

Primary liver cancer is the fifth most common cancer worldwide. Hepatocellular carcinoma accounts for 85-90% of primary liver cancers. Distribution of hepatocellular carcinoma shows variations among geographic regions and ethnic groups. Males have higher liver cancer rates than females. Hepatocellular carcinoma occurs within an established background of chronic liver disease and cirrhosis (70-90%). Major causes (80%) of hepatocellular carcinoma are hepatitis B, C virus infection, and aflatoxin exposition. Its development is a multistep process. We have a growing understanding on the molecular pathogenesis. Genetic and epigenetic changes activate oncogenes, inhibit tumorsuppressor genes, which result in autonomous cell proliferation. The chromosomal instability caused by telomere dysfunction, the growth-retrained environment and the alterations of the micro- and macroenvironment help the expansion of the malignant cells. Understanding the molecular mechanisms could improve the screening of patients with chronic liver disease, or cirrhosis, and the prevention as well as treatment of hepatocellular carcinoma.

Alzheimer Disease and Its Growing Epidemic: Risk Factors, Biomarkers, and the Urgent Need for Therapeutics.

PubMed

Hickman, Richard A; Faustin, Arline; Wisniewski, Thomas

2016-11-01

Alzheimer disease (AD) represents one of the greatest medical challenges of this century; the condition is becoming increasingly prevalent worldwide and no effective treatments have been developed for this terminal disease. Because the disease manifests at a late stage after a long period of clinically silent neurodegeneration, knowledge of the modifiable risk factors and the implementation of biomarkers is crucial in the primary prevention of the disease and presymptomatic detection of AD, respectively. This article discusses the growing epidemic of AD and antecedent risk factors in the disease process. Disease biomarkers are discussed, and the implications that this may have for the treatment of this currently incurable disease. Copyright © 2016 Elsevier Inc. All rights reserved.

Disease diagnosis in primary care in Uganda.

PubMed

Mbonye, Martin Kayitale; Burnett, Sarah M; Colebunders, Robert; Naikoba, Sarah; Van Geertruyden, Jean-Pierre; Weaver, Marcia R; Ronald, Allan

2014-10-08

The overall burden of disease (BOD) especially for infectious diseases is higher in Sub-Saharan Africa than other regions of the world. Existing data collected through the Health Management Information System (HMIS) may not be optimal to measure BOD. The Infectious Diseases Capacity Building Evaluation (IDCAP) cooperated with the Ugandan Ministry of Health to improve the quality of HMIS data. We describe diagnoses with associated clinical assessments and laboratory investigations of outpatients attending primary care in Uganda. IDCAP supported HMIS data collection at 36 health center IVs in Uganda for five months (November 2009 to March 2010) prior to implementation of the IDCAP interventions. Descriptive analyses were performed on a cross-sectional dataset of 209,734 outpatient visits during this period. Over 500 illnesses were diagnosed. Infectious diseases accounted for 76.3% of these and over 30% of visits resulted in multiple diagnoses. Malaria (48.3%), cough/cold (19.4%), and intestinal worms (6.6%) were the most frequently diagnosed illnesses. Body weight was recorded for 36.8% of patients and less than 10% had other clinical assessments recorded. Malaria smears (64.2%) and HIV tests (12.2%) accounted for the majority of 84,638 laboratory tests ordered. Fewer than 30% of patients for whom a laboratory investigation was available to confirm the clinical impression had the specific test performed. We observed a broad range of diagnoses, a high percentage of multiple diagnoses including true co-morbidities, and underutilization of laboratory support. This emphasizes the complexity of illnesses to be addressed by primary healthcare workers. An improved HMIS collecting timely, quality data is needed. This would adequately describe the burden of disease and processes of care at primary care level, enable appropriate national guidelines, programs and policies and improve accountability for the quality of care.

Quality of Care for Patients with Chronic Respiratory Diseases: Data for Accreditation Plan in Primary Healthcare.

PubMed

Kurpas, Donata; Szwamel, Katarzyna; Mroczek, Bożena

There are scarce reports in the literature on factors affecting the assessment of the quality of care for patients with chronic respiratory diseases. Such information is relevant in the accreditation process on implementing the healthcare. The study group consisted of 133 adult patients with chronic respiratory diseases and 125 adult patients with chronic non-respiratory diseases. In the present study, the level of satisfaction from healthcare provided by the primary healthcare unit, disease acceptance, quality of life, health behaviors, and met needs were examined, as well as associations between variables with the use of correspondence analysis. The results are that in patients with chronic respiratory diseases an increase in satisfaction depends on the improvement of well-being in the mental sphere. The lack of problems with obtaining a referral to a specialist and a higher level of fulfilled needs also have a positive effect. Additionally, low levels of satisfaction should be expected in those patients with chronic respiratory diseases who wait for an appointment in front of the office for a long time, report problems with obtaining a referral to additional tests, present a low level of health behaviors, and have a low index of benefits.

Evaluation of the implementation of an integrated program for musculoskeletal system care.

PubMed

Larrañaga, Igor; Soto-Gordoa, Myriam; Arrospide, Arantzazu; Jauregi, María Luz; Millas, Jesús; San Vicente, Ricardo; Aguirrebeña, Jabier; Mar, Javier

The chronic nature of musculoskeletal diseases requires an integrated care which involves the Primary Care and the specialities of Rheumatology, Traumatology and Rehabilitation. The aim of this study was to assess the implementation of an integrated organizational model in osteoporosis, low back pain, shoulder disease and knee disease using Deming's continuous improvement process and considering referrals and resource consumption. A simulation model was used in the planning to predict the evolution of musculoskeletal diseases resource consumption and to carry out a Budget Impact Analysis from 2012 to 2020 in the Goierri-Alto Urola region. In the checking stage the status of the process in 2014 was evaluated using statistical analysis to check the degree of achievement of the objectives for each speciality. Simulation models showed that population with musculoskeletal disease in Goierri-Alto Urola will increase a 4.4% by 2020. Because of that, the expenses for a conventional healthcare system will have increased a 5.9%. However, if the intervention reaches its objectives the budget would decrease an 8.5%. The statistical analysis evidenced a decline in referrals to Traumatology service and a reduction of successive consultations in all specialities. The implementation of the integrated organizational model in osteoporosis, low back pain, shoulder disease and knee disease is still at an early stage. However, the empowerment of Primary Care improved patient referrals and reduced the costs. Copyright © 2016 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

Implementation of the BETTER 2 program: a qualitative study exploring barriers and facilitators of a novel way to improve chronic disease prevention and screening in primary care.

PubMed

Sopcak, Nicolette; Aguilar, Carolina; O'Brien, Mary Ann; Nykiforuk, Candace; Aubrey-Bassler, Kris; Cullen, Richard; Grunfeld, Eva; Manca, Donna Patricia

2016-12-01

BETTER (Building on Existing Tools to Improve Chronic Disease Prevention and Screening in Primary Care) is a patient-based intervention to improve chronic disease prevention and screening (CDPS) for cardiovascular disease, diabetes, cancer, and associated lifestyle factors in patients aged 40 to 65. The key component of BETTER is a prevention practitioner (PP), a health care professional with specialized skills in CDPS who meets with patients to develop a personalized prevention prescription, using the BETTER toolkit and Brief Action Planning. The purpose of this qualitative study was to understand facilitators and barriers of the implementation of the BETTER 2 program among clinicians, patients, and stakeholders in three (urban, rural, and remote) primary care settings in Newfoundland and Labrador, Canada. We collected and analyzed responses from 20 key informant interviews and 5 focus groups, as well as memos and field notes. Data were organized using Nvivo 10 software and coded using constant comparison methods. We then employed the Consolidated Framework for Implementation Research (CFIR) to focus our analysis on the domains most relevant for program implementation. The following key elements, within the five CFIR domains, were identified as impacting the implementation of BETTER 2: (1) intervention characteristics-complexity and cost of the intervention; (2) outer setting-perception of fit including lack of remuneration, lack of resources, and duplication of services, as well as patients' needs as perceived by physicians and patients; (3) characteristics of prevention practitioners-interest in prevention and ability to support and motivate patients; (4) inner setting-the availability of a local champion and working in a team versus working as a team; and (5) process-planning and engaging, collaboration, and teamwork. The implementation of a novel CDPS program into new primary care settings is a complex, multi-level process. This study identified key elements that hindered or facilitated the implementation of the BETTER approach in three primary care settings in Newfoundland and Labrador. Employing the CFIR as an overarching typology allows for comparisons with other contexts and settings, and may be useful for practices, researchers, and policy-makers interested in the implementation of CDPS programs.

Recapitulating cortical development with organoid culture in vitro and modeling abnormal spindle-like (ASPM related primary) microcephaly disease.

PubMed

Li, Rui; Sun, Le; Fang, Ai; Li, Peng; Wu, Qian; Wang, Xiaoqun

2017-11-01

The development of a cerebral organoid culture in vitro offers an opportunity to generate human brain-like organs to investigate mechanisms of human disease that are specific to the neurogenesis of radial glial (RG) and outer radial glial (oRG) cells in the ventricular zone (VZ) and subventricular zone (SVZ) of the developing neocortex. Modeling neuronal progenitors and the organization that produces mature subcortical neuron subtypes during early stages of development is essential for studying human brain developmental diseases. Several previous efforts have shown to grow neural organoid in culture dishes successfully, however we demonstrate a new paradigm that recapitulates neocortical development process with VZ, OSVZ formation and the lamination organization of cortical layer structure. In addition, using patient-specific induced pluripotent stem cells (iPSCs) with dysfunction of the Aspm gene from a primary microcephaly patient, we demonstrate neurogenesis defects result in defective neuronal activity in patient organoids, suggesting a new strategy to study human developmental diseases in central nerve system.

Effectiveness of computerized clinical decision support systems for asthma and chronic obstructive pulmonary disease in primary care: a systematic review.

PubMed

Fathima, Mariam; Peiris, David; Naik-Panvelkar, Pradnya; Saini, Bandana; Armour, Carol Lyn

2014-12-02

The use of computerized clinical decision support systems may improve the diagnosis and ongoing management of chronic diseases, which requires recurrent visits to multiple health professionals, disease and medication monitoring and modification of patient behavior. The aim of this review was to systematically review randomized controlled trials evaluating the effectiveness of computerized clinical decision systems (CCDSS) in the care of people with asthma and COPD. Randomized controlled trials published between 2003 and 2013 were searched using multiple electronic databases Medline, EMBASE, CINAHL, IPA, Informit, PsychINFO, Compendex, and Cochrane Clinical Controlled Trials Register databases. To be included, RCTs had to evaluate the role of the CCDSSs for asthma and/or COPD in primary care. Nineteen studies representing 16 RCTs met our inclusion criteria. The majority of the trials were conducted in patients with asthma. Study quality was generally high. Meta-analysis was not conducted because of methodological and clinical heterogeneity. The use of CCDSS improved asthma and COPD care in 14 of the 19 studies reviewed (74%). Nine of the nineteen studies showed statistically significant (p < 0.05) improvement in the primary outcomes measured. The majority of the studies evaluated health care process measures as their primary outcomes (10/19). Evidence supports the effectiveness of CCDSS in the care of people with asthma. However there is very little information of its use in COPD care. Although there is considerable improvement in the health care process measures and clinical outcomes through the use of CCDSSs, its effects on user workload and efficiency, safety, costs of care, provider and patient satisfaction remain understudied.

Inflammation in sickle cell disease.

PubMed

Conran, Nicola; Belcher, John D

2018-01-01

The primary β-globin gene mutation that causes sickle cell disease (SCD) has significant pathophysiological consequences that result in hemolytic events and the induction of the inflammatory processes that ultimately lead to vaso-occlusion. In addition to their role in the initiation of the acute painful vaso-occlusive episodes that are characteristic of SCD, inflammatory processes are also key components of many of the complications of the disease including autosplenectomy, acute chest syndrome, pulmonary hypertension, leg ulcers, nephropathy and stroke. We, herein, discuss the events that trigger inflammation in the disease, as well as the mechanisms, inflammatory molecules and cells that propagate these inflammatory processes. Given the central role that inflammation plays in SCD pathophysiology, many of the therapeutic approaches currently under pre-clinical and clinical development for the treatment of SCD endeavor to counter aspects or specific molecules of these inflammatory processes and it is possible that, in the future, we will see anti-inflammatory drugs being used either together with, or in place of, hydroxyurea in those SCD patients for whom hematopoietic stem cell transplants and evolving gene therapies are not a viable option.

Demyelination of vestibular nerve axons in unilateral Ménière's disease.

PubMed

Spencer, Robert F; Sismanis, Aristides; Kilpatrick, Jefferson K; Shaia, Wayne T

2002-11-01

We conducted a study to determine whether vestibular nerves in patients with unilateral Ménière's disease whose symptoms are refractory to medical management exhibit neuropathologic changes. We also endeavored to determine whether retrocochlear abnormalities are primary or secondary factors in the disease process. To these ends, we obtained vestibular nerve segments from five patients during retrosigmoid (posterior fossa) neurectomy, immediately fixed them, and processed them for light and electron microscopy. We found that all five segments exhibited moderate to severe demyelination with axonal sparing. Moreover, we noted that reactive astrocytes produced an extensive proliferation of fibrous processes and that the microglia assumed a phagocytic role. We conclude that the possible etiologies of demyelination include viral and/or immune-mediated factors similar to those seen in other demyelinating diseases, such as multiple sclerosis and Guillain-Barré syndrome. Our findings suggest that some forms of Ménière's disease that are refractory to traditional medical management might be the result of retrocochlear pathology that affects the neuroglial portion of the vestibular nerve.

Comprehension of concrete and abstract words in semantic variant primary progressive aphasia and Alzheimer's disease: A behavioral and neuroimaging study.

PubMed

Joubert, Sven; Vallet, Guillaume T; Montembeault, Maxime; Boukadi, Mariem; Wilson, Maximiliano A; Laforce, Robert Jr; Rouleau, Isabelle; Brambati, Simona M

2017-07-01

The aim of this study was to investigate the comprehension of concrete, abstract and abstract emotional words in semantic variant primary progressive aphasia (svPPA), Alzheimer's disease (AD), and healthy elderly adults (HE) Three groups of participants (9 svPPA, 12 AD, 11 HE) underwent a general neuropsychological assessment, a similarity judgment task, and structural brain MRI. The three types of words were processed similarly in the group of AD participants. In contrast, patients in the svPPA group were significantly more impaired at processing concrete words than abstract words, while comprehension of abstract emotional words was in between. VBM analyses showed that comprehension of concrete words relative to abstract words was significantly correlated with atrophy in the left anterior temporal lobe. These results support the view that concrete words are disproportionately impaired in svPPA, and that concrete and abstract words may rely upon partly dissociable brain regions. Copyright © 2017 Elsevier Inc. All rights reserved.

Tau and Amyloid-β Cerebrospinal Fluid Biomarkers have Differential Relationships with Cognition in Mild Cognitive Impairment.

PubMed

Malpas, Charles B; Saling, Michael M; Velakoulis, Dennis; Desmond, Patricia; O'Brien, Terence J

2015-01-01

Alzheimer's disease (AD) is characterized by two primary pathologies: tau-related neurofibrillary tangles and the extracellular accumulation of amyloid-β (Aβ). The development of these pathologies is topologically distinct early in the disease, with Aβ beginning to accumulate as a diffuse, neocortical pathology, while tau-related pathology begins to form in mesial temporal regions. This study investigated the hypothesis that, by virtue of this distinction, there exist preferential associations between the primary pathologies and aspects of the cognitive phenotype. We investigated the relationship between cerebrospinal fluid (CSF) biomarkers for tau and Aβ pathologies with neurocognitive measures in 191 patients with mild cognitive impairment (MCI). Participants completed cognitive tests of new learning, information processing speed, and working memory. Separate regression models were computed and then followed up with mediation analyses to examine the predictive status of CSF biomarkers. The effect of Aβ on learning was mediated by phospho-tau (p = 0.008). In contrast, Aβ had a direct effect on information processing speed that was not mediated by phospho-tau (p = 0.59). No predictors were significant for working memory. This study provided evidence for a differential relationship of Aβ and phospho-tau pathologies on the neurocognitive phenotype of MCI. This supports the proposition that these primary AD pathologies maximally affect different aspects of cognition, and has potential implications for cognitive assessments and the use of biomarkers in disease-modifyingtherapeutic trials.

Vitamin D deficiency: infertility and neurodevelopmental diseases (attention deficit hyperactivity disorder, autism, and schizophrenia).

PubMed

Berridge, Michael J

2018-02-01

The process of development depends on a number of signaling systems that regulates the progressive sequence of developmental events. Infertility and neurodevelopmental diseases, such as attention deficit hyperactivity disorder, autism spectrum disorders, and schizophrenia, are caused by specific alterations in these signaling processes. Calcium signaling plays a prominent role throughout development beginning at fertilization and continuing through early development, implantation, and organ differentiation such as heart and brain development. Vitamin D plays a major role in regulating these signaling processes that control development. There is an increase in infertility and an onset of neurodevelopmental diseases when vitamin D is deficient. The way in which vitamin D deficiency acts to alter development is a major feature of this review. One of the primary functions of vitamin D is to maintain the phenotypic stability of both the Ca 2+ and redox signaling pathways that play such a key role throughout development.

Nursing contributions to chronic disease management in primary care.

PubMed

Lukewich, Julia; Edge, Dana S; VanDenKerkhof, Elizabeth; Tranmer, Joan

2014-02-01

As the prevalence of chronic diseases continues to increase, emphasis is being placed on the development of primary care strategies that enhance healthcare delivery. Innovations include interprofessional healthcare teams and chronic disease management strategies. To determine the roles of nurses working in primary care settings in Ontario and the extent to which chronic disease management strategies have been implemented. We conducted a cross-sectional survey of a random sample of primary care nurses, including registered practical nurses, registered nurses, and nurse practitioners, in Ontario between May and July 2011. Nurses in primary care reported engaging in chronic disease management activities but to different extents depending on their regulatory designation (licensure category). Chronic disease management strategy implementation was not uniform across primary care practices where the nurses worked. There is the potential to optimize and standardize the nursing role within primary care and improve the implementation of chronic disease management strategies.

[Relaunching primary healthcaree].

PubMed

Marcolongo, Adriano; Talarico, Francesco

2014-01-01

The health environment today is characterized by diffuse inequalities, the emergence of chronic diseases, and the introduction of new technologies, all of which, together with other factors are leading to a healthcare system that is becoming increasingly less sustainable from a financial point of view. Primary healthcare, public health and hospitals should work together to define a comprehensive healthcare delivery model characterized by continuity of care, information and management. The proposed model of disease management, in particular of chronic diseases, must reorganize health services around the needs of citizens and the community and involve patients and their families in the disease management process, by promoting self-help groups and patient organizations that cooperate with health services. In order to put this change into effect, evidence-based medicine and evidence-based practice need to be adopted. From an organizational point of view, it will be important to change wage rules, so as to implement a new payment system based upon performance. In this new contest, physicians specialized in hygiene and public health can play an important role that includes leadership, governance and coordination. By integrating the concepts of accountability, community intervention and training, we can acquire the tools to change the current hospital-based system to a new model of primary healthcare that works together with the community to move the focus from healthcare provider to patient.

Management of postmenopausal osteoporosis for primary care.

PubMed

Miller, P; Lukert, B; Broy, S; Civitelli, R; Fleischmann, R; Gagel, R; Khosla, S; Lucas, M; Maricic, M; Pacifici, R; Recker, R; Sarran, H S; Short, B; Short, M J

1998-01-01

The shift in health care delivery from a subspecialty to primary care system has transferred the responsibility of preventing osteoporotic fractures from specialists in metabolic bone disease to the web of physicians--family practitioners, general internists, pediatricians, and gynecologists--who provide the bulk of primary care. The challenge for this group of physicians is to decrease the rising prevalence of osteoporotic hip and vertebral fractures while operating within the cost parameters. It is the goal of this brief summary to provide primary practitioners with focused guidelines for the management of postmenopausal osteoporosis based on new and exciting developments. Prevention and treatment will change rapidly over the next decade and these advances will require changes in these recommendations. We identified patients at risk for osteoporosis and provided indications for bone mass measurement, criteria for diagnosis of osteoporosis, therapeutic interventions, and biochemical markers of the disease. Prevention and treatment are discussed, including hormone replacement therapy and use of calcitonin, sodium fluoride, bisphosphonates, and serum estrogen receptor modulators. Postmenopausal osteoporosis should no longer be an accepted process of aging. It is both preventable and treatable. Primary care physicians must proactively prevent and treat osteoporosis in their daily practice, and combination therapies are suggested.

Comparison of Cerebrospinal Fluid Opening Pressure in Children With Demyelinating Disease to Children With Primary Intracranial Hypertension.

PubMed

Morgan-Followell, Bethanie; Aylward, Shawn C

2017-03-01

The authors aimed to compare the opening pressures of children with demyelinating disease to children with primary intracranial hypertension. Medical records were reviewed for a primary diagnosis of demyelinating disease, or primary intracranial hypertension. Diagnosis of demyelinating disease was made according to either the 2007 or 2012 International Pediatric Multiple Sclerosis Study Group criteria. Primary intracranial hypertension diagnosis was confirmed by presence of elevated opening pressure, normal cerebrospinal fluid composition and neuroimaging. The authors compared 14 children with demyelinating disease to children with primary intracranial hypertension in 1:1 and 1:2 fashions. There was a statistically significant higher BMI in the primary intracranial hypertension group compared to the demyelinating group ( P = .0203). The mean cerebrospinal fluid white blood cell count was higher in the demyelinating disease group compared to primary intracranial hypertension ( P = .0002). Among both comparisons, the cerebrospinal fluid opening pressure, glucose, protein and red blood cell counts in children with demyelinating disease were comparable to age- and sex-matched controls with primary intracranial hypertension.

Specialized Nursing Practice for Chronic Disease Management in the Primary Care Setting

PubMed Central

2013-01-01

Background In response to the increasing demand for better chronic disease management and improved health care efficiency in Ontario, nursing roles have expanded in the primary health care setting. Objectives To determine the effectiveness of specialized nurses who have a clinical role in patient care in optimizing chronic disease management among adults in the primary health care setting. Data Sources and Review Methods A literature search was performed using OVID MEDLINE, OVID MEDLINE In-Process and Other Non-Indexed Citations, OVID EMBASE, EBSCO Cumulative Index to Nursing & Allied Health Literature (CINAHL), the Wiley Cochrane Library, and the Centre for Reviews and Dissemination database. Results were limited to randomized controlled trials and systematic reviews and were divided into 2 models: Model 1 (nurse alone versus physician alone) and Model 2 (nurse and physician versus physician alone). Effectiveness was determined by comparable outcomes between groups in Model 1, or improved outcomes or efficiency in Model 2. Results Six studies were included. In Model 1, there were no significant differences in health resource use, disease-specific measures, quality of life, or patient satisfaction. In Model 2, there was a reduction in hospitalizations and improved management of blood pressure and lipids among patients with coronary artery disease. Among patients with diabetes, there was a reduction in hemoglobin A1c but no difference in other disease-specific measures. There was a trend toward improved process measures, including medication prescribing and clinical assessments. Results related to quality of life were inconsistent, but patient satisfaction with the nurse-physician team was improved. Overall, there were more and longer visits to the nurse, and physician workload did not change. Limitations There was heterogeneity across patient populations, and in the titles, roles, and scope of practice of the specialized nurses. Conclusions Specialized nurses with an autonomous role in patient care had comparable outcomes to physicians alone (Model 1) based on moderate quality evidence, with consistent results among a subgroup analysis of patients with diabetes based on low quality evidence. Model 2 showed an overall improvement in appropriate process measures, disease-specific measures, and patient satisfaction based on low to moderate quality evidence. There was low quality evidence that nurses working under Model 2 may reduce hospitalizations for patients with coronary artery disease. The specific role of the nurse in supplementing or substituting physician care was unclear, making it difficult to determine the impact on efficiency. Plain Language Summary Nurses with additional skills, training, or scope of practice may help improve the primary care of patients with chronic diseases. This review found that specialized nurses working on their own could achieve health outcomes that were similar to those of doctors. It also found that specialized nurses who worked with doctors could reduce hospital visits and improve certain patient outcomes related to diabetes, coronary artery disease, or heart failure. Patients who had nurse-led care were more satisfied and tended to receive more tests and medications. It is unclear whether specialized nurses improve quality of life or doctor workload. PMID:24194798

MR Imaging of the Penis and Scrotum.

PubMed

Parker, Rex A; Menias, Christine O; Quazi, Robin; Hara, Amy K; Verma, Sadhna; Shaaban, Akram; Siegel, Cary L; Radmanesh, Alireza; Sandrasegaran, Kumar

2015-01-01

Traditionally, due to its low cost, ready availability, and proved diagnostic accuracy, ultrasonography (US) has been the primary imaging modality for the evaluation of scrotal and, to a lesser extent, penile disease. However, US is limited by its relatively small useful field of view, operator dependence, and inability to provide much information on tissue characterization. Magnetic resonance (MR) imaging, with its excellent soft-tissue contrast and good spatial resolution, is increasingly being used as both a problem-solving tool in patients who have already undergone US and as a primary modality for the evaluation of suspected disease. Specifically, MR imaging can aid in differentiating between benign and malignant lesions seen at US, help define the extent of inflammatory processes or traumatic injuries, and play a vital role in locoregional staging of tumors. Consequently, it is becoming more important for radiologists to be familiar with the wide range of penile and scrotal disease entities and their MR imaging appearances. The authors review the basic anatomy of the penis and scrotum as seen at MR imaging and provide a basic protocol for penile and scrotal imaging, with emphasis on the advantages of MR imaging. Pathologic processes are organized into traumatic (including penile fracture and contusion), infectious or inflammatory (including Fournier gangrene and scrotal abscess), and neoplastic (including both benign and malignant scrotal and penile tumors) processes. ©RSNA, 2015.

RECODE: design and baseline results of a cluster randomized trial on cost-effectiveness of integrated COPD management in primary care.

PubMed

Kruis, Annemarije L; Boland, Melinde R S; Schoonvelde, Catharina H; Assendelft, Willem J J; Rutten-van Mölken, Maureen P M H; Gussekloo, Jacobijn; Tsiachristas, Apostolos; Chavannes, Niels H

2013-03-23

Favorable effects of formal pulmonary rehabilitation in selected moderate to severe COPD patients are well established. Few data are available on the effects and costs of integrated disease management (IDM) programs on quality of care and health status of COPD patients in primary care, representing a much larger group of COPD patients. Therefore, the RECODE trial assesses the long-term clinical and cost-effectiveness of IDM in primary care. RECODE is a cluster randomized trial with two years of follow-up, during which 40 clusters of primary care teams (including 1086 COPD patients) are randomized to IDM or usual care. The intervention started with a 2-day multidisciplinary course in which healthcare providers are trained as a team in essential components of effective COPD IDM in primary care. During the course, the team redesigns the care process and defines responsibilities of different caregivers. They are trained in how to use feedback on process and outcome data to guide implement guideline-driven integrated healthcare. Practice-tailored feedback reports are provided at baseline, and at 6 and 12 months. The team learns the details of an ICT program that supports recording of process and outcome measures. Afterwards, the team designs a time-contingent individual practice plan, agreeing on steps to be taken in order to integrate a COPD IDM program into daily practice. After 6 and 12 months, there is a refresher course for all teams simultaneously to enable them to learn from each other's experience. Health status of patients at 12 months is the primary outcome, measured by the Clinical COPD Questionnaire (CCQ). Secondary outcomes include effects on quality of care, disease-specific and generic health-related quality of life, COPD exacerbations, dyspnea, costs of healthcare utilization, and productivity loss. This article presents the protocol and baseline results of the RECODE trial. This study will allow to evaluate whether IDM implemented in primary care can positively influence quality of life and quality of care in mild to moderate COPD patients, thereby making the benefits of multidisciplinary rehabilitation applicable to a substantial part of the COPD population. Netherlands Trial Register (NTR): NTR2268.

A multifaceted strategy using mobile technology to assist rural primary healthcare doctors and frontline health workers in cardiovascular disease risk management: protocol for the SMARTHealth India cluster randomised controlled trial.

PubMed

Praveen, Devarsetty; Patel, Anushka; McMahon, Stephen; Prabhakaran, Dorairaj; Clifford, Gari D; Maulik, Pallab K; Joshi, Rohina; Jan, Stephen; Heritier, Stephane; Peiris, David

2013-11-25

Blood Pressure related disease affected 118 million people in India in the year 2000; this figure will double by 2025. Around one in four adults in rural India have hypertension, and of those, only a minority are accessing appropriate care. Health systems in India face substantial challenges to meet these gaps in care, and innovative solutions are needed. We hypothesise that a multifaceted intervention involving capacity strengthening of primary healthcare doctors and non-physician healthcare workers through use of a mobile device-based clinical decision support system will result in improved blood pressure control for individuals at high risk of a cardiovascular disease event when compared with usual healthcare. This intervention will be implemented as a stepped wedge, cluster randomised controlled trial in 18 primary health centres and 54 villages in rural Andhra Pradesh involving adults aged ≥40 years at high cardiovascular disease event risk (approximately 15,000 people). Cardiovascular disease event risk will be calculated based on World Health Organisation/International Society of Hypertension's region-specific risk charts. Cluster randomisation will occur at the level of the primary health centres. Outcome analyses will be conducted blinded to intervention allocation. The primary study outcome is the difference in the proportion of people meeting guideline-recommended blood pressure targets in the intervention period vs. the control period. Secondary outcomes include mean reduction in blood pressure levels; change in other cardiovascular disease risk factors, including body mass index, current smoking, reported healthy eating habits, and reported physical activity levels; self-reported use of blood pressure and other cardiovascular medicines; quality of life (using the EQ-5D); and cardiovascular disease events (using hospitalisation data). Trial outcomes will be accompanied by detailed process and economic evaluations. The findings are likely to inform policy on a scalable strategy to overcome entrenched inequities in access to effective healthcare for under-served populations in low and middle income country settings. Clinical Trial Registry India CTRI/2013/06/003753.

Integrated primary care in Germany: the road ahead.

PubMed

Schlette, Sophia; Lisac, Melanie; Blum, Kerstin

2009-04-20

Health care delivery in Germany is highly fragmented, resulting in poor vertical and horizontal integration and a system that is focused on curing acute illness or single diseases instead of managing patients with more complex or chronic conditions, or managing the health of determined populations. While it is now widely accepted that a strong primary care system can help improve coordination and responsiveness in health care, primary care has so far not played this role in the German system. Primary care physicians traditionally do not have a gatekeeper function; patients can freely choose and directly access both primary and secondary care providers, making coordination and cooperation within and across sectors difficult. Since 2000, driven by the political leadership and initiative of the Federal Ministry of Health, the German Bundestag has passed several laws enabling new forms of care aimed to improve care coordination and to strengthen primary care as a key function in the German health care system. These include on the contractual side integrated care contracts, and on the delivery side disease management programmes, medical care centres, gatekeeping and 'community medicine nurses'. Recent policy reforms improved framework conditions for new forms of care. There is a clear commitment by the government and the introduction of selective contracting and financial incentives for stronger cooperation constitute major drivers for change. First evaluations, especially of disease management programmes, indicate that the new forms of care improve coordination and outcomes. Yet the process of strengthening primary care as a lever for better care coordination has only just begun. Future reforms need to address other structural barriers for change such as fragmented funding streams, inadequate payment systems, the lack of standardized IT systems and trans-sectoral education and training of providers.

Integrated primary care in Germany: the road ahead

PubMed Central

Schlette, Sophia; Lisac, Melanie; Blum, Kerstin

2009-01-01

Problem statement Health care delivery in Germany is highly fragmented, resulting in poor vertical and horizontal integration and a system that is focused on curing acute illness or single diseases instead of managing patients with more complex or chronic conditions, or managing the health of determined populations. While it is now widely accepted that a strong primary care system can help improve coordination and responsiveness in health care, primary care has so far not played this role in the German system. Primary care physicians traditionally do not have a gatekeeper function; patients can freely choose and directly access both primary and secondary care providers, making coordination and cooperation within and across sectors difficult. Description of policy development Since 2000, driven by the political leadership and initiative of the Federal Ministry of Health, the German Bundestag has passed several laws enabling new forms of care aimed to improve care coordination and to strengthen primary care as a key function in the German health care system. These include on the contractual side integrated care contracts, and on the delivery side disease management programmes, medical care centres, gatekeeping and ‘community medicine nurses’. Conclusion and discussion Recent policy reforms improved framework conditions for new forms of care. There is a clear commitment by the government and the introduction of selective contracting and financial incentives for stronger cooperation constitute major drivers for change. First evaluations, especially of disease management programmes, indicate that the new forms of care improve coordination and outcomes. Yet the process of strengthening primary care as a lever for better care coordination has only just begun. Future reforms need to address other structural barriers for change such as fragmented funding streams, inadequate payment systems, the lack of standardized IT systems and trans-sectoral education and training of providers. PMID:19513180

GLIS1-3 transcription factors: critical roles in the regulation of multiple physiological processes and diseases.

PubMed

Jetten, Anton M

2018-05-19

Krüppel-like zinc finger proteins form one of the largest families of transcription factors. They function as key regulators of embryonic development and a wide range of other physiological processes, and are implicated in a variety of pathologies. GLI-similar 1-3 (GLIS1-3) constitute a subfamily of Krüppel-like zinc finger proteins that act either as activators or repressors of gene transcription. GLIS3 plays a critical role in the regulation of multiple biological processes and is a key regulator of pancreatic β cell generation and maturation, insulin gene expression, thyroid hormone biosynthesis, spermatogenesis, and the maintenance of normal kidney functions. Loss of GLIS3 function in humans and mice leads to the development of several pathologies, including neonatal diabetes and congenital hypothyroidism, polycystic kidney disease, and infertility. Single nucleotide polymorphisms in GLIS3 genes have been associated with increased risk of several diseases, including type 1 and type 2 diabetes, glaucoma, and neurological disorders. GLIS2 plays a critical role in the kidney and GLIS2 dysfunction leads to nephronophthisis, an end-stage, cystic renal disease. In addition, GLIS1-3 have regulatory functions in several stem/progenitor cell populations. GLIS1 and GLIS3 greatly enhance reprogramming efficiency of somatic cells into induced embryonic stem cells, while GLIS2 inhibits reprogramming. Recent studies have obtained substantial mechanistic insights into several physiological processes regulated by GLIS2 and GLIS3, while a little is still known about the physiological functions of GLIS1. The localization of some GLIS proteins to the primary cilium suggests that their activity may be regulated by a downstream primary cilium-associated signaling pathway. Insights into the upstream GLIS signaling pathway may provide opportunities for the development of new therapeutic strategies for diabetes, hypothyroidism, and other diseases.

Whole exome or genome sequencing: nurses need to prepare families for the possibilities.

PubMed

Prows, Cynthia A; Tran, Grace; Blosser, Beverly

2014-12-01

A discussion of whole exome sequencing and the type of possible results patients and families should be aware of before samples are obtained. To find the genetic cause of a rare disorder, whole exome sequencing analyses all known and suspected human genes from a single sample. Over 20,000 detected DNA variants in each individual exome must be considered as possibly causing disease or disregarded as not relevant to the person's disease. In the process, unexpected gene variants associated with known diseases unrelated to the primary purpose of the test may be incidentally discovered. Because family members' DNA samples are often needed, gene variants associated with known genetic diseases or predispositions for diseases can also be discovered in their samples. Discussion paper. PubMed 2009-2013, list of references in retrieved articles, Google Scholar. Nurses need a general understanding of the scope of potential genomic information that may be revealed with whole exome sequencing to provide support and guidance to individuals and families during their decision-making process, while waiting for results and after disclosure. Nurse scientists who want to use whole exome sequencing in their study design and methods must decide early in study development if they will return primary whole exome sequencing research results and if they will give research participants choices about learning incidental research results. It is critical that nurses translate their knowledge about whole exome sequencing into their patient education and patient advocacy roles and relevant programmes of research. © 2014 John Wiley & Sons Ltd.

Novel determinants of mammalian primary microRNA processing revealed by systematic evaluation of hairpin-containing transcripts and human genetic variation

PubMed Central

Roden, Christine; Gaillard, Jonathan; Kanoria, Shaveta; Rennie, William; Barish, Syndi; Cheng, Jijun; Pan, Wen; Liu, Jun; Cotsapas, Chris; Ding, Ye; Lu, Jun

2017-01-01

Mature microRNAs (miRNAs) are processed from hairpin-containing primary miRNAs (pri-miRNAs). However, rules that distinguish pri-miRNAs from other hairpin-containing transcripts in the genome are incompletely understood. By developing a computational pipeline to systematically evaluate 30 structural and sequence features of mammalian RNA hairpins, we report several new rules that are preferentially utilized in miRNA hairpins and govern efficient pri-miRNA processing. We propose that a hairpin stem length of 36 ± 3 nt is optimal for pri-miRNA processing. We identify two bulge-depleted regions on the miRNA stem, located ∼16–21 nt and ∼28–32 nt from the base of the stem, that are less tolerant of unpaired bases. We further show that the CNNC primary sequence motif selectively enhances the processing of optimal-length hairpins. We predict that a small but significant fraction of human single-nucleotide polymorphisms (SNPs) alter pri-miRNA processing, and confirm several predictions experimentally including a disease-causing mutation. Our study enhances the rules governing mammalian pri-miRNA processing and suggests a diverse impact of human genetic variation on miRNA biogenesis. PMID:28087842

Early Focal Segmental Glomerulosclerosis as a Cause of Renal Allograft Primary Nonfunction

PubMed Central

Griffin, Emma J.; Thomson, Peter C.; Kipgen, David; Clancy, Marc; Daly, Conal

2013-01-01

Background. Primary focal segmental glomerulosclerosis (FSGS) is one of the commonest causes of glomerular disease and if left untreated will often progress to established renal failure. In many cases the best treatment option is renal transplantation; however primary FSGS may rapidly recur in renal allografts and may contribute to delayed graft function. We present a case of primary nonfunction in a renal allograft due to biopsy-proven FSGS. Case Report. A 32-year-old man presented with serum albumin of 22 g/L, proteinuria quantified at 12 g/L, and marked peripheral oedema. Renal biopsy demonstrated tip-variant FSGS. Despite treatment, the patient developed progressive renal dysfunction and was commenced on haemodialysis. Cadaveric renal transplantation was undertaken; however this was complicated by primary nonfunction. Renal biopsies failed to demonstrate evidence of acute rejection but did demonstrate clear evidence of FSGS. The patient was treated to no avail. Discussion. Primary renal allograft nonfunction following transplantation is often due to acute kidney injury or acute rejection. Recurrent FSGS is recognised as a phenomenon that drives allograft dysfunction but is not traditionally associated with primary nonfunction. This case highlights FSGS as a potentially aggressive process that, once active in the allograft, may prove refractory to targeted treatment. Preemptive therapies in patients deemed to be at high risk of recurrent disease may be appropriate and should be considered. PMID:23781382

Inflammatory fatigue and sickness behaviour - lessons for the diagnosis and management of chronic fatigue syndrome.

PubMed

Arnett, S V; Clark, I A

2012-12-10

Persistent and severe fatigue is a common part of the presentation of a diverse range of disease processes. There is a growing body of evidence indicating a common inflammatory pathophysiology underlying many conditions where fatigue is a primary patient concern, including chronic fatigue syndrome. This review explores current models of how inflammatory mediators act on the central nervous system to produce fatigue and sickness behaviour, and the commonality of these processes in conditions as diverse as surgical trauma, infection, various cancers, inflammatory bowel disease, connective tissue diseases and autoimmune diseases. We also discuss evidence indicating chronic fatigue syndrome may have important pathophysiological similarities with cytokine mediated sickness behaviour, and what lessons can be applied from sickness behaviour to chronic fatigue syndrome with regards to the diagnosis and management. Copyright © 2012 Elsevier B.V. All rights reserved.

The activation pattern of macrophages in giant cell (temporal) arteritis and primary angiitis of the central nervous system.

PubMed

Mihm, Bernhard; Bergmann, Markus; Brück, Wolfgang; Probst-Cousin, Stefan

2014-06-01

To determine if the pattern of macrophage activation reflects differences in the pathogenesis and clinical presentation of giant cell arteritis and primary angiitis of the central nervous system, specimens of 10 patients with giant cell arteritis and five with primary angiitis of the central nervous system were immunohistochemically studied and the expression of the macrophage activation markers 27E10, MRP14, MRP8 and 25F9 was determined in the vasculitic infiltrates. Thus, a partly different expression pattern of macrophage activation markers in giant cell arteritis and primary angiitis of the central nervous system was observed. The group comparison revealed that giant cell arteritis cases had significantly higher numbers of acute activated MRP14-positive macrophages, whereas primary angiitis of the central nervous system is characterized by a tendency toward more MRP8-positive intermediate/late activated macrophages. Furthermore, in giant cell arteritis comparably fewer CD8-positive lymphocytes were observed. These observations suggest, that despite their histopathological similarities, giant cell arteritis and primary angiitis of the central nervous system appear to represent either distinct entities within the spectrum of granulomatous vasculitides or different stages of similar disease processes. Their discrete clinical presentation is reflected by different activation patterns of macrophages, which may characterize giant cell arteritis as a more acute process and primary angiitis of the central nervous system as a more advanced inflammatory process. © 2013 Japanese Society of Neuropathology.

The Evidential Basis of Decision Making in Plant Disease Management.

PubMed

Hughes, Gareth

2017-08-04

The evidential basis for disease management decision making is provided by data relating to risk factors. The decision process involves an assessment of the evidence leading to taking (or refraining from) action on the basis of a prediction. The primary objective of the decision process is to identify-at the time the decision is made-the control action that provides the best predicted end-of-season outcome, calculated in terms of revenue or another appropriate metric. Data relating to disease risk factors may take a variety of forms (e.g., continuous, discrete, categorical) on measurement scales in a variety of units. Log 10 -likelihood ratios provide a principled basis for the accumulation of evidence based on such data and allow predictions to be made via Bayesian updating of prior probabilities.

Medical care of type 2 diabetes in German disease management programmes: a population-based evaluation.

PubMed

Stark, Reneé G; Schunk, Michaela V; Meisinger, Christine; Rathmann, Wolfgang; Leidl, Reiner; Holle, Rolf

2011-05-01

Type 2 diabetes disease management programmes (DDMPs) are offered by German social health insurance to promote healthcare consistent with evidence-based medical guidelines. The aim of this study was to compare healthcare quality and medical endpoints between diabetes management programme participants and patients receiving usual care designated as controls. All patients with type 2 diabetes (age range: 36-81) in a cross-sectional survey of a cohort study, performed by the Cooperative Health Research in the Region of Augsburg, received a self-administered questionnaire regarding their diabetes care. Physical examination and laboratory tests were also performed. The analysis only included patients with social health insurance and whose participation status in a diabetes disease management program was validated by the primary physician (n = 166). Regression analyses, adjusting for age, sex, education, diabetes duration, baseline waist circumference and clustering regarding primary physician were conducted. Evaluation of healthcare processes showed that those in diabetes disease management programmes (n = 89) reported medical examination of eyes and feet and medical advice regarding diet [odds ratio (OR): 2.39] and physical activity (OR: 2.87) more frequently, received anti-diabetic medications (OR: 3.77) and diabetes education more often (OR: 2.66) than controls. Both groups had satisfactory HbA(1c) control but poor low-density lipoprotein cholesterol control. Blood pressure goals (<140/90 mmHg) were achieved more frequently by patients in diabetes disease management programmes (OR: 2.21). German diabetes disease management programmes are associated with improved healthcare processes and blood pressure control. Low-density lipoprotein cholesterol control must be improved for all patients with diabetes. Further research will be required to assess the long-term effects of this diabetes disease management programme. Copyright © 2011 John Wiley & Sons, Ltd.

Implementing change in primary care practices using electronic medical records: a conceptual framework.

PubMed

Nemeth, Lynne S; Feifer, Chris; Stuart, Gail W; Ornstein, Steven M

2008-01-16

Implementing change in primary care is difficult, and little practical guidance is available to assist small primary care practices. Methods to structure care and develop new roles are often needed to implement an evidence-based practice that improves care. This study explored the process of change used to implement clinical guidelines for primary and secondary prevention of cardiovascular disease in primary care practices that used a common electronic medical record (EMR). Multiple conceptual frameworks informed the design of this study designed to explain the complex phenomena of implementing change in primary care practice. Qualitative methods were used to examine the processes of change that practice members used to implement the guidelines. Purposive sampling in eight primary care practices within the Practice Partner Research Network-Translating Researching into Practice (PPRNet-TRIP II) clinical trial yielded 28 staff members and clinicians who were interviewed regarding how change in practice occurred while implementing clinical guidelines for primary and secondary prevention of cardiovascular disease and strokes. A conceptual framework for implementing clinical guidelines into primary care practice was developed through this research. Seven concepts and their relationships were modelled within this framework: leaders setting a vision with clear goals for staff to embrace; involving the team to enable the goals and vision for the practice to be achieved; enhancing communication systems to reinforce goals for patient care; developing the team to enable the staff to contribute toward practice improvement; taking small steps, encouraging practices' tests of small changes in practice; assimilating the electronic medical record to maximize clinical effectiveness, enhancing practices' use of the electronic tool they have invested in for patient care improvement; and providing feedback within a culture of improvement, leading to an iterative cycle of goal setting by leaders. This conceptual framework provides a mental model which can serve as a guide for practice leaders implementing clinical guidelines in primary care practice using electronic medical records. Using the concepts as implementation and evaluation criteria, program developers and teams can stimulate improvements in their practice settings. Investing in collaborative team development of clinicians and staff may enable the practice environment to be more adaptive to change and improvement.

Evaluation of a tailored implementation strategy to improve the management of patients with chronic obstructive pulmonary disease in primary care: a study protocol of a cluster randomized trial.

PubMed

Godycki-Cwirko, Maciek; Zakowska, Izabela; Kosiek, Katarzyna; Wensing, Michel; Krawczyk, Jaroslaw; Kowalczyk, Anna

2014-04-04

Chronic obstructive pulmonary disease (COPD) remains a major health problem, strongly related to smoking. Despite the publication of practice guidelines on prevention and treatment, not all patients with the disease receive the recommended healthcare, particularly with regard to smoking cessation advice where applicable. We have developed a tailored implementation strategy for enhancing general practitioners' adherence to the disease management guidelines. The primary aim of the study is to evaluate the effects of this tailored implementation intervention on general practitioners' adherence to guidelines. A pragmatic two-arm cluster randomized trial has been planned to compare care following the implementation of tailored interventions of four recommendations in COPD patients against usual care. The study will involve 18 general practices (9 in the intervention group and 9 in the control group) in Poland, each with at least 80 identified (at the baseline) patients with diagnosed COPD. The nine control practices will provide usual care without any interventions. Tailored interventions to implement four recommendations will be delivered in the remaining nine practices. At follow-up after nine months, data will be collected for all 18 general practices. The primary outcome measure is physicians' adherence to all four recommendations: brief anti-smoking advice, dyspnea assessment, care checklist utilization and demonstration to patients of correct inhaler use. This measurement will be based on data extracted from identified patients' records. Additionally, we will survey and interview patients with chronic obstructive pulmonary disease about the process of care. The results of this trial will be directly applicable to primary care in Poland and add to the growing body of evidence on interventions to improve chronic illness care. This trial has been registered with Clinical Trials Protocol Registration System. NCT01893476.

How predictive quantitative modelling of tissue organisation can inform liver disease pathogenesis.

PubMed

Drasdo, Dirk; Hoehme, Stefan; Hengstler, Jan G

2014-10-01

From the more than 100 liver diseases described, many of those with high incidence rates manifest themselves by histopathological changes, such as hepatitis, alcoholic liver disease, fatty liver disease, fibrosis, and, in its later stages, cirrhosis, hepatocellular carcinoma, primary biliary cirrhosis and other disorders. Studies of disease pathogeneses are largely based on integrating -omics data pooled from cells at different locations with spatial information from stained liver structures in animal models. Even though this has led to significant insights, the complexity of interactions as well as the involvement of processes at many different time and length scales constrains the possibility to condense disease processes in illustrations, schemes and tables. The combination of modern imaging modalities with image processing and analysis, and mathematical models opens up a promising new approach towards a quantitative understanding of pathologies and of disease processes. This strategy is discussed for two examples, ammonia metabolism after drug-induced acute liver damage, and the recovery of liver mass as well as architecture during the subsequent regeneration process. This interdisciplinary approach permits integration of biological mechanisms and models of processes contributing to disease progression at various scales into mathematical models. These can be used to perform in silico simulations to promote unravelling the relation between architecture and function as below illustrated for liver regeneration, and bridging from the in vitro situation and animal models to humans. In the near future novel mechanisms will usually not be directly elucidated by modelling. However, models will falsify hypotheses and guide towards the most informative experimental design. Copyright © 2014 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Physician perceptions of primary prevention: qualitative base for the conceptual shaping of a practice intervention tool

PubMed Central

Mirand, Amy L; Beehler, Gregory P; Kuo, Christina L; Mahoney, Martin C

2002-01-01

Background A practice intervention must have its basis in an understanding of the physician and practice to secure its benefit and relevancy. We used a formative process to characterize primary care physician attitudes, needs, and practice obstacles regarding primary prevention. The characterization will provide the conceptual framework for the development of a practice tool to facilitate routine delivery of primary preventive care. Methods A focus group of primary care physician Opinion Leaders was audio-taped, transcribed, and qualitatively analyzed to identify emergent themes that described physicians' perceptions of prevention in daily practice. Results The conceptual worth of primary prevention, including behavioral counseling, was high, but its practice was significantly countered by the predominant clinical emphasis on and rewards for secondary care. In addition, lack of health behavior training, perceived low self-efficacy, and patient resistance to change were key deterrents to primary prevention delivery. Also, the preventive focus in primary care is not on cancer, but on predominant chronic nonmalignant conditions. Conclusions The success of the future practice tool will be largely dependent on its ability to "fit" primary prevention into the clinical culture of diagnoses and treatment sustained by physicians, patients, and payers. The tool's message output must be formatted to facilitate physician delivery of patient-tailored behavioral counseling in an accurate, confident, and efficacious manner. Also, the tool's health behavior messages should be behavior-specific, not disease-specific, to draw on shared risk behaviors of numerous diseases and increase the likelihood of perceived salience and utility of the tool in primary care. PMID:12204096

Which interventions offer best value for money in primary prevention of cardiovascular disease?

PubMed

Cobiac, Linda J; Magnus, Anne; Lim, Stephen; Barendregt, Jan J; Carter, Rob; Vos, Theo

2012-01-01

Despite many decades of declining mortality rates in the Western world, cardiovascular disease remains the leading cause of death worldwide. In this research we evaluate the optimal mix of lifestyle, pharmaceutical and population-wide interventions for primary prevention of cardiovascular disease. In a discrete time Markov model we simulate the ischaemic heart disease and stroke outcomes and cost impacts of intervention over the lifetime of all Australian men and women, aged 35 to 84 years, who have never experienced a heart disease or stroke event. Best value for money is achieved by mandating moderate limits on salt in the manufacture of bread, margarine and cereal. A combination of diuretic, calcium channel blocker, ACE inhibitor and low-cost statin, for everyone with at least 5% five-year risk of cardiovascular disease, is also cost-effective, but lifestyle interventions aiming to change risky dietary and exercise behaviours are extremely poor value for money and have little population health benefit. There is huge potential for improving efficiency in cardiovascular disease prevention in Australia. A tougher approach from Government to mandating limits on salt in processed foods and reducing excessive statin prices, and a shift away from lifestyle counselling to more efficient absolute risk-based prescription of preventive drugs, could cut health care costs while improving population health.

Recent developments in the surgical management of perianal fistula for Crohn’s disease

PubMed Central

Geltzeiler, Cristina B.; Wieghard, Nicole; Tsikitis, Vassiliki L.

2014-01-01

Perianal manifestations of Crohn’s disease (CD) are common and, of them, fistulas are the most common. Perianal fistulas can be extremely debilitating for patients and are often very challenging for clinicians to treat. CD perianal fistulas usually require multidisciplinary and multimodality treatment, including both medical and surgical approaches. The majority of patients require multiple surgical interventions. CD patients with perianal fistulas have a high rate of primary non-healing, surgical morbidity, and high recurrence rates. This has led to constant efforts to improve surgical management of this disease process. PMID:25331917

Magnesium: Nutrition and Homoeostasis.

PubMed

Vormann, Jürgen

2016-01-01

The essential mineral magnesium is involved in numerous physiological processes. Recommended dietary intake is often not met and a low magnesium status increases the risk for various diseases. Magnesium status is regulated by several magnesium transport systems either in cellular or paracellular pathways. Numerous drugs either interfere with magnesium absorption in the intestines or the reabsorption from primary urine in the kidney. Low magnesium status has been identified as a significant risk factor for several diseases, including type-2 diabetes, cardiovascular diseases, arrhythmias, as well as general muscular and neurological problems. Therefore, an adequate magnesium supply would be of special benefit to our overall health.

A qualitative study of perceived needs and factors associated with the quality of care for common mental disorders in patients with chronic diseases: the perspective of primary care clinicians and patients.

PubMed

Roberge, Pasquale; Hudon, Catherine; Pavilanis, Alan; Beaulieu, Marie-Claude; Benoit, Annie; Brouillet, Hélène; Boulianne, Isabelle; De Pauw, Anna; Frigon, Serge; Gaboury, Isabelle; Gaudreault, Martine; Girard, Ariane; Giroux, Marie; Grégoire, Élyse; Langlois, Line; Lemieux, Martin; Loignon, Christine; Vanasse, Alain

2016-09-13

The prevalence of comorbid anxiety and depressive disorders is high among patients with chronic diseases in primary care, and is associated with increased morbidity and mortality rates. The detection and treatment of common mental disorders in patients with chronic diseases can be challenging in the primary care setting. This study aims to explore the perceived needs, barriers and facilitators for the delivery of mental health care for patients with coexisting common mental disorders and chronic diseases in primary care from the clinician and patient perspectives. In this qualitative descriptive study, we conducted semi-structured interviews with clinicians (family physician, nurse, psychologist, social worker; n = 18) and patients (n = 10) from three primary care clinics in Quebec, Canada. The themes explored included clinician factors (e.g., attitudes, perception of roles, collaboration, management of clinical priorities) and patient factors (e.g., needs, preferences, access to care, communication with health professionals) associated with the delivery of care. Qualitative data analysis was conducted based on an interactive cyclical process of data reduction, data display and conclusion drawing and verification. Clinician interviews highlighted a number of needs, barriers and enablers in the provision of patient services, which related to inter-professional collaboration, access to psychotherapy, polypharmacy as well as communication and coordination of services within the primary care clinic and the local network. Two specific facilitators associated with optimal mental health care were the broadening of nurses' functions in mental health care and the active integration of consulting psychiatrists. Patients corroborated the issues raised by the clinicians, particularly in the domains of whole-person care, service accessibility and care management. The results of this project will contribute to the development of quality improvement interventions to increase the uptake of organizational and clinical evidence-based practices for patients with chronic diseases and concurrent common mental disorders, in priority areas including collaborative care, access to psychotherapy and linkages with specialized mental health care.

Liquid nitrogen cryotherapy for surface eye disease (an AOS thesis).

PubMed

Fraunfelder, Frederick Web

2008-01-01

To evaluate the effects of new treatments with liquid nitrogen cryotherapy on some external eye conditions. In this retrospective case study, 6 separate series from a single tertiary care referral center practice are described. Liquid nitrogen cryotherapy was used to treat conjunctival amyloidosis, primary pterygia, recurrent pterygia, advancing wavelike epitheliopathy (AWLE), superior limbic keratoconjunctivitis (SLK), and palpebral vernal keratoconjunctivitis (VKC). The main outcome measure was the resolution of the disease process after treatment. Four patients with primary localized conjunctival amyloidosis were treated with liquid nitrogen cryotherapy. Two of them had recurrence of the amyloidosis, which cleared with subsequent treatment. Eighteen patients with primary pterygia had excision and cryotherapy with 1 recurrence. Of 6 subjects who presented with recurrent pterygia, 4 had a second recurrence after excision and cryotherapy. In 5 patients with AWLE, the condition resolved within 2 weeks without recurrence or the need for subsequent cryotherapy. Four patients with SLK were treated with liquid nitrogen cryotherapy. Disease recurred in 2 patients and 3 of 7 eyes, although subsequent cryotherapy eradicated SLK in all cases. Two patients and 3 eyelids with palpebral VKC were treated with liquid nitrogen cryotherapy. VKC recurred in all cases. Liquid nitrogen cryotherapy to the surface of the eye is effective in treating AWLE, and SLK. Excision followed by cryotherapy is successful in treating conjunctival amyloidosis and primary pterygia Liquid nitrogen cryotherapy is unsuccessful in the treatment of recurrent pterygia and VKC.

[Multimorbidity and primary care: Emergence of new forms of network organization].

PubMed

Lamothe, Lise; Sylvain, Chantal; Sit, Vanessa

2015-01-01

This study was designed to analyse the adaptive strategies used by primary care professionals to provide more adapted and continuous services to patients with more than one chronic disease. A qualitative case study was conducted in a primary care structure (GMF in Québec). Data were derived from two sources: semi-structured interviews and documents. Based on our thematic analysis of data, we illustrate the adaptive processes at play. Our analysis identified the challenges raised by the increased prevalence of patients with more than one chronic disease and how they influence adaptive strategic initiatives from professionals at the following levels: (1) the patients themselves, (2) the professional-patient relationship, (3) the relationships between professionals of the GMF (4) the relationships between the GMF and other healthcare organizations. The description of these phenomena illustrates the dynamic emergence ofa network form of organization. This phenomenon leads to transformation of the core of the healthcare production system. A deeper understanding of its emergence, impacts and management is necessary.

Do Independent Sector Treatment Centres (ISTC) impact on specialist registrar training in primary hip and knee arthroplasty?

PubMed

Clamp, Jonathan A; Baiju, Dean; Copas, David P; Hutchinson, James W; Rowles, John M

2008-09-01

The introduction of Modernising Medical Careers (MMC) is likely to reduce specialist registrar (SpR) operative experience during higher surgical training (HST). A further negative impact on training by local Independent Sector Treatment Centres (ISTCs) could reduce experience, and thus competence, in primary joint arthroplasty at completion of higher surgical training. Retrospective case note and radiograph analysis of patients receiving primary hip and knee arthroplasty in a teaching hospital, before and after the establishment of a local ISTC. Patients and operative details were recorded from the selected case notes. Corresponding radiographs were assessed and the severity of the disease process assessed. Fewer primary hip and knee replacements were performed by SpRs in the time period after the establishment of an ISTC. ISTCs may adversely affect SpR training in primary joint arthroplasty.

Value of primordial and primary prevention for cardiovascular disease: a policy statement from the American Heart Association.

PubMed

Weintraub, William S; Daniels, Stephen R; Burke, Lora E; Franklin, Barry A; Goff, David C; Hayman, Laura L; Lloyd-Jones, Donald; Pandey, Dilip K; Sanchez, Eduardo J; Schram, Andrea Parsons; Whitsel, Laurie P

2011-08-23

The process of atherosclerosis may begin in youth and continue for decades, leading to both nonfatal and fatal cardiovascular events, including myocardial infarction, stroke, and sudden death. With primordial and primary prevention, cardiovascular disease is largely preventable. Clinical trial evidence has shown convincingly that pharmacological treatment of risk factors can prevent events. The data are less definitive but also highly suggestive that appropriate public policy and lifestyle interventions aimed at eliminating tobacco use, limiting salt consumption, encouraging physical exercise, and improving diet can prevent events. There has been concern about whether efforts aimed at primordial and primary prevention provide value (ie, whether such interventions are worth what we pay for them). Although questions about the value of therapeutics for acute disease may be addressed by cost-effectiveness analysis, the long time frames involved in evaluating preventive interventions make cost-effectiveness analysis difficult and necessarily flawed. Nonetheless, cost-effectiveness analyses reviewed in this policy statement largely suggest that public policy, community efforts, and pharmacological intervention are all likely to be cost-effective and often cost saving compared with common benchmarks. The high direct medical care and indirect costs of cardiovascular disease-approaching $450 billion a year in 2010 and projected to rise to over $1 trillion a year by 2030-make this a critical medical and societal issue. Prevention of cardiovascular disease will also provide great value in developing a healthier, more productive society.

Can Tissue Cilia Lengths and Urine Cilia Proteins Be Markers of Kidney Diseases?

PubMed

Park, Kwon Moo

2018-05-01

The primary cilium is an organelle which consists of a microtubule in the core and a surrounding cilia membrane, and has long been recognized as a "vestigial organelle". However, new evidence demonstrates that the primary cilium has a notable effect on signal transduction in the cell and is associated with some genetic and non-genetic diseases. In the kidney, the primary cilium protrudes into the Bowman's space and the tubular lumen from the apical side of epithelial cells. The length of primary cilia is dynamically altered during the normal cell cycle, being shortened by retraction into the cell body at the entry of cell division and elongated at differentiation. Furthermore, the length of primary cilia is also dynamically changed in the cells, as a result and/or cause, during the progression of various kidney diseases including acute kidney injury and chronic kidney disease. Notably, recent data has demonstrated that the shortening of the primary cilium in the cell is associated with fragmentation, apart from retraction into the cell body, in the progression of diseases and that the fragmented primary cilia are released into the urine. This data reveals that the alteration of primary cilia length could be related to the progression of diseases. This review will consider if primary cilia length alteration is associated with the progression of kidney diseases and if the length of tissue primary cilia and the presence or increase of cilia proteins in the urine is indicative of kidney diseases.

Intestinal microbiota in primary sclerosing cholangitis.

PubMed

Hov, Johannes R; Kummen, Martin

2017-03-01

Alterations of the gut-liver axis have been linked to the pathogenesis of primary sclerosing cholangitis (PSC) since the disease was first described. The purpose of this review is to discuss multiple recent studies on the intestinal microbiota in human PSC and experimental models of this disease. Data are available from eight cross-sectional studies of human PSC, which include a variable number of patients (n = 11-85), material (mucosal or fecal), and microbiota profiling methodology. Despite the heterogeneity of the studies, a pattern of differences is observed that could represent a theme or signature of the PSC gut microbiota, characterized by low diversity and with alterations in multiple bacterial taxa. In experimental models of PSC, re-derivation of animals into germ-free facilities may either aggravate or attenuate the disease, depending on host genetics and putative disease mechanisms (e.g., fibrotic or immune-driven processes, respectively). The present data provide a strong rationale to explore the functional consequences of the observed gut microbial alterations and their influence on the pathogenesis in PSC. Studies of gut microbiota as biomarker and treatment target may potentially also lead to early translation into clinical practice.

A common presentation to an uncommon disease. Penile Mondor's disease: a case report and literature review.

PubMed

Walsh, John C; Poimboeuf, Sabré; Garvin, Daniel S

2014-01-01

Penile Mondor's disease, or superficial thrombophlebitis of the dorsal vein of the penis, is a relatively uncommon but potentially anxiety-inducing self-limiting condition that should be easily recognizable by any primary care practitioner. It typically presents with a cord-like mass and pain to the dorsal penis and has a myriad of causes, including trauma, excessive sexual activity, excessive exercise, or malignancy. Although Penile Mondor's disease is typically a clinical diagnosis, Doppler ultrasound is the initial imaging modality of choice if there is question or doubt about the diagnosis. Accurate diagnosis and reassurance about the condition's benign and self-limiting nature assuages most patients' fears. Treatment is primarily symptomatic but may vary depending on possible underlying disease processes.

The road to JCAHO disease-specific care certification: a step-by-step process log.

PubMed

Morrison, Kathy

2005-01-01

In 2002, the Joint Commission on Accreditation of Healthcare Organizations (JCAHO) implemented Disease-Specific Care (DSC) certification. This is a voluntary program in which organizations have their disease management program evaluated by this regulatory agency. Some of the DSC categories are stroke, heart failure, acute MI, diabetes, and pneumonia. The criteria for any disease management program certification are: compliance with consensus-based national standards, effective use of established clinical practice guidelines to manage and optimize care, and an organized approach to performance measurement and improvement activities. Successful accomplishment of DSC certification defines organizations as Centers of Excellence in management of that particular disease. This article will review general guidelines for DSC certification with an emphasis on Primary Stroke Center certification.

SMN control of RNP assembly: from post-transcriptional gene regulation to motor neuron disease

PubMed Central

Li, Darrick K.; Tisdale, Sarah; Lotti, Francesco; Pellizzoni, Livio

2014-01-01

At the post-transcriptional level, expression of protein-coding genes is controlled by a series of RNA regulatory events including nuclear processing of primary transcripts, transport of mature mRNAs to specific cellular compartments, translation and ultimately, turnover. These processes are orchestrated through the dynamic association of mRNAs with RNA binding proteins and ribonucleoprotein (RNP) complexes. Accurate formation of RNPs in vivo is fundamentally important to cellular development and function, and its impairment often leads to human disease. The survival motor neuron (SMN) protein is key to this biological paradigm: SMN is essential for the biogenesis of various RNPs that function in mRNA processing, and genetic mutations leading to SMN deficiency cause the neurodegenerative disease spinal muscular atrophy. Here we review the expanding role of SMN in the regulation of gene expression through its multiple functions in RNP assembly. We discuss advances in our understanding of SMN activity as a chaperone of RNPs and how disruption of SMN-dependent RNA pathways can cause motor neuron disease. PMID:24769255

Improving cardiovascular outcomes among Aboriginal Australians: Lessons from research for primary care.

PubMed

Thompson, Sandra C; Haynes, Emma; Woods, John A; Bessarab, Dawn C; Dimer, Lynette A; Wood, Marianne M; Sanfilippo, Frank M; Hamilton, Sandra J; Katzenellenbogen, Judith M

2016-01-01

The Aboriginal people of Australia have much poorer health and social indicators and a substantial life expectancy gap compared to other Australians, with premature cardiovascular disease a major contributor to poorer health. This article draws on research undertaken to examine cardiovascular disparities and focuses on ways in which primary care practitioners can contribute to reducing cardiovascular disparities and improving Aboriginal health. The overall research utilised mixed methods and included data analysis, interviews and group processes which included Aboriginal people, service providers and policymakers. Workshop discussions to identify barriers and what works were recorded by notes and on whiteboards, then distilled and circulated to participants and other stakeholders to refine and validate information. Additional engagement occurred through circulation of draft material and further discussions. This report distils the lessons for primary care practitioners to improve outcomes through management that is attentive to the needs of Aboriginal people. Aspects of primordial, primary and secondary prevention are identified, with practical strategies for intervention summarised. The premature onset and high incidence of Aboriginal cardiovascular disease make prevention imperative and require that primary care practitioners understand and work to address the social underpinnings of poor health. Doctors are well placed to reinforce the importance of healthy lifestyle at all visits to involve the family and to reduce barriers which impede early care seeking. Ensuring better information for Aboriginal patients and better integrated care for patients who frequently have complex needs and multi-morbidities will also improve care outcomes. Primary care practitioners have an important role in improving Aboriginal cardiovascular care outcomes. It is essential that they recognise the special needs of their Aboriginal patients and work at multiple levels both outside and inside the clinic for prevention and management of disease. A toolkit of proactive and holistic opportunities for interventions is proposed.

The Cardiovascular Health in Ambulatory Care Research Team performance indicators for the primary prevention of cardiovascular disease: a modified Delphi panel study.

PubMed

Tu, Jack V; Maclagan, Laura C; Ko, Dennis T; Atzema, Clare L; Booth, Gillian L; Johnston, Sharon; Tu, Karen; Lee, Douglas S; Bierman, Arlene; Hall, Ruth; Bhatia, R Sacha; Gershon, Andrea S; Tobe, Sheldon W; Sanmartin, Claudia; Liu, Peter; Chu, Anna

2017-04-25

High-quality ambulatory care can reduce cardiovascular disease risk, but important gaps exist in the provision of cardiovascular preventive care. We sought to develop a set of key performance indicators that can be used to measure and improve cardiovascular care in the primary care setting. As part of the Cardiovascular Health in Ambulatory Care Research Team initiative, we established a 14-member multidisciplinary expert panel to develop a set of indicators for measuring primary prevention performance in ambulatory cardiovascular care. We used a 2-stage modified Delphi panel process to rate potential indicators, which were identified from the literature and national cardiovascular organizations. The top-rated indicators were pilot tested to determine their measurement feasibility with the use of data routinely collected in the Canadian health care system. A set of 28 indicators of primary prevention performance were identified, which were grouped into 5 domains: risk factor prevalence, screening, management, intermediate outcomes and long-term outcomes. The indicators reflect the major cardiovascular risk factors including smoking, obesity, hypertension, diabetes, dyslipidemia and atrial fibrillation. All indicators were determined to be amenable to measurement with the use of population-based administrative (physician claims, hospital admission, laboratory, medication), survey or electronic medical record databases. The Cardiovascular Health in Ambulatory Care Research Team indicators of primary prevention performance provide a framework for the measurement of cardiovascular primary prevention efforts in Canada. The indicators may be used by clinicians, researchers and policy-makers interested in measuring and improving the prevention of cardiovascular disease in ambulatory care settings. Copyright 2017, Joule Inc. or its licensors.

Primary immunodeficiency disease: a model for case management of chronic diseases.

PubMed

Burton, Janet; Murphy, Elyse; Riley, Patty

2010-01-01

Patient-centered chronic care management is a new model for the management of rare chronic diseases such as primary immunodeficiency disease (PIDD). This approach emphasizes helping patients become experts on the management of their disease as informed, involved, and interactive partners in healthcare decisions with providers. Because only a few patients are affected by rare illnesses, these patients are forced to become knowledgeable about their disease and therapies and to seek treatment from a healthcare team, which includes physicians and nurse specialists who are equipped to manage the complexity of the disease and its comorbidities. Importantly, therapy for PIDD can be self-administered at home, which has encouraged the transition toward a proactive stance that is at the heart of patient-centered chronic care management. We discuss the evolution of therapy, the issues with the disease, and challenges with its management within the framework of other chronic disease management programs. Suggestions and rationale to move case management of PIDD forward are presented with the intent that sharing our experiences will improve process and better manage outcomes in this patient population. The patient-centered model for the management of PIDD is applicable to the primary care settings, where nurse case managers assist patients through education, support them and their families, and facilitate access to community resources in an approach, which has been described as "guided care." The model also applies specifically to immunology centers where patients receive treatment or instruction on its self-administration at home. Patient-centered management of PIDD, with its emphasis on full involvement of patients in their treatment, has the potential to improve compliance with treatment, and thus patient outcomes, as well as patients' quality of life. The patient-centered model expands the traditional model of chronic disease management, which relies on evidence-based medicine, provider expertise, clinical information systems, and patient education. This approach supports patient self-management with strategies that empower and prepare them for their role as expert patients.

Modeling congenital disease and inborn errors of development in Drosophila melanogaster

PubMed Central

Moulton, Matthew J.; Letsou, Anthea

2016-01-01

ABSTRACT Fly models that faithfully recapitulate various aspects of human disease and human health-related biology are being used for research into disease diagnosis and prevention. Established and new genetic strategies in Drosophila have yielded numerous substantial successes in modeling congenital disorders or inborn errors of human development, as well as neurodegenerative disease and cancer. Moreover, although our ability to generate sequence datasets continues to outpace our ability to analyze these datasets, the development of high-throughput analysis platforms in Drosophila has provided access through the bottleneck in the identification of disease gene candidates. In this Review, we describe both the traditional and newer methods that are facilitating the incorporation of Drosophila into the human disease discovery process, with a focus on the models that have enhanced our understanding of human developmental disorders and congenital disease. Enviable features of the Drosophila experimental system, which make it particularly useful in facilitating the much anticipated move from genotype to phenotype (understanding and predicting phenotypes directly from the primary DNA sequence), include its genetic tractability, the low cost for high-throughput discovery, and a genome and underlying biology that are highly evolutionarily conserved. In embracing the fly in the human disease-gene discovery process, we can expect to speed up and reduce the cost of this process, allowing experimental scales that are not feasible and/or would be too costly in higher eukaryotes. PMID:26935104

Feedback GAP: study protocol for a cluster-randomized trial of goal setting and action plans to increase the effectiveness of audit and feedback interventions in primary care

PubMed Central

2010-01-01

Background Audit and feedback to physicians is commonly used alone or as part of multifaceted interventions. While it can play an important role in quality improvement, the optimal design of audit and feedback is unknown. This study explores how feedback can be improved to increase acceptability and usability in primary care. The trial seeks to determine whether a theory-informed worksheet appended to feedback reports can help family physicians improve quality of care for their patients with diabetes and/or ischemic heart disease. Methods Two-arm cluster trial was conducted with participating primary care practices allocated using minimization to simple feedback or enhanced feedback group. The simple feedback group receives performance feedback reports every six months for two years regarding the proportion of their patients with diabetes and/or ischemic heart disease who are meeting quality targets. The enhanced feedback group receives these same reports as well as a theory-informed worksheet designed to facilitate goal setting and action plan development in response to the feedback reports. Participants are family physicians from across Ontario who use electronic medical records; data for rostered patients are used to produce the feedback reports and for analysis. Outcomes The primary disease outcomes are the blood pressure (BP), and low-density lipoprotein cholesterol (LDL) levels. The primary process measure is a composite score indicating the number of recommended activities (e.g., tests and prescriptions) conducted by the family physicians for their patients with diabetes and/or ischemic heart disease within the appropriate timeframe. Secondary outcomes are the proportion of patients whose results meet targets for glucose, LDL, and BP as well as the percent of patients receiving relevant prescriptions. A qualitative process evaluation using semi-structured interviews will explore perceived barriers to behaviour change in response to feedback reports and preferences with regard to feedback design. Analysis Intention-to-treat approach will be used to analyze the trial. Analysis will be performed on patient-level variables using generalized estimating equation models to adjust for covariates and account for the clustered nature of the data. The trial is powered to show small, but clinically important differences of 7 mmHG in systolic BP and 0.32 mmol/L in LDL. Trial Registration ClinicalTrials.gov NCT00996645 PMID:21167034

Feedback GAP: study protocol for a cluster-randomized trial of goal setting and action plans to increase the effectiveness of audit and feedback interventions in primary care.

PubMed

Ivers, Noah M; Tu, Karen; Francis, Jill; Barnsley, Jan; Shah, Baiju; Upshur, Ross; Kiss, Alex; Grimshaw, Jeremy M; Zwarenstein, Merrick

2010-12-17

Audit and feedback to physicians is commonly used alone or as part of multifaceted interventions. While it can play an important role in quality improvement, the optimal design of audit and feedback is unknown. This study explores how feedback can be improved to increase acceptability and usability in primary care. The trial seeks to determine whether a theory-informed worksheet appended to feedback reports can help family physicians improve quality of care for their patients with diabetes and/or ischemic heart disease. Two-arm cluster trial was conducted with participating primary care practices allocated using minimization to simple feedback or enhanced feedback group. The simple feedback group receives performance feedback reports every six months for two years regarding the proportion of their patients with diabetes and/or ischemic heart disease who are meeting quality targets. The enhanced feedback group receives these same reports as well as a theory-informed worksheet designed to facilitate goal setting and action plan development in response to the feedback reports. Participants are family physicians from across Ontario who use electronic medical records; data for rostered patients are used to produce the feedback reports and for analysis. The primary disease outcomes are the blood pressure (BP), and low-density lipoprotein cholesterol (LDL) levels. The primary process measure is a composite score indicating the number of recommended activities (e.g., tests and prescriptions) conducted by the family physicians for their patients with diabetes and/or ischemic heart disease within the appropriate timeframe. Secondary outcomes are the proportion of patients whose results meet targets for glucose, LDL, and BP as well as the percent of patients receiving relevant prescriptions. A qualitative process evaluation using semi-structured interviews will explore perceived barriers to behaviour change in response to feedback reports and preferences with regard to feedback design. Intention-to-treat approach will be used to analyze the trial. Analysis will be performed on patient-level variables using generalized estimating equation models to adjust for covariates and account for the clustered nature of the data. The trial is powered to show small, but clinically important differences of 7 mmHG in systolic BP and 0.32 mmol/L in LDL. ClinicalTrials.gov NCT00996645.

The Protective Effect of Lipoic Acid on Selected Cardiovascular Diseases Caused by Age-Related Oxidative Stress

PubMed Central

Goraca, Anna

2015-01-01

Oxidative stress is considered to be the primary cause of many cardiovascular diseases, including endothelial dysfunction in atherosclerosis and ischemic heart disease, hypertension, and heart failure. Oxidative stress increases during the aging process, resulting in either increased reactive oxygen species (ROS) production or decreased antioxidant defense. The increase in the incidence of cardiovascular disease is directly related to age. Aging is also associated with oxidative stress, which in turn leads to accelerated cellular senescence and organ dysfunction. Antioxidants may help lower the incidence of some pathologies of cardiovascular diseases and have antiaging properties. Lipoic acid (LA) is a natural antioxidant which is believed to have a beneficial effect on oxidative stress parameters in relation to diseases of the cardiovascular system. PMID:25949771

Salivary dysfunction associated with systemic diseases: systematic review and clinical management recommendations.

PubMed

von Bültzingslöwen, Inger; Sollecito, Thomas P; Fox, Philip C; Daniels, Troy; Jonsson, Roland; Lockhart, Peter B; Wray, David; Brennan, Michael T; Carrozzo, Marco; Gandera, Beatrice; Fujibayashi, Takashi; Navazesh, Mahvash; Rhodus, Nelson L; Schiødt, Morten

2007-03-01

The objective of this study was to identify systemic diseases associated with hyposalivation and xerostomia and develop evidence-based management recommendations for hyposalivation/xerostomia. Literature searches covered the English language medical literature from 1966 to 2005. An evidence-based review process was applied to management studies published from 2002 to 2005. Several systemic diseases were identified. From studies published 2002 to 2005, 15 were identified as high-quality studies and were used to support management recommendations: pilocarpine and cevimeline are recommended for treating hyposalivation and xerostomia in primary and secondary Sjögren's syndrome (SS). IFN-alpha lozenges may enhance saliva flow in primary SS patients. Anti-TNF-alpha agents, such as infliximab or etanercept, are not recommended to treat hyposalivation in SS. Dehydroepiandrosterone is not recommended to relieve hyposalivation or xerostomia in primary SS. There was not enough evidence to support any recommendations for the use of local stimulants, lubricants, and protectants for hyposalivation/xerostomia. However, professional judgment and patient preferences may support the use of a specific product for an individual patient. These evidence-based management recommendations should guide the clinician's management decisions for patients with salivary dysfunction related to systemic disease. Future treatment strategies may include new formulations of existing drugs, e.g., local application of pilocarpine. Recent discoveries on gene expression and a better understanding of the etiopathogenesis of SS may open new treatment options in the future.

European Consensus on Primary Prevention of Coronary Heart Disease.

PubMed

Assmann, G

1988-07-01

The European Consensus on Primary Prevention of Coronary Heart Disease has recommended that providing care for individuals at particular risk for coronary artery disease (CAD) requires case finding through medical examinations in primary care, hospital and employment health examination settings. Decisions concerning management of elevated lipid levels should be based on overall cardiovascular risk. The goal of reducing cholesterol levels through risk reduction can ultimately be accomplished only with the implementation of health education efforts directed toward all age groups and actions by government and supranational agencies, including adequate food labelling to identify fat content, selective taxation to encourage healthful habits and wider availability of exercise facilities. Only measures directed at the overall population can eventually reach the large proportion of individuals at mildly to moderately increased risk for CAD. The European Policy Statement on the Prevention of Coronary Heart Disease recognizes that the question of lipid elevation as a risk factor for CAD involves assessment, not only of cholesterol level alone, but also of triglycerides and the HDL cholesterol lipid fraction. Five specific categories of dyslipidemia have been identified, with individualized screening and treatment strategies advised for each. It is the consensus of the study group panel members that these procedures are both practical and feasible. They begin the necessary long term process to reduce the unacceptably high levels of morbidity and mortality due to CAD throughout the European community.

Pathology of Podocytopathies Causing Nephrotic Syndrome in Children.

PubMed

Ranganathan, Sarangarajan

2016-01-01

Nephrotic syndrome (NS) in children includes a diverse group of diseases that range from genetic diseases without any immunological defects to causes that are primarily due to immunological effects. Recent advances in molecular and genomic studies have resulted in a plethora of genetic defects that have been localized to the podocyte, the basic structure that is instrumental in normal filtration process. Although the disease can manifest from birth and into adulthood, the primary focus of this review would be to describe the novel genes and pathology of primary podocyte defects that cause NS in children. This review will restrict itself to the pathology of congenital NS, minimal change disease (MCD), and its variants and focal segmental glomerulosclerosis (FSGS). The two major types of congenital NS are Finnish type characterized by dilated sausage shaped tubules morphologically and diffuse mesangial sclerosis characterized by glomerulosclerosis. MCD has usually normal appearing biopsy features on light microscopy and needs electron microscopy for diagnosis, whereas FSGS in contrast has classic segmental sclerosing lesions identified in different portions of the glomeruli and tubular atrophy. This review summarizes the pathological characteristics of these conditions and also delves into the various genetic defects that have been described as the cause of these primary podocytopathies. Other secondary causes of NS in children, such as membranoproliferative and membranous glomerulonephritis, will not be covered in this review.

Systems-level mechanisms of action of Panax ginseng: a network pharmacological approach.

PubMed

Park, Sa-Yoon; Park, Ji-Hun; Kim, Hyo-Su; Lee, Choong-Yeol; Lee, Hae-Jeung; Kang, Ki Sung; Kim, Chang-Eop

2018-01-01

Panax ginseng has been used since ancient times based on the traditional Asian medicine theory and clinical experiences, and currently, is one of the most popular herbs in the world. To date, most of the studies concerning P. ginseng have focused on specific mechanisms of action of individual constituents. However, in spite of many studies on the molecular mechanisms of P. ginseng , it still remains unclear how multiple active ingredients of P. ginseng interact with multiple targets simultaneously, giving the multidimensional effects on various conditions and diseases. In order to decipher the systems-level mechanism of multiple ingredients of P. ginseng , a novel approach is needed beyond conventional reductive analysis. We aim to review the systems-level mechanism of P. ginseng by adopting novel analytical framework-network pharmacology. Here, we constructed a compound-target network of P. ginseng using experimentally validated and machine learning-based prediction results. The targets of the network were analyzed in terms of related biological process, pathways, and diseases. The majority of targets were found to be related with primary metabolic process, signal transduction, nitrogen compound metabolic process, blood circulation, immune system process, cell-cell signaling, biosynthetic process, and neurological system process. In pathway enrichment analysis of targets, mainly the terms related with neural activity showed significant enrichment and formed a cluster. Finally, relative degrees analysis for the target-disease association of P. ginseng revealed several categories of related diseases, including respiratory, psychiatric, and cardiovascular diseases.

GSTM1 null polymorphism at the glutathione S-transferase M1 locus: phenotype and genotype studies in patients with primary biliary cirrhosis.

PubMed Central

Davies, M H; Elias, E; Acharya, S; Cotton, W; Faulder, G C; Fryer, A A; Strange, R C

1993-01-01

Studies were carried out to test the hypothesis that the GSTM1 null phenotype at the mu (mu) class glutathione S-transferase 1 locus is associated with an increased predisposition to primary biliary cirrhosis. Starch gel electrophoresis was used to compare the prevalence of GSTM1 null phenotype 0 in patients with end stage primary biliary cirrhosis and a group of controls without evidence of liver disease. The prevalence of GSTM1 null phenotype in the primary biliary cirrhosis and control groups was similar; 39% and 45% respectively. In the primary biliary cirrhosis group all subjects were of the common GSTM1 0, GSTM1 A, GSTM1 B or GSTM1 A, B phenotypes while in the controls, one subject showed an isoform with an anodal mobility compatible with it being a product of the putative GSTM1*3 allele. As the GSTM1 phenotype might be changed by the disease process, the polymerase chain reaction was used to amplify the exon 4-exon 5 region of GSTM1 and show that in 13 control subjects and 11 patients with primary biliary cirrhosis, GSTM1 positive and negative genotypes were associated with corresponding GSTM1 expressing and non-expressing phenotypes respectively. The control subject with GSTM1 3 phenotype showed a positive genotype. Images Figure 1 Figure 2 PMID:8491405

Spreaders and Sponges define metastasis in lung cancer: A Markov chain Monte Carlo Mathematical Model

PubMed Central

Newton, Paul K.; Mason, Jeremy; Bethel, Kelly; Bazhenova, Lyudmila; Nieva, Jorge; Norton, Larry; Kuhn, Peter

2013-01-01

The classic view of metastatic cancer progression is that it is a unidirectional process initiated at the primary tumor site, progressing to variably distant metastatic sites in a fairly predictable, though not perfectly understood, fashion. A Markov chain Monte Carlo mathematical approach can determine a pathway diagram that classifies metastatic tumors as ‘spreaders’ or ‘sponges’ and orders the timescales of progression from site to site. In light of recent experimental evidence highlighting the potential significance of self-seeding of primary tumors, we use a Markov chain Monte Carlo (MCMC) approach, based on large autopsy data sets, to quantify the stochastic, systemic, and often multi-directional aspects of cancer progression. We quantify three types of multi-directional mechanisms of progression: (i) self-seeding of the primary tumor; (ii) re-seeding of the primary tumor from a metastatic site (primary re-seeding); and (iii) re-seeding of metastatic tumors (metastasis re-seeding). The model shows that the combined characteristics of the primary and the first metastatic site to which it spreads largely determine the future pathways and timescales of systemic disease. For lung cancer, the main ‘spreaders’ of systemic disease are the adrenal gland and kidney, whereas the main ‘sponges’ are regional lymph nodes, liver, and bone. Lung is a significant self-seeder, although it is a ‘sponge’ site with respect to progression characteristics. PMID:23447576

Alkaline Phosphatases in the Complex Chronic Kidney Disease-Mineral and Bone Disorders.

PubMed

Bover, Jordi; Ureña, Pablo; Aguilar, Armando; Mazzaferro, Sandro; Benito, Silvia; López-Báez, Víctor; Ramos, Alejandra; daSilva, Iara; Cozzolino, Mario

2018-02-14

Alkaline phosphatases (APs) remove the phosphate (dephosphorylation) needed in multiple metabolic processes (from many molecules such as proteins, nucleotides, or pyrophosphate). Therefore, APs are important for bone mineralization but paradoxically they can also be deleterious for other processes, such as vascular calcification and the increasingly known cross-talk between bone and vessels. A proper balance between beneficial and harmful activities is further complicated in the context of chronic kidney disease (CKD). In this narrative review, we will briefly update the complexity of the enzyme, including its different isoforms such as the bone-specific alkaline phosphatase or the most recently discovered B1x. We will also analyze the correlations and potential discrepancies with parathyroid hormone and bone turnover and, most importantly, the valuable recent associations of AP's with cardiovascular disease and/or vascular calcification, and survival. Finally, a basic knowledge of the synthetic and degradation pathways of APs promises to open new therapeutic strategies for the treatment of the CKD-Mineral and Bone Disorder (CKD-MBD) in the near future, as well as for other processes such as sepsis, acute kidney injury, inflammation, endothelial dysfunction, metabolic syndrome or, in diabetes, cardiovascular complications. However, no studies have been done using APs as a primary therapeutic target for clinical outcomes, and therefore, AP's levels cannot yet be used alone as an isolated primary target in the treatment of CKD-MBD. Nonetheless, its diagnostic and prognostic potential should be underlined.

Missed opportunities in primary care: the importance of identifying depression through screening, family history, and chronic disease management.

PubMed

Maradiegue, Ann H; Khan, Fakiha

2013-02-01

This study explored the adequacy of depression screening in a community health center. The medical charts of individuals (N = 90) enrolled at a community health center were randomly selected, reviewed, and compared to current standard-of-care guidelines for four elements: family history, screening for depression, control of chronic illnesses, and missed opportunities for preventive care. Family history documentation collected by the providers was limited and 44.4% had no family history. There was no routine depression screening process, although 48.9% of the clients had red flags (warning signals) for depression. Laboratory values used for screening control of chronic disease in the medical records were: fasting glucose levels ⩽100 mg/dL (46%), total cholesterol levels ⩽200 mg/dL (38%), and blood pressure ⩽120/80 mmHg (23%). The results highlight the need to focus on depression screening as part of preventive care and the management of chronic disease in the primary care setting. Copyright 2013, SLACK Incorporated.

Ferulic acid and its water-soluble derivatives inhibit nitric oxide production and inducible nitric oxide synthase expression in rat primary astrocytes.

PubMed

Kikugawa, Masaki; Ida, Tomoaki; Ihara, Hideshi; Sakamoto, Tatsuji

2017-08-01

We recently reported that two water-soluble derivatives of ferulic acid (1-feruloyl glycerol, 1-feruloyl diglycerol) previously developed by our group exhibited protective effects against amyloid-β-induced neurodegeneration in vitro and in vivo. In the current study, we aimed to further understand this process by examining the derivatives' ability to suppress abnormal activation of astrocytes, the key event of neurodegeneration. We investigated the effects of ferulic acid (FA) derivatives on nitric oxide (NO) production and inducible nitric oxide synthase (iNOS) expression in rat primary astrocytes. The results showed that these compounds inhibited NO production and iNOS expression in a concentration-dependent manner and that the mechanism underlying these effects was the suppression of the nuclear factor-κB pathway. This evidence suggests that FA and its derivatives may be effective neuroprotective agents and could be useful in the treatment of neurodegenerative diseases, such as Alzheimer's disease and Parkinson's disease.

Integrative Analysis of Disease Signatures Shows Inflammation Disrupts Juvenile Experience-Dependent Cortical Plasticity

PubMed Central

Smith, Milo R.; Burman, Poromendro

2016-01-01

Throughout childhood and adolescence, periods of heightened neuroplasticity are critical for the development of healthy brain function and behavior. Given the high prevalence of neurodevelopmental disorders, such as autism, identifying disruptors of developmental plasticity represents an essential step for developing strategies for prevention and intervention. Applying a novel computational approach that systematically assessed connections between 436 transcriptional signatures of disease and multiple signatures of neuroplasticity, we identified inflammation as a common pathological process central to a diverse set of diseases predicted to dysregulate plasticity signatures. We tested the hypothesis that inflammation disrupts developmental cortical plasticity in vivo using the mouse ocular dominance model of experience-dependent plasticity in primary visual cortex. We found that the administration of systemic lipopolysaccharide suppressed plasticity during juvenile critical period with accompanying transcriptional changes in a particular set of molecular regulators within primary visual cortex. These findings suggest that inflammation may have unrecognized adverse consequences on the postnatal developmental trajectory and indicate that treating inflammation may reduce the burden of neurodevelopmental disorders. PMID:28101530

The neck mass. 2. Inflammatory and neoplastic causes.

PubMed

Damion, J; Hybels, R L

1987-05-01

Several inflammatory processes can cause nodules or swelling in the neck. A complete physical examination and, usually, laboratory testing are required to establish the diagnosis. Common infections include cervical lymphadenitis and tuberculous lymphadenitis, cat-scratch disease, infection in the neck spaces, infectious mononucleosis, and syphilis. Primary or metastatic cancer may also be the cause. Cervical metastasis often presents as a neck mass. Although a primary tumor may not be found immediately when a neck mass is being evaluated, one is often discovered later. Other types of malignancy that may be present are histiocytic lymphoma, Hodgkin's disease, rhabdomyosarcoma, thyroid cancer, and a salivary (most often parotid) gland tumor. Symptomatic treatment is sometimes adequate for infectious disease, but administration of antituberculous drugs or antibiotics may also be necessary. Incision and drainage are required for some nodes and abscesses. For neck masses caused by neoplasms, fine-needle aspiration cytology or biopsy is performed. Depending on the diagnosis, treatment consists of dissection, radiation therapy, and/or chemotherapy.

Distinct patterns of brain activity evoked by histamine-induced itch reveal an association with itch intensity and disease severity in atopic dermatitis

PubMed Central

Ishiuji, Y.; Coghill, R.C.; Patel, T.S.; Oshiro, Y.; Kraft, R.A.; Yosipovitch, G.

2009-01-01

Summary Background Little is known about brain mechanisms supporting the experience of chronic puritus in disease states. Objectives To examine the difference in brain processing of histamine-induced itch in patients with active atopic dermatitis (AD) vs. healthy controls with the emerging technique of functional magnetic resonance imaging (fMRI) using arterial spin labelling (ASL). Methods Itch was induced with histamine iontophoresis in eight patients with AD and seven healthy subjects. Results We found significant differences in brain processing of histamine-induced itch between patients with AD and healthy subjects. Patients with AD exhibited bilateral activation of the anterior cingulate cortex (ACC), posterior cingulate cortex (PCC), retrosplenial cingulate cortex and dorsolateral prefrontal cortex (DLPFC) as well as contralateral activation of the caudate nucleus and putamen. In contrast, healthy subjects activated the primary motor cortex, primary somatosensory cortex and superior parietal lobe. The PCC and precuneus exhibited significantly greater activity in patients vs. healthy subjects. A significant correlation between percentage changes of brain activation was noted in the activation of the ACC and contralateral insula and histamine-induced itch intensity as well as disease severity in patients with AD. In addition, an association was noted between DLPFC activity and disease severity. Conclusions Our results demonstrate that ASL fMRI is a promising technique to assess brain activity in chronic itch. Brain activity of acute itch in AD seems to differ from that in healthy subjects. Moreover, the activity in cortical areas involved in affect and emotion correlated to measures of disease severity. PMID:19663870

Validation of a Natural Language Processing Algorithm for Detecting Infectious Disease Symptoms in Primary Care Electronic Medical Records in Singapore.

PubMed

Hardjojo, Antony; Gunachandran, Arunan; Pang, Long; Abdullah, Mohammed Ridzwan Bin; Wah, Win; Chong, Joash Wen Chen; Goh, Ee Hui; Teo, Sok Huang; Lim, Gilbert; Lee, Mong Li; Hsu, Wynne; Lee, Vernon; Chen, Mark I-Cheng; Wong, Franco; Phang, Jonathan Siung King

2018-06-11

Free-text clinical records provide a source of information that complements traditional disease surveillance. To electronically harness these records, they need to be transformed into codified fields by natural language processing algorithms. The aim of this study was to develop, train, and validate Clinical History Extractor for Syndromic Surveillance (CHESS), an natural language processing algorithm to extract clinical information from free-text primary care records. CHESS is a keyword-based natural language processing algorithm to extract 48 signs and symptoms suggesting respiratory infections, gastrointestinal infections, constitutional, as well as other signs and symptoms potentially associated with infectious diseases. The algorithm also captured the assertion status (affirmed, negated, or suspected) and symptom duration. Electronic medical records from the National Healthcare Group Polyclinics, a major public sector primary care provider in Singapore, were randomly extracted and manually reviewed by 2 human reviewers, with a third reviewer as the adjudicator. The algorithm was evaluated based on 1680 notes against the human-coded result as the reference standard, with half of the data used for training and the other half for validation. The symptoms most commonly present within the 1680 clinical records at the episode level were those typically present in respiratory infections such as cough (744/7703, 9.66%), sore throat (591/7703, 7.67%), rhinorrhea (552/7703, 7.17%), and fever (928/7703, 12.04%). At the episode level, CHESS had an overall performance of 96.7% precision and 97.6% recall on the training dataset and 96.0% precision and 93.1% recall on the validation dataset. Symptoms suggesting respiratory and gastrointestinal infections were all detected with more than 90% precision and recall. CHESS correctly assigned the assertion status in 97.3%, 97.9%, and 89.8% of affirmed, negated, and suspected signs and symptoms, respectively (97.6% overall accuracy). Symptom episode duration was correctly identified in 81.2% of records with known duration status. We have developed an natural language processing algorithm dubbed CHESS that achieves good performance in extracting signs and symptoms from primary care free-text clinical records. In addition to the presence of symptoms, our algorithm can also accurately distinguish affirmed, negated, and suspected assertion statuses and extract symptom durations. ©Antony Hardjojo, Arunan Gunachandran, Long Pang, Mohammed Ridzwan Bin Abdullah, Win Wah, Joash Wen Chen Chong, Ee Hui Goh, Sok Huang Teo, Gilbert Lim, Mong Li Lee, Wynne Hsu, Vernon Lee, Mark I-Cheng Chen, Franco Wong, Jonathan Siung King Phang. Originally published in JMIR Medical Informatics (http://medinform.jmir.org), 11.06.2018.

Financial Incentives for Chronic Disease Management: Results and Limitations of 2 Randomized Clinical Trials With New York Medicaid Patients.

PubMed

VanEpps, Eric M; Troxel, Andrea B; Villamil, Elizabeth; Saulsgiver, Kathryn A; Zhu, Jingsan; Chin, Jo-Yu; Matson, Jacqueline; Anarella, Joseph; Roohan, Patrick; Gesten, Foster; Volpp, Kevin G

2018-01-01

To identify whether financial incentives promote improved disease management in Medicaid recipients diagnosed with hypertension or diabetes, respectively. Four-group, multicenter, randomized clinical trials. Between 2013 and 2016, New York State Medicaid managed care members diagnosed with hypertension (N = 920) or with diabetes (N = 959). Participants in each 6-month trial were randomly assigned to 1 of 4 arms: (1) process incentives-earned by attending primary care visits and/or receiving prescription medication refills, (2) outcome incentives-earned by reducing systolic blood pressure (hypertension) or hemoglobin A 1c (HbA 1c ; diabetes) levels, (3) combined process and outcome incentives, and (4) control (no incentives). Systolic blood pressure (hypertension) and HbA 1c (diabetes) levels, primary care visits, and medication prescription refills. Analysis and Results: At 6 months, there were no statistically significant differences between intervention arms and the control arm in the change in systolic blood pressure, P = .531. Similarly, there were no significant differences in blood glucose control (HbA 1c ) between the intervention arms and control after 6 months, P = .939. The majority of participants had acceptable systolic blood pressure (<140 mm Hg) or blood glucose (<8.0%) levels at baseline and throughout the study. Financial incentives-regardless of whether they were delivered based on disease-relevant outcomes, process activities, or a combination of the two-have a negligible impact on health outcomes for Medicaid recipients diagnosed with either hypertension or diabetes in 2 studies in which, among other design and operational limitations, the majority of recipients had relatively well-controlled diseases at the time of enrollment.

Review of behavioral health integration in primary care at Baylor Scott and White Healthcare, Central Region

PubMed Central

Fluet, Norman R.; Reis, Michael D.; Stern, Charles H.; Thompson, Alexander W.; Jolly, Gillian A.

2016-01-01

The integration of behavioral health services in primary care has been referred to in many ways, but ultimately refers to common structures and processes. Behavioral health is integrated into primary care because it increases the effectiveness and efficiency of providing care and reduces costs in the care of primary care patients. Reimbursement is one factor, if not the main factor, that determines the level of integration that can be achieved. The federal health reform agenda supports changes that will eventually permit behavioral health to be fully integrated and will allow the health of the population to be the primary target of intervention. In an effort to develop more integrated services at Baylor Scott and White Healthcare, models of integration are reviewed and the advantages and disadvantages of each model are discussed. Recommendations to increase integration include adopting a disease management model with care management, planned guideline-based stepped care, follow-up, and treatment monitoring. Population-based interventions can be completed at the pace of the development of alternative reimbursement methods. The program should be based upon patient-centered medical home standards, and research is needed throughout the program development process. PMID:27034543

Live-Cell Imaging of Phagosome Motility in Primary Mouse RPE Cells.

PubMed

Hazim, Roni; Jiang, Mei; Esteve-Rudd, Julian; Diemer, Tanja; Lopes, Vanda S; Williams, David S

2016-01-01

The retinal pigment epithelium (RPE) is a post-mitotic epithelial monolayer situated between the light-sensitive photoreceptors and the choriocapillaris. Given its vital functions for healthy vision, the RPE is a primary target for insults that result in blinding diseases, including age-related macular degeneration (AMD). One such function is the phagocytosis and digestion of shed photoreceptor outer segments. In the present study, we examined the process of trafficking of outer segment disk membranes in live cultures of primary mouse RPE, using high speed spinning disk confocal microscopy. This approach has enabled us to track phagosomes, and determine parameters of their motility, which are important for their efficient degradation.

Better health outcomes at lower costs: the benefits of primary care utilisation for chronic disease management in remote Indigenous communities in Australia's Northern Territory.

PubMed

Zhao, Yuejen; Thomas, Susan L; Guthridge, Steven L; Wakerman, John

2014-10-04

Indigenous residents living in remote communities in Australia's Northern Territory experience higher rates of preventable chronic disease and have poorer access to appropriate health services compared to other Australians. This study compared health outcomes and costs at different levels of primary care utilisation to determine if primary care represents an efficient use of resources for Indigenous patients with common chronic diseases namely hypertension, diabetes, ischaemic heart disease, chronic obstructive pulmonary disease and renal disease. This was an historical cohort study involving a total of 14,184 Indigenous residents, aged 15 years and over, who lived in remote communities and used a remote clinic or public hospital from 2002 to 2011. Individual level demographic and clinical data were drawn from primary care and hospital care information systems using a unique patient identifier. A propensity score was used to improve comparability between high, medium and low primary care utilisation groups. Incremental cost-effectiveness ratios and acceptability curves were used to analyse four health outcome measures: total and, avoidable hospital admissions, deaths and years of life lost. Compared to the low utilisation group, medium and high levels of primary care utilisation were associated with decreases in total and avoidable hospitalisations, deaths and years of life lost. Higher levels of primary care utilisation for renal disease reduced avoidable hospitalisations by 82-85%, deaths 72-75%, and years of life lost 78-81%. For patients with ischaemic heart disease, the reduction in avoidable hospitalisations was 63-78%, deaths 63-66% and years of life lost 69-73%. In terms of cost-effectiveness, primary care for renal disease and diabetes ranked as more cost-effective, followed by hypertension and ischaemic heart disease. Primary care for chronic obstructive pulmonary disease was the least cost-effective of the five conditions. Primary care in remote Indigenous communities was shown to be associated with cost-savings to public hospitals and health benefits to individual patients. Investing $1 in primary care in remote Indigenous communities could save $3.95-$11.75 in hospital costs, in addition to health benefits for individual patients. These findings may have wider applicability in strengthening primary care in the face of high chronic disease prevalence globally.

Silvicultural applications: Restoring ecological structure and process in ponderosa pine forests

Treesearch

Carl E. Fiedler

1996-01-01

A primary goal of restoration treatments in ponderosa pine (Pinus ponderosa)/fir forests is to create more open stand structures, thereby improving tree vigor and reducing vulnerability to insects, disease, and severe fire. An additional goal in some stands is to manipulate existing species composition and site conditions to favor regeneration of...

[Persistent diarrhea in the returned traveler].

PubMed

de Saussure, P; Hadengue, A

2006-05-10

Persistent diarrhea in a returned traveler is a frequent presenting complaint and may result from three etiologic groups: persistant infections, non-infectious post-gastroenteritis processes (in particular postinfectious irritable bowel syndrome) and appearance of an unrelated cause of chronic diarrhea. This article reviews the most frequent diseases involved and provides management guidelines for primary care physicians.

Dietary primary prevention of allergic diseases in children: the Philippine guidelines

PubMed Central

Recto, Marysia Stella T.; Genuino, Maria Lourdes G.; Casis-Hao, Roxanne J.; Tamondong-Lachica, Diana R.; Sales, Maria Imelda V.; Tan, Marilou G.; Mondonedo, Karen S.; Dionisio-Capulong, Regina C.

2017-01-01

Allergic diseases, such as asthma, allergic rhinitis, eczema, and food allergy, are preventable diseases. Primary prevention strategies of allergic diseases have been in scrutiny. Effective prevention strategies maybe started prenatally, postnatally, during infancy, and even during childhood. These guidelines have been prepared by the Philippine Society of Allergy, Asthma and Immunology and the Philippine Society for Pediatric Gastroenterology, Hepatology and Nutrition. They aim to provide evidence-based recommendations for the dietary primary prevention of allergic diseases in children. The primary audience of these guidelines is all healthcare practitioners who manage patients with potential allergic conditions. These guidelines are based on an exhaustive review of evidences, mostly systematic reviews, randomized controlled trials, and cohort studies. However, there are still many gaps in the evidence of dietary primary prevention of allergic diseases. PMID:28487842

Learning How Scientists Work: Experiential Research Projects to Promote Cell Biology Learning and Scientific Process Skills

PubMed Central

2002-01-01

Facilitating not only the mastery of sophisticated subject matter, but also the development of process skills is an ongoing challenge in teaching any introductory undergraduate course. To accomplish this goal in a sophomore-level introductory cell biology course, I require students to work in groups and complete several mock experiential research projects that imitate the professional activities of the scientific community. I designed these projects as a way to promote process skill development within content-rich pedagogy and to connect text-based and laboratory-based learning with the world of contemporary research. First, students become familiar with one primary article from a leading peer-reviewed journal, which they discuss by means of PowerPoint-based journal clubs and journalism reports highlighting public relevance. Second, relying mostly on primary articles, they investigate the molecular basis of a disease, compose reviews for an in-house journal, and present seminars in a public symposium. Last, students author primary articles detailing investigative experiments conducted in the lab. This curriculum has been successful in both quarter-based and semester-based institutions. Student attitudes toward their learning were assessed quantitatively with course surveys. Students consistently reported that these projects significantly lowered barriers to primary literature, improved research-associated skills, strengthened traditional pedagogy, and helped accomplish course objectives. Such approaches are widely suited for instructors seeking to integrate process with content in their courses. PMID:12669101

Learning how scientists work: experiential research projects to promote cell biology learning and scientific process skills.

PubMed

DebBurman, Shubhik K

2002-01-01

Facilitating not only the mastery of sophisticated subject matter, but also the development of process skills is an ongoing challenge in teaching any introductory undergraduate course. To accomplish this goal in a sophomore-level introductory cell biology course, I require students to work in groups and complete several mock experiential research projects that imitate the professional activities of the scientific community. I designed these projects as a way to promote process skill development within content-rich pedagogy and to connect text-based and laboratory-based learning with the world of contemporary research. First, students become familiar with one primary article from a leading peer-reviewed journal, which they discuss by means of PowerPoint-based journal clubs and journalism reports highlighting public relevance. Second, relying mostly on primary articles, they investigate the molecular basis of a disease, compose reviews for an in-house journal, and present seminars in a public symposium. Last, students author primary articles detailing investigative experiments conducted in the lab. This curriculum has been successful in both quarter-based and semester-based institutions. Student attitudes toward their learning were assessed quantitatively with course surveys. Students consistently reported that these projects significantly lowered barriers to primary literature, improved research-associated skills, strengthened traditional pedagogy, and helped accomplish course objectives. Such approaches are widely suited for instructors seeking to integrate process with content in their courses.

Development and Validation of a Questionnaire to Assess Multimorbidity in Primary Care: An Indian Experience.

PubMed

Pati, Sanghamitra; Hussain, Mohammad Akhtar; Swain, Subhashisa; Salisbury, Chris; Metsemakers, Job F M; Knottnerus, J André; van den Akker, Marjan

2016-01-01

Multimorbidity remains an underexplored domain in Indian primary care. We undertook a study to assess the prevalence, correlates, and outcomes of multimorbidity in primary care settings in India. This paper describes the process of development and validation of our data collection tool "Multimorbidity Assessment Questionnaire for Primary Care (MAQ-PC)." An iterative process comprising desk review, chart review, and expert consultations was undertaken to generate the questionnaire. The MAQ-PC contained items on chronic conditions, health care utilization, health related quality of life, disease severity, and sociodemographics. It was first tested with twelve adults for comprehensibility followed by test-retest reliability with 103 patients from four primary care practices. For interrater reliability, two interviewers separately administered the questionnaire to sixteen patients. MAQ-PC displayed strong internal consistency (Cronbach's alpha: 0.69), interrater reliability (Cohen's Kappa: 0.78-1), and test-retest reliability (ICC: 0.970-0.741). Substantial concordance between self-report and physician diagnosis (Scott Kappa: 0.59-1.0) was observed for listed chronic conditions indicating strong concurrent validity. Nearly 54% had one chronic condition and 23.3% had multimorbidity. Our findings demonstrate MAQ-PC to be a valid and reliable measure of multimorbidity in primary care practice and suggest its potential utility in multimorbidity research in India.

Sporadic Jakob-Creutzfeldt Disease Presenting as Primary Progressive Aphasia

PubMed Central

Johnson, David Y.; Dunkelberger, Diana L.; Henry, Maya; Haman, Aissatou; Greicius, Michael D.; Wong, Katherine; DeArmond, Stephen J.; Miller, Bruce L.; Gorno-Tempini, Maria Luisa; Geschwind, Michael D.

2015-01-01

Objective To report the clinical, neuropsychological, linguistic, imaging, and neuropathological features of a unique case of sporadic Jakob-Creutzfeldt disease in which the patient presented with a logopenic variant of primary progressive aphasia. Design Case report. Setting Large referral center for atypical memory and aging disorders, particularly Jakob-Creutzfeldt disease. Patient Patient presenting with logopenic variant primary progressive aphasia initially thought to be due to Alzheimer disease. Results Despite the long, slow 3.5-year course, the patient was shown to have pathology-proven sporadic Jakob-Creutzfeldt disease. Conclusions These findings expand the differential of primary progressive aphasia to include prion disease. PMID:23400721

THE COURSE OF A SMALLPOX VACCINAL PROCESS AND THE FORMATION OF ANTISMALLPOX IMMUNITY IN RABBITS DUE TO THE EFFECT OF X IRRADIATION (in Russian)

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

Kamalyan, L.A.

1961-01-01

A study of vaccination process peculiarities in rabbits, previously irradiated with an x-ray dose of 700 r, shows that the course of the process grows worse, the duration of the locai reaction becomes longer, the disease spreads and some of the animals die. A repeated infection of the rabbits (cutaneous and cerebral) shows that the intensity of antismallpox immunity is lower in irradiated animals than in nonirradiated ones in the case of primary and secondary immurization. A total irradiation suppresses the process of hemagglutination. (auth)

Work Process in Primary Health Care: action research with Community Health Workers.

PubMed

Cordeiro, Luciana; Soares, Cassia Baldini

2015-11-01

The aim of this article was to describe and analyze the work of community health workers (CHW). The main objective of study was to analyze the development process of primary health care practices related to drug consumption. The study is based on the Marxist theoretical orientation and the action research methodology, which resulted in the performance of 15 emancipatory workshops. The category work process spawned the content analysis. It exposed the social abandonment of the environment in which the CHWs work is performed. The latter had an essential impact on the identification of the causes of drug-related problems. These findings made it possible to criticize the reiterative, stressful actions that are being undertaken there. Such an act resulted in raising of the awareness and creating the means for political action. The CHWs motivated themselves to recognize the object of the work process in primary health care, which they found to be the disease or addiction in the case of drug users. They have criticized this categorization as well as discussed the social division of work and the work itself whilst recognizing themselves as mere instruments in the work process. The latter has inspired the CHW to become subjects, or co-producers of transformations of social needs.

Nutrition in primary health care: using a Delphi process to design new interdisciplinary services.

PubMed

Brauer, Paula; Dietrich, Linda; Davidson, Bridget

2006-01-01

A modified Delphi process was used to identify key features of interdisciplinary nutrition services, including provider roles and responsibilities for Ontario Family Health Networks (FHNs), a family physician-based type of primary care. Twenty-three representatives from interested professional organizations, including three FHN demonstration sites, completed a modified Delphi process. Participants reviewed evidence from a systematic literature review, a patient survey, a costing analysis, and key informant interview results before undertaking the Delphi process. Statements describing various options for services were developed at an in-person meeting, which was followed by two rounds of e-mail questionnaires. Teleconference discussions were held between rounds. An interdisciplinary model with differing and complementary roles for health care providers emerged from the process. Additional key features addressing screening for nutrition problems, health promotion and disease prevention, team collaboration, planning and evaluation, administrative support, access to care, and medical directives/delegated acts were identified. Under the proposed model, the registered dietitian is the team member responsible for managing all aspects of nutrition services, from needs assessment to program delivery, as well as for supporting all providers' nutrition services. The proposed interdisciplinary nutrition services model merits evaluation of cost, effectiveness, applicability, and sustainability in team-based primary care service settings.

Do Independent Sector Treatment Centres (ISTC) Impact on Specialist Registrar Training in Primary Hip and Knee Arthroplasty?

PubMed Central

Clamp, Jonathan A; Baiju, Dean SR; Copas, David P; Hutchinson, James W; Rowles, John M

2008-01-01

INTRODUCTION The introduction of Modernising Medical Careers (MMC) is likely to reduce specialist registrar (SpR) operative experience during higher surgical training (HST). A further negative impact on training by local Independent Sector Treatment Centres (ISTCs) could reduce experience, and thus competence, in primary joint arthroplasty at completion of higher surgical training. PATIENTS AND METHODS Retrospective case note and radiograph analysis of patients receiving primary hip and knee arthroplasty in a teaching hospital, before and after the establishment of a local ISTC. Patients and operative details were recorded from the selected case notes. Corresponding radiographs were assessed and the severity of the disease process assessed. RESULTS Fewer primary hip and knee replacements were performed by SpRs in the time period after the establishment of an ISTC. Conclusions ISTCs may adversely affect SpR training in primary joint arthroplasty. PMID:18765029

Information system support as a critical success factor for chronic disease management: Necessary but not sufficient.

PubMed

Green, Carolyn J; Fortin, Patricia; Maclure, Malcolm; Macgregor, Art; Robinson, Sylvia

2006-12-01

Improvement of chronic disease management in primary care entails monitoring indicators of quality over time and across patients and practices. Informatics tools are needed, yet implementing them remains challenging. To identify critical success factors enabling the translation of clinical and operational knowledge about effective and efficient chronic care management into primary care practice. A prospective case study of positive deviants using key informant interviews, process observation, and document review. A chronic disease management (CDM) collaborative of primary care physicians with documented improvement in adherence to clinical practice guidelines using a web-based patient registry system with CDM guideline-based flow sheet. Thirty community-based physician participants using predominantly paper records, plus a project management team including the physician lead, project manager, evaluator and support team. A critical success factor (CSF) analysis of necessary and sufficient pathways to the translation of knowledge into clinical practice. A web-based CDM 'toolkit' was found to be a direct CSF that allowed this group of physicians to improve their practice by tracking patient care processes using evidence-based clinical practice guideline-based flow sheets. Moreover, the information and communication technology 'factor' was sufficient for success only as part of a set of seven direct CSF components including: health delivery system enhancements, organizational partnerships, funding mechanisms, project management, practice models, and formal knowledge translation practices. Indirect factors that orchestrated success through the direct factor components were also identified. A central insight of this analysis is that a comprehensive quality improvement model was the CSF that drew this set of factors into a functional framework for successful knowledge translation. In complex primary care settings environment where physicians have low adoption rates of electronic tools to support the care of patients with chronic conditions, successful implementation may require a set of interrelated system and technology factors.

Implementing Quality Improvement in Small, Autonomous Primary Care Practices: Implications for the Patient Centered Medical Home

PubMed Central

Arar, Nedal H.; Noel, Polly H.; Leykum, Luci; Zeber, John E.; Romero, Raquel; Parchman, Michael L.

2012-01-01

Background Implementing improvement programs to enhance quality of care within primary care clinics is complex, with limited practical guidance available to help practices during the process. Understanding how improvement strategies can be implemented in primary care is timely given the recent national movement towards transforming primary care into patient-centered medical homes (PCMH). This study examined practice members’ perceptions of the opportunities and challenges associated with implementing changes in their practice. Methods Semi-structured interviews were conducted with a purposive sample of 56 individuals working in 16 small, community-based primary care practices. The interview consisted of open-ended questions focused on participants’ perceptions of: (1) practice vision, (2) perceived need for practice improvement, and (3) barriers that hinder practice improvement. The interviews were conducted at the participating clinics and were tape-recorded, transcribed, and content analyzed. Results Content analysis identified two main domains for practice improvement related to: (1) the process of care, and (2) patients’ involvement in their disease management. Examples of desired process of care changes included improvement in patient tracking/follow-up system, standardization of processes of care, and overall clinic documentations. Changes related to the patients’ involvement in their care included improving (a) health education, and (b) self care management. Among the internal barriers were: staff readiness for change, poor communication, and relationship difficulties among team members. External barriers were: insurance regulations, finances and patient health literacy. Practice Implications Transforming their practices to more patient-centered models of care will be a priority for primary care providers. Identifying opportunities and challenges associated with implementing change is critical for successful improvement programs. Successful strategy for enhancing the adoption and uptake of PCMH elements should leverage areas of concordance between practice members’ perceived needs and planned improvement efforts. PMID:22186171

Mathematical Modeling of Protein Misfolding Mechanisms in Neurological Diseases: A Historical Overview.

PubMed

Carbonell, Felix; Iturria-Medina, Yasser; Evans, Alan C

2018-01-01

Protein misfolding refers to a process where proteins become structurally abnormal and lose their specific 3-dimensional spatial configuration. The histopathological presence of misfolded protein (MP) aggregates has been associated as the primary evidence of multiple neurological diseases, including Prion diseases, Alzheimer's disease, Parkinson's disease, and Creutzfeldt-Jacob disease. However, the exact mechanisms of MP aggregation and propagation, as well as their impact in the long-term patient's clinical condition are still not well understood. With this aim, a variety of mathematical models has been proposed for a better insight into the kinetic rate laws that govern the microscopic processes of protein aggregation. Complementary, another class of large-scale models rely on modern molecular imaging techniques for describing the phenomenological effects of MP propagation over the whole brain. Unfortunately, those neuroimaging-based studies do not take full advantage of the tremendous capabilities offered by the chemical kinetics modeling approach. Actually, it has been barely acknowledged that the vast majority of large-scale models have foundations on previous mathematical approaches that describe the chemical kinetics of protein replication and propagation. The purpose of the current manuscript is to present a historical review about the development of mathematical models for describing both microscopic processes that occur during the MP aggregation and large-scale events that characterize the progression of neurodegenerative MP-mediated diseases.

Vitamin, Mineral, and Multivitamin Supplements for the Primary Prevention of Cardiovascular Disease and Cancer

MedlinePlus

... and Multivitamin Supplements for the Primary Prevention of Cardiovascular Disease and Cancer The U.S. Preventive Services Task Force ( ... and Multivitamin Supplements for the Primary Prevention of Cardiovascular Disease and Cancer. This final recommendation statement applies to ...

Systematic age-related differences in chronic disease management in a population-based cohort study: a new paradigm of primary care is required.

PubMed

Buja, Alessandra; Damiani, Gianfranco; Gini, Rosa; Visca, Modesta; Federico, Bruno; Donato, Daniele; Francesconi, Paolo; Marini, Alessandro; Donatini, Andrea; Brugaletta, Salvatore; Baldo, Vincenzo; Donata Bellentani, Maria

2014-01-01

Our interest in chronic conditions is due to the fact that, worldwide, chronic diseases have overtaken infectious diseases as the leading cause of death and disability, so their management represents an important challenge for health systems. The aim of this study was to compare the performance of primary health care services in managing diabetes, congestive heart failure (CHF) and coronary heart disease (CHD), by age group. This population-based retrospective cohort study was conducted in Italy, enrolling 1,948,622 residents ≥ 16 years old. A multilevel regression model was applied to analyze compliance to care processes with explanatory variables at both patient and district level, using age group as an independent variable, and adjusting for sex, citizenship, disease duration, and Charlson index on the first level, and for District Health Unit on the second level. The quality of chronic disease management showed an inverted U-shaped relationship with age. In particular, our findings indicate lower levels for young adults (16-44 year-olds), adults (45-64), and oldest old (+85) than for patients aged 65-74 in almost all quality indicators of CHD, CHF and diabetes management. Young adults (16-44 y), adults (45-64 y), the very old (75-84 y) and the oldest old (+85 y) patients with CHD, CHF and diabetes are less likely than 65-74 year-old patients to be monitored and treated using evidence-based therapies, with the exceptions of echocardiographic monitoring for CHF in young adult patients, and renal monitoring for CHF and diabetes in the very old. Our study shows that more effort is needed to ensure that primary health care systems are sensitive to chronic conditions in the young and in the very elderly.

Clinical practice guidelines within the Southern African development community: a descriptive study of the quality of guideline development and concordance with best evidence for five priority diseases

PubMed Central

2012-01-01

Background Reducing the burden of disease relies on availability of evidence-based clinical practice guidelines (CPGs). There is limited data on availability, quality and content of guidelines within the Southern African Development Community (SADC). This evaluation aims to address this gap in knowledge and provide recommendations for regional guideline development. Methods We prioritised five diseases: HIV in adults, malaria in children and adults, pre-eclampsia, diarrhoea in children and hypertension in primary care. A comprehensive electronic search to locate guidelines was conducted between June and October 2010 and augmented with email contact with SADC Ministries of Health. Independent reviewers used the AGREE II tool to score six quality domains reporting the guideline development process. Alignment of the evidence-base of the guidelines was evaluated by comparing their content with key recommendations from accepted reference guidelines, identified with a content expert, and percentage scores were calculated. Findings We identified 30 guidelines from 13 countries, publication dates ranging from 2003-2010. Overall the 'scope and purpose' and 'clarity and presentation' domains of the AGREE II instrument scored highest, median 58%(range 19-92) and 83%(range 17-100) respectively. 'Stakeholder involvement' followed with median 39%(range 6-75). 'Applicability', 'rigour of development' and 'editorial independence' scored poorly, all below 25%. Alignment with evidence was variable across member states, the lowest scores occurring in older guidelines or where the guideline being evaluated was part of broader primary healthcare CPG rather than a disease-specific guideline. Conclusion This review identified quality gaps and variable alignment with best evidence in available guidelines within SADC for five priority diseases. Future guideline development processes within SADC should better adhere to global reporting norms requiring broader consultation of stakeholders and transparency of process. A regional guideline support committee could harness local capacity to support context appropriate guideline development. PMID:22221856

Protection of primary neurons and mouse brain from Alzheimer’s pathology by molecular tweezers

PubMed Central

Attar, Aida; Ripoli, Cristian; Riccardi, Elisa; Maiti, Panchanan; Li Puma, Domenica D.; Liu, Tingyu; Hayes, Jane; Jones, Mychica R.; Lichti-Kaiser, Kristin; Yang, Fusheng; Gale, Greg D.; Tseng, Chi-hong; Tan, Miao; Xie, Cui-Wei; Straudinger, Jeffrey L.; Klärner, Frank-Gerrit; Schrader, Thomas; Frautschy, Sally A.; Grassi, Claudio

2012-01-01

Alzheimer’s disease is a devastating cureless neurodegenerative disorder affecting >35 million people worldwide. The disease is caused by toxic oligomers and aggregates of amyloid β protein and the microtubule-associated protein tau. Recently, the Lys-specific molecular tweezer CLR01 has been shown to inhibit aggregation and toxicity of multiple amyloidogenic proteins, including amyloid β protein and tau, by disrupting key interactions involved in the assembly process. Following up on these encouraging findings, here, we asked whether CLR01 could protect primary neurons from Alzheimer’s disease-associated synaptotoxicity and reduce Alzheimer’s disease–like pathology in vivo. Using cell culture and brain slices, we found that CLR01 effectively inhibited synaptotoxicity induced by the 42-residue isoform of amyloid β protein, including ∼80% inhibition of changes in dendritic spines density and long-term potentiation and complete inhibition of changes in basal synaptic activity. Using a radiolabelled version of the compound, we found that CLR01 crossed the mouse blood–brain barrier at ∼2% of blood levels. Treatment of 15-month-old triple-transgenic mice for 1 month with CLR01 resulted in a decrease in brain amyloid β protein aggregates, hyperphosphorylated tau and microglia load as observed by immunohistochemistry. Importantly, no signs of toxicity were observed in the treated mice, and CLR01 treatment did not affect the amyloidogenic processing of amyloid β protein precursor. Examining induction or inhibition of the cytochrome P450 metabolism system by CLR01 revealed minimal interaction. Together, these data suggest that CLR01 is safe for use at concentrations well above those showing efficacy in mice. The efficacy and toxicity results support a process-specific mechanism of action of molecular tweezers and suggest that these are promising compounds for developing disease-modifying therapy for Alzheimer’s disease and related disorders. PMID:23183235

Primary care clinicians' experiences with treatment decision making for older persons with multiple conditions.

PubMed

Fried, Terri R; Tinetti, Mary E; Iannone, Lynne

2011-01-10

Clinicians are caring for an increasing number of older patients with multiple diseases in the face of uncertainty concerning the benefits and harms associated with guideline-directed interventions. Understanding how primary care clinicians approach treatment decision making for these patients is critical to the design of interventions to improve the decision-making process. Focus groups were conducted with 40 primary care clinicians (physicians, nurse practitioners, and physician assistants) in academic, community, and Veterans Affairs-affiliated primary care practices. Participants were given open-ended questions about their approach to treatment decision making for older persons with multiple medical conditions. Responses were organized into themes using qualitative content analysis. The participants were concerned about their patients' ability to adhere to complex regimens derived from guideline-directed care. There was variability in beliefs regarding, and approaches to balancing, the benefits and harms of guideline-directed care. There was also variability regarding how the participants involved patients in the process of decision making, with clinicians describing conflicts between their own and their patients' goals. The participants listed a number of barriers to making good treatment decisions, including the lack of outcome data, the role of specialists, patient and family expectations, and insufficient time and reimbursement. The experiences of practicing clinicians suggest that they struggle with the uncertainties of applying disease-specific guidelines to their older patients with multiple conditions. To improve decision making, they need more data, alternative guidelines, approaches to reconciling their own and their patients' priorities, the support of their subspecialist colleagues, and an altered reimbursement system.

Cholesterol catalyses Aβ42 aggregation through a heterogeneous nucleation pathway in the presence of lipid membranes

NASA Astrophysics Data System (ADS)

Habchi, Johnny; Chia, Sean; Galvagnion, Céline; Michaels, Thomas C. T.; Bellaiche, Mathias M. J.; Ruggeri, Francesco Simone; Sanguanini, Michele; Idini, Ilaria; Kumita, Janet R.; Sparr, Emma; Linse, Sara; Dobson, Christopher M.; Knowles, Tuomas P. J.; Vendruscolo, Michele

2018-06-01

Alzheimer's disease is a neurodegenerative disorder associated with the aberrant aggregation of the amyloid-β peptide. Although increasing evidence implicates cholesterol in the pathogenesis of Alzheimer's disease, the detailed mechanistic link between this lipid molecule and the disease process remains to be fully established. To address this problem, we adopt a kinetics-based strategy that reveals a specific catalytic role of cholesterol in the aggregation of Aβ42 (the 42-residue form of the amyloid-β peptide). More specifically, we demonstrate that lipid membranes containing cholesterol promote Aβ42 aggregation by enhancing its primary nucleation rate by up to 20-fold through a heterogeneous nucleation pathway. We further show that this process occurs as a result of cooperativity in the interaction of multiple cholesterol molecules with Aβ42. These results identify a specific microscopic pathway by which cholesterol dramatically enhances the onset of Aβ42 aggregation, thereby helping rationalize the link between Alzheimer's disease and the impairment of cholesterol homeostasis.

Prediction of Disease Case Severity Level To Determine INA CBGs Rate

NASA Astrophysics Data System (ADS)

Puspitorini, Sukma; Kusumadewi, Sri; Rosita, Linda

2017-03-01

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

Is Helicobacter pylori Infection the Primary Cause of Duodenal Ulceration or a Secondary Factor? A Review of the Evidence

PubMed Central

Ananthakrishnan, N.; Tovey, Frank I.

2013-01-01

Helicobacter pylori (H. pylori) has a role in the multifactorial etiology of peptic ulcer disease. A link between H. pylori infection and duodenal ulcer disease is now established. Other contributing factors and their interaction with the organism may initiate the ulcerative process. The fact that eradication of H. pylori infection leads to a long-term cure in the majority of duodenal ulcer patients and the fact that the prevalence of infection is higher in ulcer patients than in the normal population are cogent arguments in favor of it being the primary cause of the ulceration. Against this concept there are issues that need explanation such as the reason why only a minority of infected persons develop duodenal ulceration when infection with H. pylori is widespread. There is evidence that H. pylori infection has been prevalent for several centuries, yet duodenal ulceration became common at the beginning of the twentieth century. The prevalence of duodenal ulceration is not higher in countries with a high prevalence of H. pylori infection. This paper debate puts forth the point of view of two groups of workers in this field whether H. pylori infection is the primary cause of duodenal ulcer disease or a secondary factor. PMID:23606834

Is Primary Prostate Cancer Treatment Influenced by Likelihood of Extraprostatic Disease? A Surveillance, Epidemiology and End Results Patterns of Care Study

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

Holmes, Jordan A.; Wang, Andrew Z.; University of North Carolina-Lineberger Comprehensive Cancer Center, Chapel Hill, NC

2012-09-01

Purpose: To examine the patterns of primary treatment in a recent population-based cohort of prostate cancer patients, stratified by the likelihood of extraprostatic cancer as predicted by disease characteristics available at diagnosis. Methods and Materials: A total of 157,371 patients diagnosed from 2004 to 2008 with clinically localized and potentially curable (node-negative, nonmetastatic) prostate cancer, who have complete information on prostate-specific antigen, Gleason score, and clinical stage, were included. Patients with clinical T1/T2 disease were grouped into categories of <25%, 25%-50%, and >50% likelihood of having extraprostatic disease using the Partin nomogram. Clinical T3/T4 patients were examined separately as themore » highest-risk group. Logistic regression was used to examine the association between patient group and receipt of each primary treatment, adjusting for age, race, year of diagnosis, marital status, Surveillance, Epidemiology and End Results database region, and county-level education. Separate models were constructed for primary surgery, external-beam radiotherapy (RT), and conservative management. Results: On multivariable analysis, increasing likelihood of extraprostatic disease was significantly associated with increasing use of RT and decreased conservative management. Use of surgery also increased. Patients with >50% likelihood of extraprostatic cancer had almost twice the odds of receiving prostatectomy as those with <25% likelihood, and T3-T4 patients had 18% higher odds. Prostatectomy use increased in recent years. Patients aged 76-80 years were likely to be managed conservatively, even those with a >50% likelihood of extraprostatic cancer (34%) and clinical T3-T4 disease (24%). The proportion of patients who received prostatectomy or conservative management was approximately 50% or slightly higher in all groups. Conclusions: There may be underutilization of RT in older prostate cancer patients and those with likely extraprostatic disease. Because more than half of prostate cancer patients do not consult with a radiation oncologist, a multidisciplinary consultation may affect the treatment decision-making process.« less

Mitochondrial Dynamics in Mitochondrial Diseases

PubMed Central

Suárez-Rivero, Juan M.; Villanueva-Paz, Marina; de la Cruz-Ojeda, Patricia; de la Mata, Mario; Cotán, David; Oropesa-Ávila, Manuel; de Lavera, Isabel; Álvarez-Córdoba, Mónica; Luzón-Hidalgo, Raquel; Sánchez-Alcázar, José A.

2016-01-01

Mitochondria are very versatile organelles in continuous fusion and fission processes in response to various cellular signals. Mitochondrial dynamics, including mitochondrial fission/fusion, movements and turnover, are essential for the mitochondrial network quality control. Alterations in mitochondrial dynamics can cause neuropathies such as Charcot-Marie-Tooth disease in which mitochondrial fusion and transport are impaired, or dominant optic atrophy which is caused by a reduced mitochondrial fusion. On the other hand, mitochondrial dysfunction in primary mitochondrial diseases promotes reactive oxygen species production that impairs its own function and dynamics, causing a continuous vicious cycle that aggravates the pathological phenotype. Mitochondrial dynamics provides a new way to understand the pathophysiology of mitochondrial disorders and other diseases related to mitochondria dysfunction such as diabetes, heart failure, or Hungtinton’s disease. The knowledge about mitochondrial dynamics also offers new therapeutics targets in mitochondrial diseases. PMID:28933354

Liquid Nitrogen Cryotherapy for Surface Eye Disease (An AOS Thesis)

PubMed Central

Fraunfelder, Frederick Web

2008-01-01

Purpose To evaluate the effects of new treatments with liquid nitrogen cryotherapy on some external eye conditions. Methods In this retrospective case study, 6 separate series from a single tertiary care referral center practice are described. Liquid nitrogen cryotherapy was used to treat conjunctival amyloidosis, primary pterygia, recurrent pterygia, advancing wavelike epitheliopathy (AWLE), superior limbic keratoconjunctivitis (SLK), and palpebral vernal keratoconjunctivitis (VKC). The main outcome measure was the resolution of the disease process after treatment. Results Four patients with primary localized conjunctival amyloidosis were treated with liquid nitrogen cryotherapy. Two of them had recurrence of the amyloidosis, which cleared with subsequent treatment. Eighteen patients with primary pterygia had excision and cryotherapy with 1 recurrence. Of 6 subjects who presented with recurrent pterygia, 4 had a second recurrence after excision and cryotherapy. In 5 patients with AWLE, the condition resolved within 2 weeks without recurrence or the need for subsequent cryotherapy. Four patients with SLK were treated with liquid nitrogen cryotherapy. Disease recurred in 2 patients and 3 of 7 eyes, although subsequent cryotherapy eradicated SLK in all cases. Two patients and 3 eyelids with palpebral VKC were treated with liquid nitrogen cryotherapy. VKC recurred in all cases. Conclusions Liquid nitrogen cryotherapy to the surface of the eye is effective in treating AWLE, and SLK. Excision followed by cryotherapy is successful in treating conjunctival amyloidosis and primary pterygia Liquid nitrogen cryotherapy is unsuccessful in the treatment of recurrent pterygia and VKC. PMID:19277243

Development of a family nursing model for prevention of cancer and other noncommunicable diseases through an appreciative inquiry.

PubMed

Jongudomkarn, Darunee; Macduff, Colin

2014-01-01

Cancer and non-communicable diseases are a major issue not only for the developed but also developing countries. Public health and primary care nursing offer great potential for primary and secondary prevention of these diseases through community and family-based approaches. Within Thailand there are related established educational curricula but less is known about how graduate practitioners enact ideas in practice and how these can influence policy at local levels. The aim of this inquiry was to develop family nursing practice in primary care settings in the Isaan region or Northeastern Thailand and to distill what worked well into a nursing model to guide practice. An appreciative inquiry approach involving analysis of written reports, focus group discussions and individual interviews was used to synthesize what worked well for fourteen family nurses involved in primary care delivery and to build the related model. Three main strategies were seen to offer a basis for optimal care delivery, namely: enacting a participatory action approach mobilizing families' social capital; using family nursing process; and implementing action strategies within communities. These were distilled into a new conceptual model. The model has some features in common with related community partnership models and the World Health Organization Europe Family Health Nurse model, but highlights practical strategies for family nursing enactment. The model offers a basis not only for planning and implementing family care to help prevent cancer and other diseases but also for education of nurses and health care providers working in communities. This articulation of what works in this culture also offers possible transference to different contexts internationally, with related potential to inform health and social care policies, and international development of care models.

The swine flu vaccine, public attitudes, and researcher interpretations: a systematic review of qualitative research.

PubMed

Carlsen, Benedicte; Glenton, Claire

2016-06-24

During pandemics, health authorities may be uncertain about the spread and severity of the disease and the effectiveness and safety of available interventions. This was the case during the swine flu (H1N1) pandemic of 2009-2010, and governments were forced to make decisions despite these uncertainties. While many countries chose to implement wide scale vaccination programmes, few accomplished their vaccination goals. Many research studies aiming to explore barriers and facilitators to vaccine uptake have been conducted in the aftermath of the pandemic, including several qualitative studies. 1. To explore public attitudes to the swine flu vaccine in different countries through a review of qualitative primary studies. 2. To describe and discuss the implications drawn by the primary study authors. Systematic review of qualitative research studies, using a broadly comparative cross case-study approach. Study quality was appraised using an adaptation of the Critical Appraisal Skills Programme (CASP) quality assessment tool. The review indicates that the public had varying opinions about disease risk and prevalence and had concerns about vaccine safety. Most primary study authors concluded that participants were uninformed, and that more information about the disease and the vaccine would have led to an increase in vaccine uptake. We find these conclusions problematic. We suggest instead that people's questions and concerns were legitimate given the uncertainties of the situation at the time and the fact that the authorities did not have the necessary information to convince the public. Our quality assessment of the included studies points to a lack of reflexivity and a lack of information about study context. We suggest that these study weaknesses are tied to primary study authors' lack of acknowledgement of the uncertainties surrounding the disease and the vaccine. While primary study authors suggest that authorities could increase vaccine uptake through increased information, we suggest instead that health authorities should be more transparent in their information and decision-making processes in future pandemic situations.

The African Turquoise Killifish: A Model for Exploring Vertebrate Aging and Diseases in the Fast Lane.

PubMed

Harel, Itamar; Brunet, Anne

2015-01-01

Why and how organisms age remains a mystery, and it defines one of the biggest challenges in biology. Aging is also the primary risk factor for many human pathologies, such as cancer, diabetes, cardiovascular diseases, and neurodegenerative diseases. Thus, manipulating the aging rate and potentially postponing the onset of these devastating diseases could have a tremendous impact on human health. Recent studies, relying primarily on nonvertebrate short-lived model systems, have shown the importance of both genetic and environmental factors in modulating the aging rate. However, relatively little is known about aging in vertebrates or what processes may be unique and specific to these complex organisms. Here we discuss how advances in genomics and genome editing have significantly expanded our ability to probe the aging process in a vertebrate system. We highlight recent findings from a naturally short-lived vertebrate, the African turquoise killifish, which provides an attractive platform for exploring mechanisms underlying vertebrate aging and age-related diseases. Copyright © 2015 Cold Spring Harbor Laboratory Press; all rights reserved.

Alignment between Chronic Disease Policy and Practice: Case Study at a Primary Care Facility

PubMed Central

Draper, Claire A.; Draper, Catherine E.; Bresick, Graham F.

2014-01-01

Background Chronic disease is by far the leading cause of death worldwide and of increasing concern in low- and middle-income countries, including South Africa, where chronic diseases disproportionately affect the poor living in urban settings. The Provincial Government of the Western Cape (PGWC) has prioritized the management of chronic diseases and has developed a policy and framework (Adult Chronic Disease Management Policy 2009) to guide and improve the prevention and management of chronic diseases at a primary care level. The aim of this study is to assess the alignment of current primary care practices with the PGWC Adult Chronic Disease Management policy. Methods One comprehensive primary care facility in a Cape Town health district was used as a case study. Data was collected via semi-structured interviews (n = 10), focus groups (n = 8) and document review. Participants in this study included clinical staff involved in chronic disease management at the facility and at a provincial level. Data previously collected using the Integrated Audit Tool for Chronic Disease Management (part of the PGWC Adult Chronic Disease Management policy) formed the basis of the guide questions used in focus groups and interviews. Results The results of this research indicate a significant gap between policy and its implementation to improve and support chronic disease management at this primary care facility. A major factor seems to be poor policy knowledge by clinicians, which contributes to an individual rather than a team approach in the management of chronic disease patients. Poor interaction between facility- and community-based services also emerged. A number of factors were identified that seemed to contribute to poor policy implementation, the majority of which were staff related and ultimately resulted in a decrease in the quality of patient care. Conclusions Chronic disease policy implementation needs to be improved in order to support chronic disease management at this facility. It is possible that similar findings and factors are present at other primary care facilities in Cape Town. At a philosophical level, this research highlights the tension between primary health care principles and a diseased-based approach in a primary care setting. PMID:25141191

Alignment between chronic disease policy and practice: case study at a primary care facility.

PubMed

Draper, Claire A; Draper, Catherine E; Bresick, Graham F

2014-01-01

Chronic disease is by far the leading cause of death worldwide and of increasing concern in low- and middle-income countries, including South Africa, where chronic diseases disproportionately affect the poor living in urban settings. The Provincial Government of the Western Cape (PGWC) has prioritized the management of chronic diseases and has developed a policy and framework (Adult Chronic Disease Management Policy 2009) to guide and improve the prevention and management of chronic diseases at a primary care level. The aim of this study is to assess the alignment of current primary care practices with the PGWC Adult Chronic Disease Management policy. One comprehensive primary care facility in a Cape Town health district was used as a case study. Data was collected via semi-structured interviews (n = 10), focus groups (n = 8) and document review. Participants in this study included clinical staff involved in chronic disease management at the facility and at a provincial level. Data previously collected using the Integrated Audit Tool for Chronic Disease Management (part of the PGWC Adult Chronic Disease Management policy) formed the basis of the guide questions used in focus groups and interviews. The results of this research indicate a significant gap between policy and its implementation to improve and support chronic disease management at this primary care facility. A major factor seems to be poor policy knowledge by clinicians, which contributes to an individual rather than a team approach in the management of chronic disease patients. Poor interaction between facility- and community-based services also emerged. A number of factors were identified that seemed to contribute to poor policy implementation, the majority of which were staff related and ultimately resulted in a decrease in the quality of patient care. Chronic disease policy implementation needs to be improved in order to support chronic disease management at this facility. It is possible that similar findings and factors are present at other primary care facilities in Cape Town. At a philosophical level, this research highlights the tension between primary health care principles and a diseased-based approach in a primary care setting.

Parkinson’s disease managing reversible neurodegeneration

PubMed Central

Hinz, Marty; Stein, Alvin; Cole, Ted; McDougall, Beth; Westaway, Mark

2016-01-01

Traditionally, the Parkinson’s disease (PD) symptom course has been classified as an irreversible progressive neurodegenerative disease. This paper documents 29 PD and treatment-induced systemic depletion etiologies which cause and/or exacerbate the seven novel primary relative nutritional deficiencies associated with PD. These reversible relative nutritional deficiencies (RNDs) may facilitate and accelerate irreversible progressive neurodegeneration, while other reversible RNDs may induce previously undocumented reversible pseudo-neurodegeneration that is hiding in plain sight since the symptoms are identical to the symptoms being experienced by the PD patient. Documented herein is a novel nutritional approach for reversible processes management which may slow or halt irreversible progressive neurodegenerative disease and correct reversible RNDs whose symptoms are identical to the patient’s PD symptoms. PMID:27103805

Health Supervision in the Management of Children and Adolescents With IBD: NASPGHAN Recommendations

PubMed Central

Rufo, Paul A.; Denson, Lee A.; Sylvester, Francisco A.; Szigethy, Eva; Sathya, Pushpa; Lu, Ying; Wahbeh, Ghassan T.; Sena, Laureen M.; Faubion, William A.

2014-01-01

Ulcerative colitis (UC) and Crohn disease (CD), collectively referred to as inflammatory bowel disease (IBD), are chronic inflammatory disorders that can affect the gastrointestinal tract of children and adults. Like other autoimmune processes, the cause(s) of these disorders remain unknown but likely involves some interplay between genetic vulnerability and environmental factors. Children, in particular with UC or CD, can present to their primary care providers with similar symptoms, including abdominal pain, diarrhea, weight loss, and bloody stool. Although UC and CD are more predominant in adults, epidemiologic studies have demonstrated that a significant percentage of these patients were diagnosed during childhood. The chronic nature of the inflammatory process observed in these children and the waxing and waning nature of their clinical symptoms can be especially disruptive to their physical, social, and academic development. As such, physicians caring for children must consider these diseases when evaluating patients with compatible symptoms. Recent research efforts have made available a variety of more specific and effective pharmacologic agents and improved endoscopic and radiologic assessment tools to assist clinicians in the diagnosis and interval assessment of their patients with IBD; however, as the level of complexity of these interventions has increased, so too has the need for practitioners to become familiar with a wider array of treatments and the risks and benefits of particular diagnostic testing. Nonetheless, in most cases, and especially when frequent visits to subspecialty referral centers are not geographically feasible, primary care providers can be active participants in the management of their pediatric patients with IBD. The goal of this article is to educate and assist pediatricians and adult gastroenterology physicians caring for children with IBD, and in doing so, help to develop more collaborative care plans between primary care and subspecialty providers. PMID:22516861

Health supervision in the management of children and adolescents with IBD: NASPGHAN recommendations.

PubMed

Rufo, Paul A; Denson, Lee A; Sylvester, Francisco A; Szigethy, Eva; Sathya, Pushpa; Lu, Ying; Wahbeh, Ghassan T; Sena, Laureen M; Faubion, William A

2012-07-01

Ulcerative colitis (UC) and Crohn disease (CD), collectively referred to as inflammatory bowel disease (IBD), are chronic inflammatory disorders that can affect the gastrointestinal tract of children and adults. Like other autoimmune processes, the cause(s) of these disorders remain unknown but likely involves some interplay between genetic vulnerability and environmental factors. Children, in particular with UC or CD, can present to their primary care providers with similar symptoms, including abdominal pain, diarrhea, weight loss, and bloody stool. Although UC and CD are more predominant in adults, epidemiologic studies have demonstrated that a significant percentage of these patients were diagnosed during childhood. The chronic nature of the inflammatory process observed in these children and the waxing and waning nature of their clinical symptoms can be especially disruptive to their physical, social, and academic development. As such, physicians caring for children must consider these diseases when evaluating patients with compatible symptoms. Recent research efforts have made available a variety of more specific and effective pharmacologic agents and improved endoscopic and radiologic assessment tools to assist clinicians in the diagnosis and interval assessment of their patients with IBD; however, as the level of complexity of these interventions has increased, so too has the need for practitioners to become familiar with a wider array of treatments and the risks and benefits of particular diagnostic testing. Nonetheless, in most cases, and especially when frequent visits to subspecialty referral centers are not geographically feasible, primary care providers can be active participants in the management of their pediatric patients with IBD. The goal of this article is to educate and assist pediatricians and adult gastroenterology physicians caring for children with IBD, and in doing so, help to develop more collaborative care plans between primary care and subspecialty providers.

Testing the Role of p21-Activated Kinases in Schwannoma Formation Using a Novel Genetically Engineered Murine Model that Closely Phenocopies Human NF2 Disease

DTIC Science & Technology

2015-06-01

preclinical models of NF1? Can whole kinome analysis predict pathways for drug resistance in treated mice? Procuring Contracting/Grants Officer: Emily...cells. b) Evaluate transduction of hydroxyethyl starch (HES)-processed hematopoietic cells. c) Monitor gene transfer in primary FANCC-/- progenitors

[Descending ocular myopathy].

PubMed

de Freitas, M R; Nascimento, O J

1975-06-01

The case of a 23 years old female patient, with primary involvement of the extraocular and faringeal muscles without familiar history is reported. Electromyographic and muscular biopsy studies proved the myogenic nature of the process. A clinical comparison between the ocular myopathy and the descending ocular myopathy is made, the authors thinking that both of them would be variants of the same muscle disease.

Exposing Cancer Cells' Secret Aides to Spread Disease to Distant Sites | Center for Cancer Research

Cancer.gov

Researchers are shedding new light on the way cancer spreads from the primary organ to distant sites in the body, a process called metastasis. The assault of metastatic tumors on vital organs too frequently results in death, and until recently, little was known about the molecular mechanisms governing this devastating phenomenon.

Correlation of proteome-wide changes with social immunity behaviors provides insight into resistance to the parasitic mite, Varroa destructor, in the honey bee (Apis mellifera)

PubMed Central

2012-01-01

Background Disease is a major factor driving the evolution of many organisms. In honey bees, selection for social behavioral responses is the primary adaptive process facilitating disease resistance. One such process, hygienic behavior, enables bees to resist multiple diseases, including the damaging parasitic mite Varroa destructor. The genetic elements and biochemical factors that drive the expression of these adaptations are currently unknown. Proteomics provides a tool to identify proteins that control behavioral processes, and these proteins can be used as biomarkers to aid identification of disease tolerant colonies. Results We sampled a large cohort of commercial queen lineages, recording overall mite infestation, hygiene, and the specific hygienic response to V. destructor. We performed proteome-wide correlation analyses in larval integument and adult antennae, identifying several proteins highly predictive of behavior and reduced hive infestation. In the larva, response to wounding was identified as a key adaptive process leading to reduced infestation, and chitin biosynthesis and immune responses appear to represent important disease resistant adaptations. The speed of hygienic behavior may be underpinned by changes in the antenna proteome, and chemosensory and neurological processes could also provide specificity for detection of V. destructor in antennae. Conclusions Our results provide, for the first time, some insight into how complex behavioural adaptations manifest in the proteome of honey bees. The most important biochemical correlations provide clues as to the underlying molecular mechanisms of social and innate immunity of honey bees. Such changes are indicative of potential divergence in processes controlling the hive-worker maturation. PMID:23021491

Correlation of proteome-wide changes with social immunity behaviors provides insight into resistance to the parasitic mite, Varroa destructor, in the honey bee (Apis mellifera).

PubMed

Parker, Robert; Guarna, M Marta; Melathopoulos, Andony P; Moon, Kyung-Mee; White, Rick; Huxter, Elizabeth; Pernal, Stephen F; Foster, Leonard J

2012-06-29

Disease is a major factor driving the evolution of many organisms. In honey bees, selection for social behavioral responses is the primary adaptive process facilitating disease resistance. One such process, hygienic behavior, enables bees to resist multiple diseases, including the damaging parasitic mite Varroa destructor. The genetic elements and biochemical factors that drive the expression of these adaptations are currently unknown. Proteomics provides a tool to identify proteins that control behavioral processes, and these proteins can be used as biomarkers to aid identification of disease tolerant colonies. We sampled a large cohort of commercial queen lineages, recording overall mite infestation, hygiene, and the specific hygienic response to V. destructor. We performed proteome-wide correlation analyses in larval integument and adult antennae, identifying several proteins highly predictive of behavior and reduced hive infestation. In the larva, response to wounding was identified as a key adaptive process leading to reduced infestation, and chitin biosynthesis and immune responses appear to represent important disease resistant adaptations. The speed of hygienic behavior may be underpinned by changes in the antenna proteome, and chemosensory and neurological processes could also provide specificity for detection of V. destructor in antennae. Our results provide, for the first time, some insight into how complex behavioural adaptations manifest in the proteome of honey bees. The most important biochemical correlations provide clues as to the underlying molecular mechanisms of social and innate immunity of honey bees. Such changes are indicative of potential divergence in processes controlling the hive-worker maturation.

Neurological diseases and pain

PubMed Central

2012-01-01

Chronic pain is a frequent component of many neurological disorders, affecting 20–40% of patients for many primary neurological diseases. These diseases result from a wide range of pathophysiologies including traumatic injury to the central nervous system, neurodegeneration and neuroinflammation, and exploring the aetiology of pain in these disorders is an opportunity to achieve new insight into pain processing. Whether pain originates in the central or peripheral nervous system, it frequently becomes centralized through maladaptive responses within the central nervous system that can profoundly alter brain systems and thereby behaviour (e.g. depression). Chronic pain should thus be considered a brain disease in which alterations in neural networks affect multiple aspects of brain function, structure and chemistry. The study and treatment of this disease is greatly complicated by the lack of objective measures for either the symptoms or the underlying mechanisms of chronic pain. In pain associated with neurological disease, it is sometimes difficult to obtain even a subjective evaluation of pain, as is the case for patients in a vegetative state or end-stage Alzheimer's disease. It is critical that neurologists become more involved in chronic pain treatment and research (already significant in the fields of migraine and peripheral neuropathies). To achieve this goal, greater efforts are needed to enhance training for neurologists in pain treatment and promote greater interest in the field. This review describes examples of pain in different neurological diseases including primary neurological pain conditions, discusses the therapeutic potential of brain-targeted therapies and highlights the need for objective measures of pain. PMID:22067541

The Ying and Yang of STAT3 in Human Disease.

PubMed

Vogel, Tiphanie P; Milner, Joshua D; Cooper, Megan A

2015-10-01

The transcription factor signal transducer and activator of transcription 3 (STAT3) is a critical regulator of multiple, diverse cellular processes. Heterozgyous, germline, loss-of-function mutations in STAT3 lead to the primary immune deficiency Hyper-IgE syndrome. Heterozygous, somatic, gain-of-function mutations in STAT3 have been reported in malignancy. Recently, germline, heterozygous mutations in STAT3 that confer a gain-of-function have been discovered and result in early-onset, multi-organ autoimmunity. This review summarizes what is known about the role of STAT3 in human disease.

Conditional deletion of p53 and Rb in the renin-expressing compartment of the pancreas leads to a highly penetrant metastatic pancreatic neuroendocrine carcinoma

PubMed Central

Glenn, Sean T.; Jones, Craig A.; Sexton, Sandra; LeVea, Charles M.; Caraker, Susan M.; Hajduczok, George; Gross, Kenneth W.

2014-01-01

Efforts to model human pancreatic neuroendocrine tumors (PanNET) in animals have been moderately successful, with minimal evidence for glucagonomas or metastatic spread. The renin gene while classically associated with expression in the kidney is also expressed in many other extra-renal tissues including the pancreas. To induce tumorigenesis within renin specific tissues, floxed alleles of p53 and Rb were selectively abrogated using Cre-recombinase driven by the renin promoter. The primary neoplasm generated is a highly metastatic islet cell carcinoma of the pancreas. Lineage tracing identifies descendants of renin-expressing cells as pancreatic alpha cells despite a lack of active renin expression in the mature pancreas. Both primary and metastatic tumors express high levels of glucagon, furthermore an increased level of glucagon is found in the serum identifying the pancreatic cancer as a functional glucagonoma. This new model is highly penetrant and exhibits robust frequency of metastases to lymph nodes and liver, mimicking human disease and provides a useful platform for better understanding pancreatic endocrine differentiation and development, as well as islet cell carcinogenesis. The use of fluorescent reporters for lineage tracing of the cells contributing to disease initiation and progression provides a unique opportunity to dissect the timeline of disease, examining mechanisms of the metastatic process, as well as recovering primary and metastatic cells for identifying co-operating mutations that are necessary for progression of disease. PMID:24292676

Conditional deletion of p53 and Rb in the renin-expressing compartment of the pancreas leads to a highly penetrant metastatic pancreatic neuroendocrine carcinoma.

PubMed

Glenn, S T; Jones, C A; Sexton, S; LeVea, C M; Caraker, S M; Hajduczok, G; Gross, K W

2014-12-11

Efforts to model human pancreatic neuroendocrine tumors (PanNETs) in animals have been moderately successful, with minimal evidence for glucagonomas or metastatic spread. The renin gene, although classically associated with expression in the kidney, is also expressed in many other extrarenal tissues including the pancreas. To induce tumorigenesis within rennin-specific tissues, floxed alleles of p53 and Rb were selectively abrogated using Cre-recombinase driven by the renin promoter. The primary neoplasm generated is a highly metastatic islet cell carcinoma of the pancreas. Lineage tracing identifies descendants of renin-expressing cells as pancreatic alpha cells despite a lack of active renin expression in the mature pancreas. Both primary and metastatic tumors express high levels of glucagon; furthermore, an increased level of glucagon is found in the serum, identifying the pancreatic cancer as a functional glucagonoma. This new model is highly penetrant and exhibits robust frequency of metastases to the lymph nodes and the liver, mimicking human disease, and provides a useful platform for better understanding pancreatic endocrine differentiation and development, as well as islet cell carcinogenesis. The use of fluorescent reporters for lineage tracing of the cells contributing to disease initiation and progression provides an unique opportunity to dissect the timeline of disease, examining mechanisms of the metastatic process, as well as recovering primary and metastatic cells for identifying cooperating mutations that are necessary for progression of disease.

Implementing and evaluating a program to facilitate chronic disease prevention and screening in primary care: a mixed methods program evaluation.

PubMed

Manca, Donna Patricia; Aubrey-Bassler, Kris; Kandola, Kami; Aguilar, Carolina; Campbell-Scherer, Denise; Sopcak, Nicolette; O'Brien, Mary Ann; Meaney, Christopher; Faria, Vee; Baxter, Julia; Moineddin, Rahim; Salvalaggio, Ginetta; Green, Lee; Cave, Andrew; Grunfeld, Eva

2014-10-08

The objectives of this paper are to describe the planned implementation and evaluation of the Building on Existing Tools to Improve Chronic Disease Prevention and Screening in Primary Care (BETTER 2) program which originated from the BETTER trial. The pragmatic trial, informed by the Chronic Care Model, demonstrated the effectiveness of an approach to Chronic Disease Prevention and Screening (CDPS) involving the use of a new role, the prevention practitioner. The desired goals of the program are improved clinical outcomes, reduction in the burden of chronic disease, and improved sustainability of the health-care system through improved CDPS in primary care. The BETTER 2 program aims to expand the implementation of the intervention used in the original BETTER trial into communities across Canada (Alberta, Ontario, Newfoundland and Labrador, the Northwest Territories and Nova Scotia). This proactive approach provides at-risk patients with an intervention from the prevention practitioner, a health-care professional. Using the BETTER toolkit, the prevention practitioner determines which CDPS actions the patient is eligible to receive, and through shared decision-making and motivational interviewing, develops a unique and individualized 'prevention prescription' with the patient. This intervention is 1) personalized; 2) addressing multiple conditions; 3) integrated through linkages to local, regional, or national resources; and 4) longitudinal by assessing patients over time. The BETTER 2 program brings together primary care providers, policy/decision makers and researchers to work towards improving CDPS in primary care. The target patient population is adults aged 40-65. The reach, effectiveness, adoption, implementation, maintain (RE-AIM) framework will inform the evaluation of the program through qualitative and quantitative methods. A composite index will be used to quantitatively assess the effectiveness of the prevention practitioner intervention. The CDPS actions comprising the composite index include the following: process measures, referral/treatment measures, and target/change outcome measures related to cardiovascular disease, diabetes, cancer and associated lifestyle factors. The BETTER 2 program is a collaborative approach grounded in practice and built from existing work (i.e., integration not creation). The program evaluation is designed to provide an understanding of issues impacting the implementation of an effective approach for CDPS within primary care that may be adapted to become sustainable in the non-research setting.

Evaluation of a tailored implementation strategy to improve the management of patients with chronic obstructive pulmonary disease in primary care: a study protocol of a cluster randomized trial

PubMed Central

2014-01-01

Background Chronic obstructive pulmonary disease (COPD) remains a major health problem, strongly related to smoking. Despite the publication of practice guidelines on prevention and treatment, not all patients with the disease receive the recommended healthcare, particularly with regard to smoking cessation advice where applicable. We have developed a tailored implementation strategy for enhancing general practitioners’ adherence to the disease management guidelines. The primary aim of the study is to evaluate the effects of this tailored implementation intervention on general practitioners’ adherence to guidelines. Methods/Design A pragmatic two-arm cluster randomized trial has been planned to compare care following the implementation of tailored interventions of four recommendations in COPD patients against usual care. The study will involve 18 general practices (9 in the intervention group and 9 in the control group) in Poland, each with at least 80 identified (at the baseline) patients with diagnosed COPD. The nine control practices will provide usual care without any interventions. Tailored interventions to implement four recommendations will be delivered in the remaining nine practices. At follow-up after nine months, data will be collected for all 18 general practices. The primary outcome measure is physicians’ adherence to all four recommendations: brief anti-smoking advice, dyspnea assessment, care checklist utilization and demonstration to patients of correct inhaler use. This measurement will be based on data extracted from identified patients’ records. Additionally, we will survey and interview patients with chronic obstructive pulmonary disease about the process of care. Discussion The results of this trial will be directly applicable to primary care in Poland and add to the growing body of evidence on interventions to improve chronic illness care. Trial registration This trial has been registered with Clinical Trials Protocol Registration System. Trial number: NCT01893476. PMID:24708623

Simplified lipid guidelines: Prevention and management of cardiovascular disease in primary care.

PubMed

Allan, G Michael; Lindblad, Adrienne J; Comeau, Ann; Coppola, John; Hudson, Brianne; Mannarino, Marco; McMinis, Cindy; Padwal, Raj; Schelstraete, Christine; Zarnke, Kelly; Garrison, Scott; Cotton, Candra; Korownyk, Christina; McCormack, James; Nickel, Sharon; Kolber, Michael R

2015-10-01

To develop clinical practice guidelines for a simplified approach to primary prevention of cardiovascular disease (CVD), concentrating on CVD risk estimation and lipid management for primary care clinicians and their teams; we sought increased contribution from primary care professionals with little or no conflict of interest and focused on the highest level of evidence available. Nine health professionals (4 family physicians, 2 internal medicine specialists, 1 nurse practitioner, 1 registered nurse, and 1 pharmacist) and 1 nonvoting member (pharmacist project manager) comprised the overarching Lipid Pathway Committee (LPC). Member selection was based on profession, practice setting, and location, and members disclosed any actual or potential conflicts of interest. The guideline process was iterative through online posting, detailed evidence review, and telephone and online meetings. The LPC identified 12 priority questions to be addressed. The Evidence Review Group answered these questions. After review of the answers, key recommendations were derived through consensus of the LPC. The guidelines were drafted, refined, and distributed to a group of clinicians (family physicians, other specialists, pharmacists, nurses, and nurse practitioners) and patients for feedback, then refined again and finalized by the LPC. Recommendations are provided on screening and testing, risk assessments, interventions, follow-up, and the role of acetylsalicylic acid in primary prevention. These simplified lipid guidelines provide practical recommendations for prevention and treatment of CVD for primary care practitioners. All recommendations are intended to assist with, not dictate, decision making in conjunction with patients. Copyright© the College of Family Physicians of Canada.

Identification and treatment of older persons with sarcopenia.

PubMed

Lauretani, Fulvio; Bautmans, Ivan; De Vita, Francesca; Nardelli, Anna; Ceda, Gian Paolo; Maggio, Marcello

2014-12-01

In the last decades, sarcopenia in older persons has been operationalized by the assessment of lean body mass, muscle strength and/or physical performance. Several definitions of sarcopenia, using different parameters and cut-offs, have been proposed. However, which is the best definition to describe and to assess this condition is still matter of debate. Hand grip strength has been suggested as better predictor of incident mobility impairment and mortality, than skeletal muscle mass. In the light of the current knowledge, we sought to propose an operative approach for identifying and treating sarcopenic older persons according to main categories of sarcopenia: the age-related or primary sarcopenia and disease-related or secondary sarcopenia. We suggest that a quantitative assessment of grip strength alone might be sufficient to identify patients with primary sarcopenia. When chronic diseases accompany the ageing process, the combined assessment of muscle strength plus a balance test could be more appropriate. The identification of tests and pathological relevant cut-offs that facilitates the entry of sarcopenia into the clinical practice, could step forward researchers and physicians. This could be important for planning multidisciplinary models to maximize the maintenance of locomotive abilities especially in older persons affected by chronic diseases such as Parkinson's disease.

Recommendations for the development of rare disease drugs using the accelerated approval pathway and for qualifying biomarkers as primary endpoints.

PubMed

Kakkis, Emil D; O'Donovan, Mary; Cox, Gerald; Hayes, Mark; Goodsaid, Federico; Tandon, P K; Furlong, Pat; Boynton, Susan; Bozic, Mladen; Orfali, May; Thornton, Mark

2015-02-10

For rare serious and life-threatening disorders, there is a tremendous challenge of transforming scientific discoveries into new drug treatments. This challenge has been recognized by all stakeholders who endorse the need for flexibility in the regulatory review process for novel therapeutics to treat rare diseases. In the United States, the best expression of this flexibility was the creation of the Accelerated Approval (AA) pathway. The AA pathway is critically important for the development of treatments for diseases with high unmet medical need and has been used extensively for drugs used to treat cancer and infectious diseases like HIV.In 2012, the AA provisions were amended to enhance the application of the AA pathway to expedite the development of drugs for rare disorders under the Food and Drug Administration Safety and Innovation Act (FDASIA). FDASIA, among many provisions, requires the development of a more relevant FDA guidance on the types of evidence that may be acceptable in support of using a novel surrogate endpoint. The application of AA to rare diseases requires more predictability to drive greater access to appropriate use of AA for more rare disease treatments that might not be developed otherwise.This white paper proposes a scientific framework for assessing biomarker endpoints to enhance the development of novel therapeutics for rare and devastating diseases currently without adequate treatment and is based on the opinions of experts in drug development and rare disease patient groups. Specific recommendations include: 1) Establishing regulatory rationale for increased AA access in rare disease programs; 2) Implementing a Biomarker Qualification Request Process to provide the opportunity for an early determination of biomarker acceptance; and 3) A proposed scientific framework for qualifying biomarkers as primary endpoints. The paper's final section highlights case studies of successful examples that have incorporated biomarker endpoints into FDA approvals for rare disease therapies. The focus of this paper is on the situation in the Unites States, but the recommendations are reasonably applicable to any jurisdiction.

Primary cilia proteins: ciliary and extraciliary sites and functions.

PubMed

Hua, Kiet; Ferland, Russell J

2018-05-01

Primary cilia are immotile organelles known for their roles in development and cell signaling. Defects in primary cilia result in a range of disorders named ciliopathies. Because this organelle can be found singularly on almost all cell types, its importance extends to most organ systems. As such, elucidating the importance of the primary cilium has attracted researchers from all biological disciplines. As the primary cilia field expands, caution is warranted in attributing biological defects solely to the function of this organelle, since many of these "ciliary" proteins are found at other sites in cells and likely have non-ciliary functions. Indeed, many, if not all, cilia proteins have locations and functions outside the primary cilium. Extraciliary functions are known to include cell cycle regulation, cytoskeletal regulation, and trafficking. Cilia proteins have been observed in the nucleus, at the Golgi apparatus, and even in immune synapses of T cells (interestingly, a non-ciliated cell). Given the abundance of extraciliary sites and functions, it can be difficult to definitively attribute an observed phenotype solely to defective cilia rather than to some defective extraciliary function or a combination of both. Thus, extraciliary sites and functions of cilia proteins need to be considered, as well as experimentally determined. Through such consideration, we will understand the true role of the primary cilium in disease as compared to other cellular processes' influences in mediating disease (or through a combination of both). Here, we review a compilation of known extraciliary sites and functions of "cilia" proteins as a means to demonstrate the potential non-ciliary roles for these proteins.

Practical Diagnosis and Management of Dementia Due to Alzheimer’s Disease in the Primary Care Setting: An Evidence-Based Approach

PubMed Central

Kerwin, Diana R.

2013-01-01

Objective: To review evidence-based guidance on the primary care of Alzheimer’s disease and clinical research on models of primary care for Alzheimer’s disease to present a practical summary for the primary care physician regarding the assessment and management of the disease. Data Sources: References were obtained via search using keywords Alzheimer’s disease AND primary care OR collaborative care OR case finding OR caregivers OR guidelines. Articles were limited to English language from January 1, 1990, to January 1, 2013. Study Selection: Articles were reviewed and selected on the basis of study quality and pertinence to this topic, covering a broad range of data and opinion across geographical regions and systems of care. The most recent published guidelines from major organizations were included. Results: Practice guidelines contained numerous points of consensus, with most advocating a central role for the primary care physician in the detection, diagnosis, and treatment of Alzheimer’s disease. Review of the literature indicated that optimal medical and psychosocial care for people with Alzheimer’s disease and their caregivers may be best facilitated through collaborative models of care involving the primary care physician working within a wider interdisciplinary team. Conclusions: Evidence-based guidelines assign the primary care physician a critical role in the care of people with Alzheimer’s disease. Research on models of care suggests the need for an appropriate medical/nonmedical support network to fulfill this role. Given the diversity and breadth of services required and the necessity for close coordination, nationwide implementation of team-based, collaborative care programs may represent the best option for improving care standards for patients with Alzheimer’s disease. PMID:24392252

Social deprivation and prevalence of chronic kidney disease in the UK: workload implications for primary care.

PubMed

Hossain, M P; Palmer, D; Goyder, E; El Nahas, A M

2012-02-01

The 'inverse care law' suggests that populations with the poorest health outcomes also tend to have poorer access to high-quality care. The new general practitioner (GP) contract in the UK aimed to reduce variations in care between areas by collecting information on processes and outcomes of chronic disease management. This study investigated whether, despite reductions in inequalities, primary care in deprived areas is still at a disadvantage due to the higher prevalence of chronic diseases, using chronic kidney disease (CKD) as an example. Initially, data from a hospital-based cohort of CKD patients were analysed to investigate the clustering of CKD patients across area-level deprivation using a geographical information system that employed kernel density estimation. Data from the Quality and Outcomes Framework were then analysed to explore the burden of CKD and associated non-communicable chronic diseases (NCD) and assess the potential impact on GPs' workload by area-level deprivation. There was a significant clustering of CKD patients referred to the hospital in the most deprived areas. Both the prevalence of CKD and associated conditions and caseload per GP were significantly higher in deprived areas. In the most deprived areas, there is an increased burden of major chronic disease and a higher caseload for clinicians. These reflect significant differences in workload for practices in deprived areas, which needs to be addressed.

Selection of Treatment Strategies among Patients with Type 2 Diabetes Mellitus in Malaysia: A Grounded Theory Approach

PubMed Central

Low, Lee Lan; Tong, Seng Fah; Low, Wah Yun

2016-01-01

Background Diabetes Mellitus is a multifaceted chronic illness and its life-long treatment process requires patients to continuously engage with the healthcare system. The understanding of how patients manoeuvre through the healthcare system for treatment is crucial in assisting them to optimise their disease management. This study aims to explore issues determining patients’ treatment strategies and the process of patients manoeuvring through the current healthcare system in selecting their choice of treatment for T2DM. Methods The Grounded Theory methodology was used. Twelve patients with Type 2 Diabetes Mellitus, nine family members and five healthcare providers from the primary care clinics were interviewed using a semi-structured interview guide. Three focus group discussions were conducted among thirteen healthcare providers from public primary care clinics. Both purposive and theoretical samplings were used for data collection. The interviews were audio-taped and transcribed verbatim, followed by line-by-line coding and constant comparison to identify the categories and core category. Results The concept of “experimentation” was observed in patients’ help-seeking behaviour. The “experimentation” process required triggers, followed by information seeking related to treatment characteristics from trusted family members, friends and healthcare providers to enable decisions to be made on the choice of treatment modalities. The whole process was dynamic and iterative through interaction with the healthcare system. The decision-making process in choosing the types of treatment was complex with an element of trial-and-error. The anchor of this process was the desire to fulfil the patient’s expected outcome. Conclusion Patients with Type 2 Diabetes Mellitus continuously used “experimentation” in their treatment strategies and help-seeking process. The “experimentation” process was experiential, with continuous evaluation, information seeking and decision-making tinged with the element of trial-and-error. The theoretical model generated from this study is abstract, is believed to have a broad applicability to other diseases, may be applied at varying stages of disease development and is non-context specific. PMID:26812053

Improving access to medicines for non-communicable diseases in rural India: a mixed methods study protocol using quasi-experimental design.

PubMed

Prashanth, N S; Elias, Maya Annie; Pati, Manoj Kumar; Aivalli, Praveenkumar; Munegowda, C M; Bhanuprakash, Srinath; Sadhana, S M; Criel, Bart; Bigdeli, Maryam; Devadasan, Narayanan

2016-08-22

India has the distinction of financing its healthcare mainly through out-of-pocket expenses by individual families contributing to catastrophic health expenditure and impoverishment. Nearly 70 % of the expenditure is on medicines purchased at private pharmacies. Patients with chronic ailments are especially affected, as they often need lifelong medicines. Over the past years in India, there have been several efforts to improve drug availability at government primary health centres. In this study, we aim to understand health system factors that affect utilisation and access to generic medicines for people with non-communicable diseases. This study aims to understand if (and how) a package of interventions targeting primary health centres and community participation platforms affect utilisation and access to generic medicines for people with non-communicable diseases in the current district context in India. This study will employ a quasi-experimental design and a qualitative theory-driven approach. PHCs will be randomly assigned to one of three arms of the intervention. In one arm, PHCs will receive inputs to optimise service delivery for non-communicable diseases, while the second arm will receive an additional package of interventions to strengthen community participation platforms for improving non-communicable disease care. The third arm will be the control. We will conduct household and facility surveys, before and after the intervention and will estimate the effect of the intervention by difference-in-difference analysis. Sample size for measuring effects was calculated based on obtaining at least 30 households for each primary health centre spread across three distance-based clusters. Primary outcomes include availability and utilisation of medicines at primary health centres and out-of-pocket expenditure for medicines by non-communicable disease households. Focus group discussions with patients and in-depth interviews with health workers will also be conducted. Qualitative and process documentation data will be used to explain how the intervention could have worked. By taking into consideration several health system building blocks and trying to understand how they interact, our study aims to generate evidence for health planners on how to optimise health services to improve access to medicines. Protocol registered on Clinical Trials Registry of India with registration identifier number CTRI/2015/03/005640 on 17(th) March 2015.

Naegleria fowleri: Diagnosis, Pathophysiology of Brain Inflammation, and Antimicrobial Treatments.

PubMed

Pugh, J Jeffrey; Levy, Rebecca A

2016-09-21

Primary amoebic meningoencephalitis (PAM) is a very rare disease with a high mortality rate. PAM is caused by Naegleria fowleri, an amoeba which resides in freshwater lakes and ponds and can survive in inadequately chlorinated pools ( Lopez, C.; Budge, P.; Chen, J., et al. Primary amebic meningoencephalitis: a case report and literature review . Pediatr. Emerg. Care 2012 , 28 , 272 - 276 ). In the past 50 years, there have been over 130 cases of Naegleria induced PAM in the United States with only three known survivors; one survivor was diagnosed and treated at Arkansas Children's Hospital. Successful treatment of PAM started with a rapid diagnosis, extensive antimicrobial therapy including an investigational medication miltefosine, supportive care, an intraventricular shunt, and hypothermia. These treatments address different aspects of the disease process. Increased understanding of the diagnosis and treatment of PAM is important especially for patients who present with meningitis-like findings during the summer months.

Proposal for an integrated evaluation model for the study of whole systems health care in cancer.

PubMed

Jonas, Wayne B; Beckner, William; Coulter, Ian

2006-12-01

For more than 200 years, biomedicine has approached the treatment of disease by studying disease processes (patho-genesis), inferring causal connections and developing specific approaches for therapeutically interfering with those processes. This pathogenic approach has been highly successful in acute and traumatic disease but less successful in chronic disease, primarily because of the complex, multi-factorial nature of most chronic disease, which does not allow for simple causal inference or for simple therapeutic interventions. This article suggests that chronic disease is best approached by enhancing healing processes (salutogenesis) as a whole system. Because of the nature of complex systems in chronic disease, an evaluation model based on integrative medicine is felt to be more appropriate than a disease model. The authors propose and describe an integrated model for the evaluation of healing (IMEH) that collects multilevel "thick case" observational data in assessing complex practices for chronic disease. If successful, this approach could become a blueprint for studying healing capacity in whole medical systems, including complementary medicine, traditional medicine, and conventional primary care. In addition, streamlining data collection and applying rapid informatics management might allow for such data to be used in guiding clinical practice. The IMEH involves collection, integration, and potentially feedback of relevant variables in the following areas: (1) sociocultural, (2) psychological and behavioral, (3) clinical (diagnosis based), and (4) biological. Evaluation and integration of these components would involve specialized research teams that feed their data into a single data management and information analysis center. These data can then be subjected to descriptive and pathway analysis providing "bench and bedside" information.

[Interdisciplinary AWMF guideline for the diagnostics of primary immunodeficiency].

PubMed

Farmand, S; Baumann, U; von Bernuth, H; Borte, M; Foerster-Waldl, E; Franke, K; Habermehl, P; Kapaun, P; Klock, G; Liese, J; Marks, R; Müller, R; Nebe, T; Niehues, T; Schuster, V; Warnatz, K; Witte, T; Ehl, S; Schulze, I

2011-11-01

Primary immunodeficiencies are potentially life-threatening diseases. Over the last years, the clinical phenotype and the molecular basis of an increasing number of immunological defects have been characterized. However, in daily practice primary immunodeficiencies are still often diagnosed too late. Considering that an early diagnosis may reduce morbidity and mortality of affected patients, an interdisciplinary guideline for the diagnosis of primary immunodeficiencies was developed on behalf of the Arbeitsgemeinschaft Pädiatrische Immunologie (API) and the Deutsche Gesellschaft für Immunologie (DGfI). The guideline is based on expert opinion and on knowledge from other guidelines and recommendations from Germany and other countries, supplemented by data from studies that support the postulated key messages (level of evidence III). With the contribution of 20 representatives, belonging to 14 different medical societies and associations, a consensus-based guideline with a representative group of developers and a structured consensus process was created (S2k). Under the moderation of a representative of the Association of the Scientific Medical Societies in Germany (AWMF) the nominal group process took place in April 2011. The postulated key messages were discussed and voted on following a structured consensus procedure. In particular, modified warning signs for primary immunodeficiencies were formulated and immunological emergency situations were defined. © Georg Thieme Verlag KG Stuttgart · New York.

Quality indicators for the detection and management of chronic kidney disease in primary care in Canada derived from a modified Delphi panel approach.

PubMed

Tu, Karen; Bevan, Lindsay; Hunter, Katie; Rogers, Jess; Young, Jacqueline; Nesrallah, Gihad

2017-01-01

The detection and management of chronic kidney disease lies within primary care; however, performance measures applicable in the Canadian context are lacking. We sought to develop a set of primary care quality indicators for chronic kidney disease in the Canadian setting and to assess the current state of the disease's detection and management in primary care. We used a modified Delphi panel approach, involving 20 panel members from across Canada (10 family physicians, 7 nephrologists, 1 patient, 1 primary care nurse and 1 pharmacist). Indicators identified from peer-reviewed and grey literature sources were subjected to 3 rounds of voting to develop a set of quality indicators for the detection and management of chronic kidney disease in the primary care setting. The final indicators were applied to primary care electronic medical records in the Electronic Medical Record Administrative data Linked Database (EMRALD) to assess the current state of primary care detection and management of chronic kidney disease in Ontario. Seventeen indicators made up the final list, with 1 under the category Prevalence, Incidence and Mortality; 4 under Screening, Diagnosis and Risk Factors; 11 under Management; and 1 under Referral to a Specialist. In a sample of 139 993 adult patients not on dialysis, 6848 (4.9%) had stage 3 or higher chronic kidney disease, with the average age of patients being 76.1 years (standard deviation [SD] 11.0); 62.9% of patients were female. Diagnosis and screening for chronic kidney disease were poorly performed. Only 27.1% of patients with stage 3 or higher disease had their diagnosis documented in their cumulative patient profile. Albumin-creatinine ratio testing was only performed for 16.3% of patients with a low estimated glomerular filtration rate (eGFR) and for 28.5% of patients with risk factors for chronic kidney disease. Family physicians performed relatively better with the management of chronic kidney disease, with 90.4% of patients with stage 3 or higher disease having an eGFR performed in the previous 18 months and 83.1% having a blood pressure recorded in the previous 9 months. We propose a set of measurable indicators to evaluate the quality of the management of chronic kidney disease in primary care. These indicators may be used to identify opportunities to improve current practice in Canada.

What Are the Targets of Inflammatory Bowel Disease Management.

PubMed

Lega, Sara; Dubinsky, Marla C

2018-04-25

With recent evidence suggesting that keeping the inflammatory process under tight control prevents long-term disability, the aim of treatments in inflammatory bowel disease (IBD) has shifted from symptom control toward the resolution of bowel inflammation. Mucosal healing is currently recognized as the principal treatment target to be used in a "treat to target" paradigm, whereas histologic healing and normalization of biomarkers are being evaluated as potential future targets. Although symptom relief is no longer a sufficient target, patient experience with the disease is of unquestionable importance and should be assessed in the form of patient-reported outcomes, to be used as a co-primary target with an objective measure of disease activity. IBD in is a heterogeneous disease; thus besides defining common treatment targets, every effort should be made to deliver a personalized treatment plan based on the risk factors for disease progression and individual drug metabolism to improve treatment success.

Abnormal hepatic biochemistries and clinical liver disease in patients with primary Sjögren's syndrome.

PubMed

Montaño-Loza, Aldo J; Crispín-Acuña, José Carlos; Remes-Troche, José María; Uribe, Misael

2007-01-01

Patients with primary Sjögren's syndrome may present liver involvement. Our goals were to establish the prevalence of abnormal hepatic biochemistries and clinical liver disease in patients with primary Sjögren's syndrome and correlate their presence with other clinical and laboratory features. Ninety-five patients with diagnosis of primary Sjögren's syndrome were studied. Data on gender, age, clinical features, liver biochemistries, tests of inflammation and autoimmunity, and concomitant diseases were collected. Forty-two patients (44%) had abnormal hepatic biochemistries, and of these 19 patients (20%) had clinical liver disease. Patients with abnormal hepatic biochemistries had higher frequency of autoimmune hypotiroidism, arthritis, vasculitis, Raynaud's phenomenon, higher sedimentation rate,and higher frequency of antinuclear and antimitochondrial antibodies than patients with normal liver biochemistries (P < 0.05 for each). Patients with clinical liver disease had higher frequency of arthritis, vasculitis, and higher frequency of antimitochondrial antibodies than patients without clinical liver disease (P < 0.05 for each). Twenty-one patients had diagnosis of a specific liver disease, such as hepatitis C virus infection (n = 11), autoimmune hepatitis (n = 2), primary biliary cirrhosis (n =5),nonalcoholic fatty liver disease (n = 2), and hepatitis B virus infection (n = 1). In half of patients with liver involvement a definitive cause could not be identified. Liver involvement is frequently found in patients with primary Sjögren's syndrome, and its presence is associated with clinical features of systemic disease, and markers of autoimmunity and inflammation. There may be a subgroup of patients with liver involvement secondary to primary Sjögren's syndrome.

A systematic review of primary care models for non-communicable disease interventions in Sub-Saharan Africa.

PubMed

Kane, Jennifer; Landes, Megan; Carroll, Christopher; Nolen, Amy; Sodhi, Sumeet

2017-03-23

Chronic diseases, primarily cardiovascular disease, respiratory disease, diabetes and cancer, are the leading cause of death and disability worldwide. In sub-Saharan Africa (SSA), where communicable disease prevalence still outweighs that of non-communicable disease (NCDs), rates of NCDs are rapidly rising and evidence for primary healthcare approaches for these emerging NCDs is needed. A systematic review and evidence synthesis of primary care approaches for chronic disease in SSA. Quantitative and qualitative primary research studies were included that focused on priority NCDs interventions. The method used was best-fit framework synthesis. Three conceptual models of care for NCDs in low- and middle-income countries were identified and used to develop an a priori framework for the synthesis. The literature search for relevant primary research studies generated 3759 unique citations of which 12 satisfied the inclusion criteria. Eleven studies were quantitative and one used mixed methods. Three higher-level themes of screening, prevention and management of disease were derived. This synthesis permitted the development of a new evidence-based conceptual model of care for priority NCDs in SSA. For this review there was a near-consensus that passive rather than active case-finding approaches are suitable in resource-poor settings. Modifying risk factors among existing patients through advice on diet and lifestyle was a common element of healthcare approaches. The priorities for disease management in primary care were identified as: availability of essential diagnostic tools and medications at local primary healthcare clinics and the use of standardized protocols for diagnosis, treatment, monitoring and referral to specialist care.

Loss of function of ATXN1 increases amyloid beta-protein levels by potentiating beta-secretase processing of beta-amyloid precursor protein.

PubMed

Zhang, Can; Browne, Andrew; Child, Daniel; Divito, Jason R; Stevenson, Jesse A; Tanzi, Rudolph E

2010-03-19

Alzheimer disease (AD) is a devastating neurodegenerative disease with complex and strong genetic inheritance. Four genes have been established to either cause familial early onset AD (APP, PSEN1, and PSEN2) or to increase susceptibility for late onset AD (APOE). To date approximately 80% of the late onset AD genetic variance remains elusive. Recently our genome-wide association screen identified four novel late onset AD candidate genes. Ataxin 1 (ATXN1) is one of these four AD candidate genes and has been indicated to be the disease gene for spinocerebellar ataxia type 1, which is also a neurodegenerative disease. Mounting evidence suggests that the excessive accumulation of Abeta, the proteolytic product of beta-amyloid precursor protein (APP), is the primary AD pathological event. In this study, we ask whether ATXN1 may lead to AD pathogenesis by affecting Abeta and APP processing utilizing RNA interference in a human neuronal cell model and mouse primary cortical neurons. We show that knock-down of ATXN1 significantly increases the levels of both Abeta40 and Abeta42. This effect could be rescued with concurrent overexpression of ATXN1. Moreover, overexpression of ATXN1 decreased Abeta levels. Regarding the underlying molecular mechanism, we show that the effect of ATXN1 expression on Abeta levels is modulated via beta-secretase cleavage of APP. Taken together, ATXN1 functions as a genetic risk modifier that contributes to AD pathogenesis through a loss-of-function mechanism by regulating beta-secretase cleavage of APP and Abeta levels.

Loss of Function of ATXN1 Increases Amyloid β-Protein Levels by Potentiating β-Secretase Processing of β-Amyloid Precursor Protein*

PubMed Central

Zhang, Can; Browne, Andrew; Child, Daniel; DiVito, Jason R.; Stevenson, Jesse A.; Tanzi, Rudolph E.

2010-01-01

Alzheimer disease (AD) is a devastating neurodegenerative disease with complex and strong genetic inheritance. Four genes have been established to either cause familial early onset AD (APP, PSEN1, and PSEN2) or to increase susceptibility for late onset AD (APOE). To date ∼80% of the late onset AD genetic variance remains elusive. Recently our genome-wide association screen identified four novel late onset AD candidate genes. Ataxin 1 (ATXN1) is one of these four AD candidate genes and has been indicated to be the disease gene for spinocerebellar ataxia type 1, which is also a neurodegenerative disease. Mounting evidence suggests that the excessive accumulation of Aβ, the proteolytic product of β-amyloid precursor protein (APP), is the primary AD pathological event. In this study, we ask whether ATXN1 may lead to AD pathogenesis by affecting Aβ and APP processing utilizing RNA interference in a human neuronal cell model and mouse primary cortical neurons. We show that knock-down of ATXN1 significantly increases the levels of both Aβ40 and Aβ42. This effect could be rescued with concurrent overexpression of ATXN1. Moreover, overexpression of ATXN1 decreased Aβ levels. Regarding the underlying molecular mechanism, we show that the effect of ATXN1 expression on Aβ levels is modulated via β-secretase cleavage of APP. Taken together, ATXN1 functions as a genetic risk modifier that contributes to AD pathogenesis through a loss-of-function mechanism by regulating β-secretase cleavage of APP and Aβ levels. PMID:20097758

Entrepreneurship in health education and health promotion: five cardinal rules.

PubMed

Eddy, James M; Stellefson, Michael L

2009-07-01

The nature of health education and health promotion (HE/HP) offers a fertile ground for entrepreneurial activity. As primary prevention of chronic diseases becomes a more central component of the health and/ or medical care continuum, entrepreneurial opportunities for health educators will continue to expand. The process used to design, implement, and evaluate health promotion and disease prevention has clear articulation with entrepreneurial, marketing management, and other business processes. Thus, entrepreneurs in HE/HP must be able to utilize business process to facilitate creative, new HE/HP business ideas. The purpose of this article is to weave theory and practical application into a primer on entrepreneurial applications in HE/HP. More specifically, the authors meld their prospective experiences and expertise to provide background thoughts on entrepreneurship in HE/HP and develop a framework for establishing an entrepreneurial venture in HE/HP. Five Cardinal Rules for Entrepreneurs in HE/HP are proposed.

[Comparative research into sensitivity and specificity of immune-enzyme analysis with chemiluminescence and colorimetric detection for detecting antigens and antibodies to avian influenza viruses and newcastle disease].

PubMed

Vitkova, O N; Kapustina, T P; Mikhailova, V V; Safonov, G A; Vlasova, N N; Belousova, R V

2015-01-01

The goal of this work was to demonstrate the results of the development of the enzyme-linked immunosorbent tests with chemiluminescence detection and colorimetric detection of specific viral antigens and antibodies for identifying the avian influenza and the Newcastle disease viruses: high sensitivity and specificity of the immuno- chemiluminescence assay, which are 10-50 times higher than those of the ELISA colorimetric method. The high effectiveness of the results and the automation of the process of laboratory testing (using a luminometer) allow these methods to be recommended for including in primary screening tests for these infectious diseases.

Integrating physiotherapists within primary health care teams: perspectives of family physicians and nurse practitioners.

PubMed

Dufour, Sinéad Patricia; Brown, Judith; Deborah Lucy, S

2014-09-01

The international literature suggests a number of benefits related to integrating physiotherapists into primary health care (PHC) teams. Considering the mandate of PHC teams in Canada, emphasizing healthy living and chronic disease management, a broad range of providers, inclusive of physiotherapists is required. However, physiotherapists are only sparsely integrated into these teams. This study explores the perspectives of "core" PHC team members, family physicians and nurse practitioners, regarding the integration of physiotherapists within Ontario (Canada) PHC teams. Twenty individual semi-structured in-depth interviews were conducted, transcribed verbatim, and then analyzed following an iterative process drawing from an interpretive phenomenological approach. Five key themes emerged which highlighted "how physiotherapists could and do contribute as team members within PHC teams particularly related to musculoskeletal health and chronic disease management". The perceived value of physiotherapists within Ontario, Canada PHC teams was a unanimous sentiment particularly in terms of musculoskeletal health, chronic disease management and maximizing health human resources efficiency to ensure the right care, is delivered by the right practitioner, at the right time.

Investigating the biochemical progression of liver disease through fibrosis, cirrhosis, dysplasia, and hepatocellular carcinoma using Fourier transform infrared spectroscopic imaging

NASA Astrophysics Data System (ADS)

Sreedhar, Hari; Pant, Mamta; Ronquillo, Nemencio R.; Davidson, Bennett; Nguyen, Peter; Chennuri, Rohini; Choi, Jacqueline; Herrera, Joaquin A.; Hinojosa, Ana C.; Jin, Ming; Kajdacsy-Balla, Andre; Guzman, Grace; Walsh, Michael J.

2014-03-01

Hepatocellular carcinoma (HCC) is the most common form of primary hepatic carcinoma. HCC ranks the fourth most prevalent malignant tumor and the third leading cause of cancer related death in the world. Hepatocellular carcinoma develops in the context of chronic liver disease and its evolution is characterized by progression through intermediate stages to advanced disease and possibly even death. The primary sequence of hepatocarcinogenesis includes the development of cirrhosis, followed by dysplasia, and hepatocellular carcinoma.1 We addressed the utility of Fourier Transform Infrared (FT-IR) spectroscopic imaging, both as a diagnostic tool of the different stages of the disease and to gain insight into the biochemical process associated with disease progression. Tissue microarrays were obtained from the University of Illinois at Chicago tissue bank consisting of liver explants from 12 transplant patients. Tissue core biopsies were obtained from each explant targeting regions of normal, liver cell dysplasia including large cell change and small cell change, and hepatocellular carcinoma. We obtained FT-IR images of these tissues using a modified FT-IR system with high definition capabilities. Firstly, a supervised spectral classifier was built to discriminate between normal and cancerous hepatocytes. Secondly, an expanded classifier was built to discriminate small cell and large cell changes in liver disease. With the emerging advances in FT-IR instrumentation and computation there is a strong drive to develop this technology as a powerful adjunct to current histopathology approaches to improve disease diagnosis and prognosis.

Primary Tumor Thickness is a Prognostic Factor in Stage IV Melanoma: A Retrospective Study of Primary Tumor Characteristics.

PubMed

Luen, Stephen; Wong, Siew Wei; Mar, Victoria; Kelly, John W; McLean, Catriona; McArthur, Grant A; Haydon, Andrew

2018-01-01

Stage IV melanoma exhibits a diverse range of tumor biology from indolent to aggressive disease. Many important prognostic factors have already been identified. Despite this, the behavior of metastatic melanoma remains difficult to predict. We sought to determine if any primary tumor characteristics affect survival following the diagnosis of stage IV melanoma. All patients diagnosed with stage IV melanoma between January 2003 and December 2012 were identified from the Victorian Melanoma Service database. Retrospective chart review was performed to collect data on primary tumor characteristics (thickness, ulceration, mitotic rate, melanoma subtype, or occult primary). Known and suspected prognostic factors were additionally collected (time to diagnosis of stage IV disease, age, sex, stage, receipt of chemotherapy, and era of recurrence). The effect of primary tumor characteristics on overall survival from the date of diagnosis of stage IV disease was assessed. A total of 227 patients with a median follow-up of 5 years from diagnosis of stage IV disease were identified. Median overall survival of the cohort was 250 days.Of the primary tumor characteristics assessed, only tumor thickness affected survival from diagnosis of stage IV disease, hazard ratio=1.09 (1.02 to 1.16), P=0.008. This remained significant in multivariate analysis, P=0.007. Other primary tumor characteristics did not significantly influence survival. Primary tumor thickness is a significant prognostic factor in stage IV melanoma. Our data suggest that the biology of the primary melanoma may persist to influence the behavior of metastatic disease.

Rheumatologist and Primary Care Management of Cardiovascular Disease Risk in Rheumatoid Arthritis: Patient and Provider Perspectives.

PubMed

Bartels, Christie M; Roberts, Tonya J; Hansen, Karen E; Jacobs, Elizabeth A; Gilmore, Andrea; Maxcy, Courtney; Bowers, Barbara J

2016-04-01

Despite increased cardiovascular disease (CVD) risk, rheumatoid arthritis (RA) patients often lack CVD preventive care. We examined CVD preventive care processes from RA patient and provider perspectives to develop a process map for identifying targets for future interventions to improve CVD preventive care. Thirty-one participants (15 patients, 7 rheumatologists, and 9 primary care physicians [PCPs]) participated in interviews that were coded using NVivo software and analyzed using grounded theory techniques. Patients and providers reported that receipt of preventive care depends upon identifying and acting on risk factors, although most noted that both processes rarely occurred. Engagement in these processes was influenced by various provider-, system-, visit-, and patient-related conditions, such as patient activation or patients' knowledge about their risk. While nearly half of patients and PCPs were unaware of RA-CVD risk, all rheumatologists were aware of risk. Rheumatologists reported not systematically identifying risk factors, or, if identified, they described communicating about CVD risk factors via clinic notes to PCPs instead of acting directly due to perceived role boundaries. PCPs suggested that scheduling PCP visits could improve CVD risk management, and all participants viewed comanagement positively. Findings from this study illustrate important gaps and opportunities to support identifying and acting on CVD risk factors in RA patients from the provider, system, visit, and patient levels. Future work should investigate professional role support through improved guidelines, patient activation, and system-based RA-CVD preventive care strategies. © 2016, American College of Rheumatology.

Improving cardiovascular outcomes among Aboriginal Australians: Lessons from research for primary care

PubMed Central

Thompson, Sandra C; Haynes, Emma; Woods, John A; Bessarab, Dawn C; Dimer, Lynette A; Wood, Marianne M; Sanfilippo, Frank M; Hamilton, Sandra J; Katzenellenbogen, Judith M

2016-01-01

Background: The Aboriginal people of Australia have much poorer health and social indicators and a substantial life expectancy gap compared to other Australians, with premature cardiovascular disease a major contributor to poorer health. This article draws on research undertaken to examine cardiovascular disparities and focuses on ways in which primary care practitioners can contribute to reducing cardiovascular disparities and improving Aboriginal health. Methods: The overall research utilised mixed methods and included data analysis, interviews and group processes which included Aboriginal people, service providers and policymakers. Workshop discussions to identify barriers and what works were recorded by notes and on whiteboards, then distilled and circulated to participants and other stakeholders to refine and validate information. Additional engagement occurred through circulation of draft material and further discussions. This report distils the lessons for primary care practitioners to improve outcomes through management that is attentive to the needs of Aboriginal people. Results: Aspects of primordial, primary and secondary prevention are identified, with practical strategies for intervention summarised. The premature onset and high incidence of Aboriginal cardiovascular disease make prevention imperative and require that primary care practitioners understand and work to address the social underpinnings of poor health. Doctors are well placed to reinforce the importance of healthy lifestyle at all visits to involve the family and to reduce barriers which impede early care seeking. Ensuring better information for Aboriginal patients and better integrated care for patients who frequently have complex needs and multi-morbidities will also improve care outcomes. Conclusion: Primary care practitioners have an important role in improving Aboriginal cardiovascular care outcomes. It is essential that they recognise the special needs of their Aboriginal patients and work at multiple levels both outside and inside the clinic for prevention and management of disease. A toolkit of proactive and holistic opportunities for interventions is proposed. PMID:27928502

Prevention of Alzheimer disease: The roles of nutrition and primary care.

PubMed

Bane, Tabitha J; Cole, Connie

2015-05-15

Risk factors for developing Alzheimer disease include hypercholesterolemia, hypertension, obesity, and diabetes. Due to lack of effective treatments for Alzheimer disease, nutrition and primary prevention becomes important.

Social and diagnostic inequality in health.

PubMed

Bringedal, Berit; Tufte, Per Arne

2012-11-01

Empirical studies of social inequalities in health commonly take the diagnosing of disease for granted. Social inequalities in health are seen as the result of social processes, yet the diagnosis itself is rarely considered to contribute to such inequality. We argue that the influence of sociocultural and cognitive bias in the diagnosing process follows a social pattern, such that certain diagnoses are disproportionally over- or underrepresented in different socioeconomic groups due to interpretive bias of underlying symptoms. Norwegian data on sick leave for diffuse musculoskeletal and diffuse psychiatric disease in 2006 were analysed to study the distribution of the two diagnoses in different status groups. Socioeconomic status was measured by years of education. Diagnoses and occupational codes were based on national registers; diagnoses in accordance with the International Classification of Primary Care second edition. We compared occupations in technical sectors to occupations in the health sector and the relative number of cases of sick leave controlled for years of education, gender, occupational sector, and diagnosis. Data were analysed by cross-tabulation, ratio of diffuse psychiatric/musculoskeletal diseases, and logistic regression. The ratio of diffuse psychiatric/musculoskeletal diseases increases with education and decreases if the employee works in a technical job. The results challenge the traditional explanation that job features alone can explain the distribution of disease and suggest that a part of the persistent social inequality in health can be caused by the diagnosing process. In order to reach a better understanding of the processes behind the social inequalities in health, the diagnosing process itself should also be studied.

Critical factors in case management: practical lessons from a cardiac case management program.

PubMed

Stafford, Randall S; Berra, Kathy

2007-08-01

Case management (CM) is an important strategy for chronic disease care. By utilizing non-physician providers for conditions requiring ongoing care and follow-up, CM can facilitate guideline-concordant care, patient empowerment, and improvement in quality of life. We identify a series of critical factors required for successful CM implementation. Heart to Heart is a clinical trial evaluating CM for coronary heart disease (CHD) risk reduction in a multiethnic, low-income population. Patients at elevated cardiac risk were randomized to CM plus primary care (212 patients) or to primary care alone (207). Over a mean follow-up of 17 months, patients received face-to-face nurse and dietitian visits. Mean contact time was 14 hours provided at an estimated cost of $1250 per patient for the 341 (81%) patients completing follow-up. Visits emphasized behavior change, risk-factor monitoring, self-management skills, and guideline-based pharmacotherapy. A statistically significant reduction in mean Framingham risk probability occurred in CM plus primary care relative to primary care alone (1.6% decrease in 10-year CHD risk, p = 0.007). Favorable changes were noted across individual risk factors. Our findings suggest that successful CM implementation relies on choosing appropriate case managers and investing in training, integrating CM into existing care systems, delineating the scope and appropriate levels of clinical decision making, using information systems, and monitoring outcomes and costs. While our population, setting, and intervention model are unique, these insights are broadly relevant. If implemented with attention to critical factors, CM has great potential to improve the process and outcomes of chronic disease care.

Acceptability of screening for early detection of liver disease in hazardous/harmful drinkers in primary care.

PubMed

Eyles, Caroline; Moore, Michael; Sheron, Nicholas; Roderick, Paul; O'Brien, Wendy; Leydon, Geraldine M

2013-08-01

It is estimated that one-quarter of adults in the UK drink at harmful/hazardous levels leading to increased mortality and alcohol liver disease (ALD). The Alcohol Liver Disease Detection Study (ALDDeS) aimed to test out in primary care the feasibility of alcohol misuse screening in adults, using the AUDIT questionnaire, and to assess screening harmful/hazardous alcohol users for ALD using newer non-invasive serum markers of fibrosis. To explore patients' experiences of taking part in ALDDeS and understanding of the delivery and process of screening for ALD using self-report questionnaires and feedback of liver fibrosis risk using levels of non-invasive serum markers. A nested qualitative study based in five primary care practices in the UK. From a sample of patients who were identified as drinking at harmful/hazardous levels, 30 participants were identified by maximum variation sampling for qualitative in-depth interviews. Using the principles of constant comparison the transcribed interviews were thematically analysed. Receiving a postal AUDIT questionnaire was viewed as acceptable by participants. For some completing the AUDIT increased awareness of their hazardous alcohol use and a positive blood test indicating liver fibrosis was a catalyst for behaviour change. For others, a negative blood test result provided a licence to continue drinking at hazardous levels. A limited understanding of safe drinking and of ALD was common. Educational and training needs of primary care professionals must be taken into account, so that patients with marker levels indicating low risk of fibrosis are correctly informed about the likely risks of continuing to drink at the same levels.

Takayasu's disease in a young black boy.

PubMed

Oguntona, S A

2010-12-01

Takayusu's disease is a rare disease affecting women predominantly during the child- bearing age. It is a primary vasculitis condition of large-vessels that responds well to steroid therapy. Immunosuppressives and vascular reconstruction may be needed as necessary. Reference was made to the case note of this young boy who was being co-managed by cardiology and vascular clinics. The diagnosis of Takayasu's disease was confirmed by the rheumatology unit and appropriate literature search was done. Takayusu's disease responds well to steroid therapy as exemplified by this patient. There was no relapse of the active inflammation after six months of steroid therapy. A high index of suspicion must be exercise in diagnosing Takayasu's disease. It could be difficult to have a clue early in the disease process because of non-specific presentations. Appropriate referral should however be made to Rheumatologist when the diagnosis is suspected. This will go a long way in delaying the morbidity that is associated with this rare disease.

Inhibition of Super-Enhancer Activity in Autoinflammatory Site-Derived T Cells Reduces Disease-Associated Gene Expression.

PubMed

Peeters, Janneke G C; Vervoort, Stephin J; Tan, Sander C; Mijnheer, Gerdien; de Roock, Sytze; Vastert, Sebastiaan J; Nieuwenhuis, Edward E S; van Wijk, Femke; Prakken, Berent J; Creyghton, Menno P; Coffer, Paul J; Mokry, Michal; van Loosdregt, Jorg

2015-09-29

The underlying molecular mechanisms for many autoimmune diseases are poorly understood. Juvenile idiopathic arthritis (JIA) is an exceptionally well-suited model for studying autoimmune diseases due to its early onset and the possibility to analyze cells derived from the site of inflammation. Epigenetic profiling, utilizing primary JIA patient-derived cells, can contribute to the understanding of autoimmune diseases. With H3K27ac chromatin immunoprecipitation, we identified a disease-specific, inflammation-associated, typical enhancer and super-enhancer signature in JIA patient synovial-fluid-derived CD4(+) memory/effector T cells. RNA sequencing of autoinflammatory site-derived patient T cells revealed that BET inhibition, utilizing JQ1, inhibited immune-related super-enhancers and preferentially reduced disease-associated gene expression, including cytokine-related processes. Altogether, these results demonstrate the potential use of enhancer profiling to identify disease mediators and provide evidence for BET inhibition as a possible therapeutic approach for the treatment of autoimmune diseases. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Introducing care pathway commissioning to primary dental care: measuring performance.

PubMed

Harris, R; Bridgman, C; Ahmad, M; Bowes, L; Haley, R; Saleem, S; Singh, R; Taylor, S

2011-12-09

Care pathways have been used in a variety of ways: firstly to support quality improvement through standardising clinical processes, but also for secondary purposes, by purchasers of healthcare, to monitor activity and health outcomes and to commission services. This paper focuses on reporting a secondary use of care pathways: to commission and monitor performance of primary dental care services. Findings of a project involving three dental practices implementing a system based on rating patients according to their risk of disease and need for care are outlined. Data from surgery-based clinical databases and interviews from commissioners and providers are reported. The use of both process and outcome key performance indicators in this context is discussed, as well as issues which arise such as attributability of outcome measures and strategic approaches to improving quality of care.

Natural Modulators of Amyloid-Beta Precursor Protein Processing

PubMed Central

Zhang, Can; Tanzi, Rudolph E.

2013-01-01

Alzheimer’s disease (AD) is a devastating neurodegenerative disease and the primary cause of dementia, with no cure currently available. The pathogenesis of AD is believed to be primarily driven by Aβ, the principal component of senile plaques. Aβ is an ~4 kDa peptide generated from the amyloid-β precursor protein (APP) through proteolytic secretases. Natural products, particularly those utilized in traditional Chinese medicine (TCM), have a long history alleviating common clinical disorders, including dementia. However, the cell/molecular pathways mediated by these natural products are largely unknown until recently when the underlying molecular mechanisms of the disorders begin to be elucidated. Here, the mechanisms with which natural products modulate the pathogenesis of AD are discussed, in particular, by focusing on their roles in the processing of APP. PMID:22998566

Neurotoxicity of a Fragment of the Amyloid Precursor Associated with Alzheimer's Disease

NASA Astrophysics Data System (ADS)

Yankner, Bruce A.; Dawes, Linda R.; Fisher, Shannon; Villa-Komaroff, Lydia; Oster-Granite, Mary Lou; Neve, Rachael L.

1989-07-01

Amyloid deposition in senile plaques and the cerebral vasculature is a marker of Alzheimer's disease. Whether amyloid itself contributes to the neurodegenerative process or is simply a by-product of that process is unknown. Pheochromocytoma (PC12) and fibroblast (NIH 3T3) cell lines were transfected with portions of the gene for the human amyloid precursor protein. Stable PC12 cell transfectants expressing a specific amyloid-containing fragment of the precursor protein gradually degenerated when induced to differentiate into neuronal cells with nerve growth factor. Conditioned medium from these cells was toxic to neurons in primary hippocampal cultures, and the toxic agent could be removed by immunoabsorption with an antibody directed against the amyloid polypeptide. Thus, a peptide derived from the amyloid precursor may be neurotoxic.

The Primary open-angle glaucoma gene WDR36 functions in ribosomal RNA processing and interacts with the p53 stress–response pathway

PubMed Central

Skarie, Jonathan M.; Link, Brian A.

2008-01-01

Primary open-angle glaucoma (POAG) is a genetically complex neuropathy that affects retinal ganglion cells and is a leading cause of blindness worldwide. WDR36, a gene of unknown function, was recently identified as causative for POAG at locus GLC1G. Subsequent studies found disease-associated variants in control populations, leaving the role of WDR36 in this disease unclear. To address this issue, we determined the function of WDR36. We studied Wdr36 in zebrafish and found it is the functional homolog of yeast Utp21. Utp21 is cell essential and functions in the nucleolar processing of 18S rRNA, which is required for ribosome biogenesis. Evidence for functional homology comes from sequence alignment, ubiquitous expression, sub-cellular localization to the nucleolus and loss-of-function phenotypes that include defects in 18S rRNA processing and abnormal nucleolar morphology. Additionally, we show that loss of Wdr36 function leads to an activation of the p53 stress–response pathway, suggesting that co-inheritance of defects in p53 pathway genes may influence the impact of WDR36 variants on POAG. Although these results overall do not provide evidence for or against a role of WDR36 in POAG, they do provide important baseline information for future studies. PMID:18469340

[Behaviours related to infectious disease and family factors in primary and middle school students].

PubMed

Feng, Na; Luo, Jiayou; Li, Huixia; Zhu, Na; Feng, Qi; Li, Xiongwei; Zhou, Haixiang

2015-06-01

To explore the behaviors related to infectious disease and family factors in primary and middle school students, and to provide evidence for improving behaviors related to infectious disease.
 A total of 8465 students were randomly surveyed by a standard questionnaire of behaviors related to infectious disease. Chi-square test was used to analyze the influential factors for behaviors related to infectious disease, and non conditional logistic regression analysis was used to analyze the multiple factors.
 The total formation rate of behaviors related to infectious disease was 66.4%. The rates for primary and middle school students were 69.4% and 62.8% respectively, with significant difference (P<0.05). There were significant differences in the following behaviors, such as washing hands before eating food, rarely buying snacks on outside stalls, informing teachers when showing infectious disease symptoms (all P<0.05), the degree for such behaviors in primary school students was higher than that in middle school students. There were also significant differences in the following behaviors, such as washing hands after using the toilet, blocking with a handkerchief, wiping while coughing and sneezing (all P<0.05), the degree for such behaviors in middle school students was higher than that in primary school students. Non conditional logistic regression analysis showed that the behaviors related to infectious disease in primary and middle school students were associated with parents' education degree, mother's occupation and living status with parents.
 Behaviors related to infectious disease in primary and middle school students need to be improved, and the formation of these behaviors may be related to many family factors.

Memory and emotion processing performance contributes to the diagnosis of non-semantic primary progressive aphasia syndromes.

PubMed

Piguet, Olivier; Leyton, Cristian E; Gleeson, Liam D; Hoon, Chris; Hodges, John R

2015-01-01

The two non-semantic variants of primary progressive aphasia (PPA), nonfluent/agrammatic PPA (nfv-PPA) and logopenic variant PPA (lv-PPA), share language features despite their different underlying pathology, and may be difficult to distinguish for non-language experts. To improve diagnostic accuracy of nfv-PPA and lv-PPA using tasks measuring non-language cognition and emotion processing. Thirty-eight dementia patients meeting diagnostic criteria for PPA (nfv-PPA 20, lv-PPA 18) and 21 matched healthy Controls underwent a comprehensive assessment of cognition and emotion processing, as well as a high-resolution structural MRI and a PiB-PET scan, a putative biomarker of Alzheimer's disease. Task performances were compared between the groups and those found to differ significantly were entered into a logistic regression analysis. Analyses revealed a double dissociation between nfv-PPA and lv-PPA. nfv-PPA exhibited significant emotion processing disturbance compared to lv-PPA and Controls. In contrast, only the lv-PPA group was significantly impaired on tasks of episodic memory. Logistic regression analyses showed that 87% of patients were correctly classified using emotion processing and episodic memory composite scores, together with a measure of visuospatial ability. Non-language presenting features can help differentiate between the two non-semantic PPA syndromes, with a double dissociation observed on tasks of episodic memory and emotion processing. Based on performance on these tasks, we propose a decision tree as a complementary method to differentiate between the two non-semantic variants. These findings have important clinical implications, with identification of patients who may potentially benefit existing therapeutic interventions currently available for Alzheimer's disease.

Development and pilot test of a process to identify research needs from a systematic review.

PubMed

Saldanha, Ian J; Wilson, Lisa M; Bennett, Wendy L; Nicholson, Wanda K; Robinson, Karen A

2013-05-01

To ensure appropriate allocation of research funds, we need methods for identifying high-priority research needs. We developed and pilot tested a process to identify needs for primary clinical research using a systematic review in gestational diabetes mellitus. We conducted eight steps: abstract research gaps from a systematic review using the Population, Intervention, Comparison, Outcomes, and Settings (PICOS) framework; solicit feedback from the review authors; translate gaps into researchable questions using the PICOS framework; solicit feedback from multidisciplinary stakeholders at our institution; establish consensus among multidisciplinary external stakeholders on the importance of the research questions using the Delphi method; prioritize outcomes; develop conceptual models to highlight research needs; and evaluate the process. We identified 19 research questions. During the Delphi method, external stakeholders established consensus for 16 of these 19 questions (15 with "high" and 1 with "medium" clinical benefit/importance). We pilot tested an eight-step process to identify clinically important research needs. Before wider application of this process, it should be tested using systematic reviews of other diseases. Further evaluation should include assessment of the usefulness of the research needs generated using this process for primary researchers and funders. Copyright © 2013 Elsevier Inc. All rights reserved.

Integrating an infectious disease programme into the primary health care service: a retrospective analysis of Chagas disease community-based surveillance in Honduras.

PubMed

Hashimoto, Ken; Zúniga, Concepción; Nakamura, Jiro; Hanada, Kyo

2015-03-24

Integration of disease-specific programmes into the primary health care (PHC) service has been attempted mostly in clinically oriented disease control such as HIV/AIDS and tuberculosis but rarely in vector control. Chagas disease is controlled principally by interventions against the triatomine vector. In Honduras, after successful reduction of household infestation by vertical approach, the Ministry of Health implemented community-based vector surveillance at the PHC services (health centres) to prevent the resurgence of infection. This paper retrospectively analyses the effects and process of integrating a Chagas disease vector surveillance system into health centres. We evaluated the effects of integration at six pilot sites in western Honduras during 2008-2011 on; surveillance performance; knowledge, attitude and practice in schoolchildren; reports of triatomine bug infestation and institutional response; and seroprevalence among children under 15 years of age. The process of integration of the surveillance system was analysed using the PRECEDE-PROCEED model for health programme planning. The model was employed to systematically determine influential and interactive factors which facilitated the integration process at different levels of the Ministry of Health and the community. Overall surveillance performance improved from 46 to 84 on a 100 point-scale. Schoolchildren's attitude (risk awareness) score significantly increased from 77 to 83 points. Seroprevalence declined from 3.4% to 0.4%. Health centres responded to the community bug reports by insecticide spraying. As key factors, the health centres had potential management capacity and influence over the inhabitants' behaviours and living environment directly and through community health volunteers. The National Chagas Programme played an essential role in facilitating changes with adequate distribution of responsibilities, participatory modelling, training and, evaluation and advocacy. We found that Chagas disease vector surveillance can be integrated into the PHC service. Health centres demonstrated capacity to manage vector surveillance and improve performance, children's awareness, vector report-response and seroprevalence, once tasks were simplified to be performed by trained non-specialists and distributed among the stakeholders. Health systems integration requires health workers to perform beyond their usual responsibilities and acquire management skills. Integration of vector control is feasible and can contribute to strengthening the preventive capacity of the PHC service.

Multiple Sclerosis: Epidemiologic, Clinical, and Therapeutic Aspects.

PubMed

Vidal-Jordana, Angela; Montalban, Xavier

2017-05-01

Multiple sclerosis (MS) is a chronic autoimmune and degenerative disease of the central nervous system that affects young people. MS develops in genetically susceptible individuals exposed to different unknown triggering factors. Different phenotypes are described. About 15% of patients present with a primary progressive course and 85% with a relapsing-remitting course. An increasing number of disease-modifying treatments has emerged. Although encouraging, the number of drugs challenges the neurologist because each treatment has its own risk-benefit profile. Patients should be involved in the decision-making process to ensure good treatment and safety monitoring adherence. Copyright © 2016 Elsevier Inc. All rights reserved.

The Proteasome and Oxidative Stress in Alzheimer's Disease.

PubMed

Bonet-Costa, Vicent; Pomatto, Laura Corrales-Diaz; Davies, Kelvin J A

2016-12-01

Alzheimer's disease is a neurodegenerative disorder that is projected to exceed more than 100 million cases worldwide by 2050. Aging is considered the primary risk factor for some 90% of Alzheimer's cases but a significant 10% of patients suffer from aggressive, early-onset forms of the disease. There is currently no effective Alzheimer's treatment and this, coupled with a growing aging population, highlights the necessity to understand the mechanism(s) of disease initiation and propagation. A major hallmark of Alzheimer's disease pathology is the accumulation of amyloid-β (Aβ) aggregates (an early marker of Alzheimer's disease), and neurofibrillary tangles, comprising the hyper-phosphorylated microtubule-associated protein Tau. Recent Advances: Protein oxidation is frequently invoked as a potential factor in the progression of Alzheimer's disease; however, whether it is a cause or a consequence of the pathology is still being debated. The Proteasome complex is a major regulator of intracellular protein quality control and an essential proteolytic enzyme for the processing of both Aβ and Tau. Recent studies have indicated that both protein oxidation and excessive phosphorylation may limit Proteasomal processing of Aβ and Tau in Alzheimer's disease. Thus, the Proteasome may be a key factor in understanding the development of Alzheimer's disease pathology; however, its significance is still very much under investigation. Discovering how the proteasome is affected, regulated, or dysregulated in Alzheimer's disease could be a valuable tool in the efforts to understand and, ultimately, eradicate the disease. Antioxid. Redox Signal. 25, 886-901.

Tuberculosis as a three-act play: A new paradigm for the pathogenesis of pulmonary tuberculosis.

PubMed

Hunter, Robert L

2016-03-01

Lack of access to human tissues with untreated tuberculosis (TB) has forced generations of researchers to use animal models and to adopt a paradigm that granulomas are the characteristic lesion of both primary and post primary TB. An extended search of studies of human lung tissues failed to find any reports that support this paradigm. We found scores of publications from gross pathology in 1804 through high resolution CT scans in 2015 that identify obstructive lobular pneumonia, not granulomas, as the characteristic lesion of developing post-primary TB. This paper reviews this literature together with other relevant observations to formulate a new paradigm of TB with three distinct stages: a three-act play. First, primary TB, a war of attrition, begins with infection that spreads via lymphatics and blood stream before inducing systemic immunity that contains and controls the organisms within granulomas. Second, post-primary TB, a sneak attack, develops during latent TB as an asymptomatic obstructive lobular pneumonia in persons with effective systemic immunity. It is a paucibacillary process with no granulomas that spreads via bronchi and accumulates mycobacterial antigens and host lipids for 1-2 years before suddenly undergoing caseous necrosis. Third, the fallout, is responsible for nearly all clinical post primary disease. It begins with caseous necrotic pneumonia that is either retained to become the focus of fibrocaseous disease or is coughed out to leave a cavity. This three-stage paradigm suggests testable hypotheses and plausible answers to long standing questions of immunity to TB. Copyright © 2015 The Author. Published by Elsevier Ltd.. All rights reserved.

Series: The research agenda for general practice/family medicine and primary health care in Europe. Part 2. Results: Primary care management and community orientation.

PubMed

Hummers-Pradier, Eva; Beyer, Martin; Chevallier, Patrick; Eilat-Tsanani, Sophia; Lionis, Christos; Peremans, Lieve; Petek, Davorina; Rurik, Imre; Soler, Jean Karl; Stoffers, Henri Ejh; Topsever, Pinar; Ungan, Mehmet; van Royen, Paul

2010-03-01

At the WONCA Europe conference 2009 the recently published 'Research Agenda for General Practice/Family Medicine and Primary Health Care in Europe' was presented. It is a background paper and reference manual, providing advocacy of general practice/family medicine (GP/FM) in Europe. The Research Agenda summarizes the evidence relating to the core competencies and characteristics of the WONCA Europe definition of GP/FM, and its implications for general practitioners/family doctors, researchers and policy makers. The European Journal of General Practice publishes a series of articles based on this document. In a first article, background, objectives, and methodology were discussed. In this second article, the results for the core competencies 'primary care management' and 'community orientation' are presented. Though there is a large body of research on various aspects of 'primary care management', it represents a very scattered rather than a meta view. Many studies focus on care for specific diseases, the primary/secondary care interface, or the implications of electronic patient records. Cost efficiency or process indicators of quality are current outcomes. Current literature on community orientation is mainly descriptive, and focuses on either care for specific diseases, or specific patient populations, or on the uptake of preventive services. Most papers correspond poorly to the WONCA concept. For both core competencies, there is a lack of research with a longitudinal perspective and/or relevant health or quality of life outcomes as well as research on patients' preferences and education for organizational aspects of GP/FM.

Physicians' perceptions of capacity building for managing chronic disease in seniors using integrated interprofessional care models.

PubMed

Lee, Linda; Heckman, George; McKelvie, Robert; Jong, Philip; D'Elia, Teresa; Hillier, Loretta M

2015-03-01

To explore the barriers to and facilitators of adapting and expanding a primary care memory clinic model to integrate care of additional complex chronic geriatric conditions (heart failure, falls, chronic obstructive pulmonary disease, and frailty) into care processes with the goal of improving outcomes for seniors. Mixed-methods study using quantitative (questionnaires) and qualitative (interviews) methods. Ontario. Family physicians currently working in primary care memory clinic teams and supporting geriatric specialists. Family physicians currently working in memory clinic teams (n = 29) and supporting geriatric specialists(n = 9) were recruited as survey participants. Interviews were conducted with memory clinic lead physicians (n = 16).Statistical analysis was done to assess differences between family physician ratings and geriatric specialist ratings related to the capacity for managing complex chronic geriatric conditions, the role of interprofessional collaboration within primary care, and funding and staffing to support geriatric care. Results from both study methods were compared to identify common findings. Results indicate overall support for expanding the memory clinic model to integrate care for other complex conditions. However, the current primary care structure is challenged to support optimal management of patients with multiple comorbidities, particularly as related to limited funding and staffing resources. Structured training, interprofessional teams, and an active role of geriatric specialists within primary care were identified as important facilitators. The memory clinic model, as applied to other complex chronic geriatric conditions, has the potential to build capacity for high-quality primary care, improve health outcomes,promote efficient use of health care resources, and reduce healthcare costs.

Primary Immunodeficiency Diseases: An Update on the Classification from the International Union of Immunological Societies Expert Committee for Primary Immunodeficiency

PubMed Central

Al-Herz, Waleed; Bousfiha, Aziz; Casanova, Jean-Laurent; Chapel, Helen; Conley, Mary Ellen; Cunningham-Rundles, Charlotte; Etzioni, Amos; Fischer, Alain; Franco, Jose Luis; Geha, Raif S.; Hammarström, Lennart; Nonoyama, Shigeaki; Notarangelo, Luigi Daniele; Ochs, Hans Dieter; Puck, Jennifer M.; Roifman, Chaim M.; Seger, Reinhard; Tang, Mimi L. K.

2011-01-01

We report the updated classification of primary immunodeficiency diseases, compiled by the ad hoc Expert Committee of the International Union of Immunological Societies. As compared to the previous edition, more than 15 novel disease entities have been added in the updated version. For each disorders, the key clinical and laboratory features are provided. This updated classification is meant to help in the diagnostic approach to patients with these diseases. PMID:22566844

18F-FDG PET for staging breast cancer in patients with inner-quadrant versus outer-quadrant tumors: comparison with long-term clinical outcome.

PubMed

Tran, Amy; Pio, Betty S; Khatibi, Bahareh; Czernin, Johannes; Phelps, Michael E; Silverman, Daniel H S

2005-09-01

Extraaxillary metastases (i.e., in the absence of axillary involvement) are more likely to develop in patients with inner-quadrant (IQ) breast cancer than in patients with outer-quadrant (OQ) primary tumors. The relative difficulty of identifying extraaxillary metastases may lead to understaging of cancer in these patients. This study examined whether (18)F-FDG PET findings were differentially associated with the location of primary tumors, and with long-term prognosis, in IQ and OQ patients. Follow-up data were obtained for 141 patients whose breast cancer was staged by PET and who were documented to have IQ (n = 42) or OQ (n = 99) primaries. Results were stratified according to PET findings consistent with different metastatic patterns. Data were further analyzed with respect to disease outcome after a mean 3-y follow-up period. Among IQ patients, progressive disease was identified in 26.1%, compared with 13.1% of OQ patients, for a relative risk (RR) of 2.0. Of patients with PET findings of isolated extraaxillary metastases, 36.1% had progressive disease, compared with 10.7% of other patients (RR = 3.4), and 61.9% of IQ patients had isolated extraaxillary metastases identified on PET, compared with 10.1% of OQ patients (RR = 6.1). IQ patients demonstrated a 6-fold greater frequency of PET findings of isolated extraaxillary metastasis, and such findings were associated with triple the risk for disease progression. Patients with IQ tumors could be vulnerable to understaging with conventional staging approaches and may particularly benefit from PET during the staging process.

Genetic Heterogeneity in Therapy-Naïve Synchronous Primary Breast Cancers and Their Metastases.

PubMed

Ng, Charlotte K Y; Bidard, Francois-Clement; Piscuoglio, Salvatore; Geyer, Felipe C; Lim, Raymond S; de Bruijn, Ino; Shen, Ronglai; Pareja, Fresia; Berman, Samuel H; Wang, Lu; Pierga, Jean-Yves; Vincent-Salomon, Anne; Viale, Agnes; Norton, Larry; Sigal, Brigitte; Weigelt, Britta; Cottu, Paul; Reis-Filho, Jorge S

2017-08-01

Purpose: Paired primary breast cancers and metachronous metastases after adjuvant treatment are reported to differ in their clonal composition and genetic alterations, but it is unclear whether these differences stem from the selective pressures of the metastatic process, the systemic therapies, or both. We sought to define the repertoire of genetic alterations in breast cancer patients with de novo metastatic disease who had not received local or systemic therapy. Experimental Design: Up to two anatomically distinct core biopsies of primary breast cancers and synchronous distant metastases from nine patients who presented with metastatic disease were subjected to high-depth whole-exome sequencing. Mutations, copy number alterations and their cancer cell fractions, and mutation signatures were defined using state-of-the-art bioinformatics methods. All mutations identified were validated with orthogonal methods. Results: Genomic differences were observed between primary and metastatic deposits, with a median of 60% (range 6%-95%) of shared somatic mutations. Although mutations in known driver genes including TP53, PIK3CA , and GATA3 were preferentially clonal in both sites, primary breast cancers and their synchronous metastases displayed spatial intratumor heterogeneity. Likely pathogenic mutations affecting epithelial-to-mesenchymal transition-related genes, including SMAD4, TCF7L2 , and TCF4 ( ITF2 ), were found to be restricted to or enriched in the metastatic lesions. Mutational signatures of trunk mutations differed from those of mutations enriched in the primary tumor or the metastasis in six cases. Conclusions: Synchronous primary breast cancers and metastases differ in their repertoire of somatic genetic alterations even in the absence of systemic therapy. Mutational signature shifts might contribute to spatial intratumor genetic heterogeneity. Clin Cancer Res; 23(15); 4402-15. ©2017 AACR . ©2017 American Association for Cancer Research.

The Chronic Care Model and Diabetes Management in US Primary Care Settings: A Systematic Review

PubMed Central

Stellefson, Michael; Stopka, Christine

2013-01-01

Introduction The Chronic Care Model (CCM) uses a systematic approach to restructuring medical care to create partnerships between health systems and communities. The objective of this study was to describe how researchers have applied CCM in US primary care settings to provide care for people who have diabetes and to describe outcomes of CCM implementation. Methods We conducted a literature review by using the Cochrane database of systematic reviews, CINAHL, and Health Source: Nursing/Academic Edition and the following search terms: “chronic care model” (and) “diabet*.” We included articles published between January 1999 and October 2011. We summarized details on CCM application and health outcomes for 16 studies. Results The 16 studies included various study designs, including 9 randomized controlled trials, and settings, including academic-affiliated primary care practices and private practices. We found evidence that CCM approaches have been effective in managing diabetes in US primary care settings. Organizational leaders in health care systems initiated system-level reorganizations that improved the coordination of diabetes care. Disease registries and electronic medical records were used to establish patient-centered goals, monitor patient progress, and identify lapses in care. Primary care physicians (PCPs) were trained to deliver evidence-based care, and PCP office–based diabetes self-management education improved patient outcomes. Only 7 studies described strategies for addressing community resources and policies. Conclusion CCM is being used for diabetes care in US primary care settings, and positive outcomes have been reported. Future research on integration of CCM into primary care settings for diabetes management should measure diabetes process indicators, such as self-efficacy for disease management and clinical decision making. PMID:23428085

[Minamata disease: a neuropathological viewpoint].

PubMed

Eto, Komyo

2006-01-01

Minamata disease (methylmercury poisoning) was first officially discovered around Minamata Bay in the Kumamoto Prefecture on May 1st, 1956. This year, a commemoration marking fifty years since this discovery of Minamata disease will be held in Minamata City. Over the years, new facts have gradually surfaced, especially after 1995, with the resolution of the political problems surrounding Minamata disease. For example, it was recently reported that large amounts of methylmercury were generated by the chemical processes of the Chisso acetaldehyde plant and later dumped directly into Minamata Bay. This report revealed the August 1951 switch from using manganese dioxide to ferric sulfide as a reaction promoter to maintain the activity of the Hg catalyst. As a result of this switch, the amount of methylmercury generated in the process rapidly increased. Thus, the true cause of the acute onset of Minamata disease in patients with a high-dose contamination of methylmercury was made clear. The severe contamination by methylmercury continued until 1968, when the plant finally stopped discharging its waste water into Minamata Bay. In 1996, the National Institute for Minamata Disease started an experimental study of methylmercury poisoning using the common marmoset. Results from this study showed that the lesions characteristic of the central nervous system in cases of acute methylmercury poisoning were promoted by brain edema, while those of the peripheral nerves were caused by axonal degeneration. Peripheral nerves were regenerated in two animals after two and a half years. Lesions characteristic of Minamata disease are systematically found throughout the nervous system. These lesions are found in the calcarine areas of occipital lobes, the pre- and post-central lobes, and the temporal transverse gyri. Milder and more diffuse lesions are also found in the cerebrum, where secondary degeneration of the central parts of white matter and internal sagittal stratum are due to primary damage of neurons. Purkinje and granular cells decrease in number in the cerebellum depending on the dose of methylmercury and the duration of methylmercury exposure. In the spinal cord, there is no primary change, but secondary degeneration is found on pyramidal tracts due to damage of the motor neurons of the precentral cortices. Additionally, secondary degeneration of Goll's tract is seen due to the primary degeneration of sensory nerve fibers including ganglion cells, sciatic nerves, and sural nerves. The experiments on the methylmercury-treated common marmosets provided every feature of pathological change found in the nervous system in human autopsy cases, depending on the dose of methylmercury.

Grave's Disease and Primary Biliary Cirrhosis-An Unusual and Challenging Association.

PubMed

Shetty, Shiran; Rajasekaran, Senthilkumar; Venkatakrishnan, Leela

2014-03-01

Jaundice in Grave's diseases is uncommon, but when it does occur, complication of thyrotoxicosis (heart failure/infection) or intrinsic liver disease should be considered. Grave's disease can cause asymptomatic elevation of liver enzymes, jaundice and rarely acute liver failure. It is associated with other autoimmune diseases like autoimmune hepatitis, or primary biliary cirrhosis. The cause of jaundice in Grave's disease is multifactorial.

Grave's Disease and Primary Biliary Cirrhosis—An Unusual and Challenging Association

PubMed Central

Shetty, Shiran; Rajasekaran, Senthilkumar; Venkatakrishnan, Leela

2013-01-01

Jaundice in Grave's diseases is uncommon, but when it does occur, complication of thyrotoxicosis (heart failure/infection) or intrinsic liver disease should be considered. Grave's disease can cause asymptomatic elevation of liver enzymes, jaundice and rarely acute liver failure. It is associated with other autoimmune diseases like autoimmune hepatitis, or primary biliary cirrhosis. The cause of jaundice in Grave's disease is multifactorial. PMID:25755537

From empower to Green Dot : successful strategies and lessons learned in developing comprehensive sexual violence primary prevention programming.

PubMed

Cook-Craig, Patricia G; Millspaugh, Phyllis H; Recktenwald, Eileen A; Kelly, Natalie C; Hegge, Lea M; Coker, Ann L; Pletcher, Tisha S

2014-10-01

This case study describes Kentucky's partnership with the Centers for Disease Control and Prevention (CDC) EMPOWER (Enhancing and Making Programs Work to End Rape) program to enhance the mission and services of existing rape crisis centers to include comprehensive primary prevention programming to reduce rates of sexual violence perpetration. The planning process and the successful implementation of a statewide, 5-year, randomized control trial study of a bystander prevention program (Green Dot), and its evaluation are described. Lessons learned in generating new questions, seeking funding, building relationships and capacity, and disseminating knowledge are presented. © The Author(s) 2014.

Primary and Secondary Prevention of Acute Coronary Syndromes: The Role of the Statins.

PubMed

Diamantis, Evangelos; Troupis, Theodoros; Mazarakis, Antonios; Kyriakos, Giorgos; Diamanti, S; Troupis, Georgios; Skandalakis, Panagiotis

2014-01-01

Poor prognosis is strongly associated with Acute Coronary Syndrome (ACS) and, even though a number of treatment strategies are available, the incidence of subsequent serious complications after an acute event is still high. Statins are hypolipidemic factors and recent studies have demonstrated that they have a protective role during the process of atherogenesis and that they reduce mortality caused by cardiovascular diseases. This review tries to reveal the function of the statins as a component of the primary and secondary action of acute coronary syndrome and to describe the lifestyle changes that have the same effect as the use of statins.

Exercise Promotes Healthy Aging of Skeletal Muscle

PubMed Central

Cartee, Gregory D.; Hepple, Russell T.; Bamman, Marcas M.; Zierath, Juleen R.

2016-01-01

Primary aging is the progressive and inevitable process of bodily deterioration during adulthood. In skeletal muscle, primary aging causes defective mitochondrial energetics, and reduced muscle mass. Secondary aging refers to additional deleterious structural and functional age-related changes caused by diseases and lifestyle factors. Secondary aging can exacerbate deficits in mitochondrial function and muscle mass, concomitant with the development of skeletal muscle insulin resistance. Exercise opposes deleterious effects of secondary aging by preventing the decline in mitochondrial respiration, mitigating aging-related loss of muscle mass and enhancing insulin sensitivity. This review focuses on mechanisms by which exercise promotes “healthy aging” by inducing modifications in skeletal muscle. PMID:27304505

Oxidative Stress in Kidney Diseases: The Cause or the Consequence?

PubMed

Krata, Natalia; Zagożdżon, Radosław; Foroncewicz, Bartosz; Mucha, Krzysztof

2018-06-01

Exaggerated oxidative stress (OS) is usually considered as a disturbance in regular function of an organism. The excessive levels of OS mediators may lead to major damage within the organism's cells and tissues. Therefore, the OS-associated biomarkers may be considered as new diagnostic tools of various diseases. In nephrology, researchers are looking for alternative methods replacing the renal biopsy in patients with suspicion of chronic kidney disease (CKD). Currently, CKD is a frequent health problem in world population, which can lead to progressive loss of kidney function and eventually to end-stage renal disease. The course of CKD depends on the primary disease. It is assumed that one of the factors influencing the course of CKD might be OS. In the current work, we review whether monitoring the OS-associated biomarkers in nephrology patients can support the decision-making process regarding diagnosis, prognostication and treatment initiation.

Glycogen Synthase Kinase-3 (GSK3): Inflammation, Diseases, and Therapeutics

PubMed Central

Jope, Richard S.; Yuskaitis, Christopher J.; Beurel, Eléonore

2007-01-01

Deciphering what governs inflammation and its effects on tissues is vital for understanding many pathologies. The recent discovery that glycogen synthase kinase-3 (GSK3) promotes inflammation reveals a new component of its well-documented actions in several prevalent diseases which involve inflammation, including mood disorders, Alzheimer’s disease, diabetes, and cancer. Involvement in such disparate conditions stems from the widespread influences of GSK3 on many cellular functions, with this review focusing on its regulation of inflammatory processes. GSK3 promotes the production of inflammatory molecules and cell migration, which together make GSK3 a powerful regulator of inflammation, while GSK3 inhibition provides protection from inflammatory conditions in animal models. The involvement of GSK3 and inflammation in these diseases are highlighted. Thus, GSK3 may contribute not only to primary pathologies in these diseases, but also to the associated inflammation, suggesting that GSK3 inhibitors may have multiple effects influencing these conditions. PMID:16944320

Transfer RNA and human disease.

PubMed

Abbott, Jamie A; Francklyn, Christopher S; Robey-Bond, Susan M

2014-01-01

Pathological mutations in tRNA genes and tRNA processing enzymes are numerous and result in very complicated clinical phenotypes. Mitochondrial tRNA (mt-tRNA) genes are "hotspots" for pathological mutations and over 200 mt-tRNA mutations have been linked to various disease states. Often these mutations prevent tRNA aminoacylation. Disrupting this primary function affects protein synthesis and the expression, folding, and function of oxidative phosphorylation enzymes. Mitochondrial tRNA mutations manifest in a wide panoply of diseases related to cellular energetics, including COX deficiency (cytochrome C oxidase), mitochondrial myopathy, MERRF (Myoclonic Epilepsy with Ragged Red Fibers), and MELAS (mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes). Diseases caused by mt-tRNA mutations can also affect very specific tissue types, as in the case of neurosensory non-syndromic hearing loss and pigmentary retinopathy, diabetes mellitus, and hypertrophic cardiomyopathy. Importantly, mitochondrial heteroplasmy plays a role in disease severity and age of onset as well. Not surprisingly, mutations in enzymes that modify cytoplasmic and mitochondrial tRNAs are also linked to a diverse range of clinical phenotypes. In addition to compromised aminoacylation of the tRNAs, mutated modifying enzymes can also impact tRNA expression and abundance, tRNA modifications, tRNA folding, and even tRNA maturation (e.g., splicing). Some of these pathological mutations in tRNAs and processing enzymes are likely to affect non-canonical tRNA functions, and contribute to the diseases without significantly impacting on translation. This chapter will review recent literature on the relation of mitochondrial and cytoplasmic tRNA, and enzymes that process tRNAs, to human disease. We explore the mechanisms involved in the clinical presentation of these various diseases with an emphasis on neurological disease.

Lung capillary injury and repair in left heart disease: a new target for therapy?

PubMed

Azarbar, Sayena; Dupuis, Jocelyn

2014-07-01

The lungs are the primary organs affected in LHD (left heart disease). Increased left atrial pressure leads to pulmonary alveolar-capillary stress failure, resulting in cycles of alveolar wall injury and repair. The reparative process causes the proliferation of MYFs (myofibroblasts) with fibrosis and extracellular matrix deposition, resulting in thickening of the alveolar wall. Although the resultant reduction in vascular permeability is initially protective against pulmonary oedema, the process becomes maladaptive causing a restrictive lung syndrome with impaired gas exchange. This pathological process may also contribute to PH (pulmonary hypertension) due to LHD. Few clinical trials have specifically evaluated lung structural remodelling and the effect of related therapies in LHD. Currently approved treatment for chronic HF (heart failure) may have direct beneficial effects on lung structural remodelling. In the future, novel therapies specifically targeting the remodelling processes may potentially be utilized. In the present review, we summarize data supporting the clinical importance and pathophysiological mechanisms of lung structural remodelling in LHD and propose that this pathophysiological process should be explored further in pre-clinical studies and future therapeutic trials.

[The mean timing of periodontic care rendering].

PubMed

Zorina, O A; Abaev, Z M; Domashev, D I; Boriskina, O A

2012-01-01

The time-studies demonstrated that the periodontologist spend 30.3 +/- 2.6 minutes on the primary ambulatory visit of patient and 16.4 +/- 0.9 minutes on the revisit of patient (non-registering time spending on preventive and curative activities). Time spending on curative preventive activities in each group of patients with periodontal diseases depended on both the severity of inflammatory destructive processes in periodontium and therapy stage.

What drives quality improvement in chronic kidney disease (CKD) in primary care: process evaluation of the Quality Improvement in Chronic Kidney Disease (QICKD) trial.

PubMed

Nihat, Akin; de Lusignan, Simon; Thomas, Nicola; Tahir, Mohammad Aumran; Gallagher, Hugh

2016-04-06

This study is a process evaluation of the Quality Improvement in Chronic Kidney Disease (QICKD) study, comparing audit-based education (ABE) and sending clinical guidelines and prompts (G&P) with usual practice, in improving systolic blood pressure control in primary care. This evaluation aimed to explore how far clinical staff in participating practices were aware of the intervention, and why change in practice might have taken place. 4 primary care practices in England: 2 received ABE, and 2 G&P. We purposively selected 1 northern/southern/city and rural practice from each study arm (from a larger pool of 132 practices as part of the QICKD trial). The 4 study practices were purposively sampled, and focus groups conducted with staff from each. All staff members were invited to attend. Focus groups in each of 4 practices, at the mid-study point and at the end. 4 additional trial practices not originally selected for in-depth process evaluation took part in end of trial focus groups, to a total of 12 focus groups. These were recorded, transcribed and analysed using the framework approach. 5 themes emerged: (1) involvement in the study made participants more positive about the CKD register; (2) clinicians did not always explain to patients that they had CKD; (3) while practitioners improved their monitoring of CKD, many were sceptical that it improved care and were more motivated by pay-for-performance measures; (4) the impact of study interventions on practice was generally positive, particularly the interaction with specialists, included in ABE; (5) the study stimulated ideas for future clinical practice. Improving quality in CKD is complex. Lack of awareness of clinical guidelines and scepticism about their validity are barriers to change. While pay-for-performance incentives are the main driver for change, quality improvement interventions can have a complementary influence. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Immunoglobulin A Nephropathy: Advances in Understanding of Pathogenesis and Treatment.

PubMed

Lafayette, Richard A; Kelepouris, Ellie

2018-05-31

Immunoglobulin A (IgA) nephropathy is the most common form of primary glomerulonephritis and has clinical associations with a wide range of inflammatory and infectious diseases. There is a substantial variation in clinical course and outcomes, with many patients not diagnosed until they present with sequelae, which may include gross hematuria, hypertension, renal insufficiency, and/or significant proteinuria. Treatment options are currently limited and directed mainly toward control of these sequelae and have limited ability to reduce the incidence of end-stage renal disease or treat the primary IgA defect. Growing knowledge about the pathogenesis of IgA nephropathy and research into its genetic basis are helping to elucidate the course of this widely variable disease. IgA accumulation in the kidneys is thought to be the result of a number of different pathways in a "multi-hit" process that includes an initial traumatic trigger (often infection related) and subsequent memory responses that are amplified in those with a genetic predisposition to the disease and lead to an inflammatory response in susceptible individuals. Genome-wide association studies are providing new insights into the genetic variance of this autoimmune disease and are yielding information that may address both its causes and consequences. Key Messages: New treatment approaches are urgently required for the management of patients with IgA nephropathy. Novel interventions based around its inflammatory nature and "multi-hit" pathogenesis are being investigated to potentially limit disease progression. © 2018 S. Karger AG, Basel.

Prevalence of Trypanosoma cruzi infection among Bolivian immigrants in the city of São Paulo, Brazil

PubMed Central

Luna, Expedito JA; Furucho, Celia R; Silva, Rubens A; Wanderley, Dalva M; Carvalho, Noemia B; Satolo, Camila G; Leite, Ruth M; Silveira, Cassio; Silva, Lia MB; Aith, Fernando M; Carneiro, Nivaldo; Shikanai-Yasuda, Maria A

2016-01-01

With the urbanisation of the population in developing countries and the process of globalisation, Chagas has become an emerging disease in the urban areas of endemic and non-endemic countries. In 2006, it was estimated that the prevalence of Chagas disease among the general Bolivian population was 6.8%. The aim of the present study was to determine the prevalence of Trypanosoma cruzi infection among Bolivian immigrants living in São Paulo, Brazil. This study had a sample of 633 volunteers who were randomly selected from the clientele of primary care units located in the central districts of São Paulo, Brazil. Infection was detected by two different ELISA assays with epimastigote antigens, followed by an immunoblot with trypomastigote antigens as a confirmatory test. The prevalence of the infection was 4.4%. Risk factors independently associated with the infection were: a history of rural jobs in Bolivia, knowledge of the vector involved in transmission, and having relatives with Chagas disease. Brazil has successfully eliminated household vector transmission of T. cruzi, as well as its transmission by blood transfusion. The arrival of infected immigrants represents an additional challenge to primary care clinics to manage chronic Chagas disease, its vertical transmission, and the blood derivatives and organ transplant programs. PMID:27849221

Prevalence of Trypanosoma cruzi infection among Bolivian immigrants in the city of São Paulo, Brazil.

PubMed

Luna, Expedito Ja; Furucho, Celia R; Silva, Rubens A; Wanderley, Dalva M; Carvalho, Noemia B; Satolo, Camila G; Leite, Ruth M; Silveira, Cassio; Silva, Lia Mb; Aith, Fernando M; Carneiro, Nivaldo; Shikanai-Yasuda, Maria A

2017-01-01

With the urbanisation of the population in developing countries and the process of globalisation, Chagas has become an emerging disease in the urban areas of endemic and non-endemic countries. In 2006, it was estimated that the prevalence of Chagas disease among the general Bolivian population was 6.8%. The aim of the present study was to determine the prevalence of Trypanosoma cruzi infection among Bolivian immigrants living in São Paulo, Brazil. This study had a sample of 633 volunteers who were randomly selected from the clientele of primary care units located in the central districts of São Paulo, Brazil. Infection was detected by two different ELISA assays with epimastigote antigens, followed by an immunoblot with trypomastigote antigens as a confirmatory test. The prevalence of the infection was 4.4%. Risk factors independently associated with the infection were: a history of rural jobs in Bolivia, knowledge of the vector involved in transmission, and having relatives with Chagas disease. Brazil has successfully eliminated household vector transmission of T. cruzi, as well as its transmission by blood transfusion. The arrival of infected immigrants represents an additional challenge to primary care clinics to manage chronic Chagas disease, its vertical transmission, and the blood derivatives and organ transplant programs.

Obesity: a chronic relapsing progressive disease process. A position statement of the World Obesity Federation.

PubMed

Bray, G A; Kim, K K; Wilding, J P H

2017-07-01

This paper considers the argument for obesity as a chronic relapsing disease process. Obesity is viewed from an epidemiological model, with an agent affecting the host and producing disease. Food is the primary agent, particularly foods that are high in energy density such as fat, or in sugar-sweetened beverages. An abundance of food, low physical activity and several other environmental factors interact with the genetic susceptibility of the host to produce positive energy balance. The majority of this excess energy is stored as fat in enlarged, and often more numerous fat cells, but some lipid may infiltrate other organs such as the liver (ectopic fat). The enlarged fat cells and ectopic fat produce and secrete a variety of metabolic, hormonal and inflammatory products that produce damage in organs such as the arteries, heart, liver, muscle and pancreas. The magnitude of the obesity and its adverse effects in individuals may relate to the virulence or toxicity of the environment and its interaction with the host. Thus, obesity fits the epidemiological model of a disease process except that the toxic or pathological agent is food rather than a microbe. Reversing obesity will prevent most of its detrimental effects. © 2017 World Obesity Federation.

GATA3 expression in primary vulvar Paget disease: a potential pitfall leading to misdiagnosis of pagetoid urothelial intraepithelial neoplasia.

PubMed

Morbeck, Diogo; Tregnago, Aline C; Baiocchi, Glauco; Sacomani, Carlos; Peresi, Patricia M; Osório, Cynthia T; Schutz, Luciana; Bezerra, Stephania M; de Brot, Louise; Cunha, Isabela W

2017-02-01

GATA3 has been reported as a specific urothelial marker among organs in the pelvic region, and has been classified as highly sensitive and specific for urothelial and breast carcinomas. Our aim was to verify GATA3 expression in extramammary Paget disease, and to determine whether it can be use to differentiate primary vulvar Paget disease from pagetoid urothelial intraepithelial neoplasia (PUIN). We also analysed HER2 protein expression and HER2 gene amplification and their roles as prognostic factors in extramammary Paget disease. We analysed GATA3 and HER2 expression in 11 primary vulvar Paget disease cases and two PUIN cases. All cases showed nuclear expression of GATA3. Of 13 cases, five were equivocal for HER2 expression (score 2+) and one was positive (3+). Fluorescence in-situ hybridization results showed amplification in two of these six cases. Both HER2-amplified cases were invasive. GATA3 was positive in all extramammary Paget disease cases tested (13 cases), and it has no value for differentiating between primary and secondary vulvar Paget disease from the urological tract. HER2 amplification might confer an aggressive and invasive pattern in primary vulvar Paget disease, as both amplified cases showed an invasive pattern. © 2016 John Wiley & Sons Ltd.

Primary Adult Renal Ewing's Sarcoma: A Rare Entity

PubMed Central

Mukkunda, Ravindra; Venkitaraman, Ramachandran; Thway, Khin; Min, Toon; Fisher, Cyril; Horwich, Alan; Judson, Ian

2009-01-01

Background. Ewing's sarcoma of extraskeletal origin is uncommon and that is of primary renal origin in adults are rare. There is no consensus on the optimal management of Ewing's tumors of renal origin. Methods. A retrospective review of the clinical features, treatment, and outcome of adult patients with primary renal extra-skeletal Ewing's sarcoma who were treated at the Royal Marsden hospital from January 1993–December 2007 is reported. Results. Seven adult patients with primary renal Ewing's sarcoma were identified. All four patients with nonmetastatic disease had radical nephrectomy and received adjuvant chemotherapy +/− radiotherapy. Two developed metastatic disease while on adjuvant chemotherapy, and one patient relapsed after 55 months. The three patients with metastatic disease at presentation did not have nephrectomy and were treated with chemotherapy. All three patients had disease progression with a dismal outcome. Only one patient in the whole group is alive and disease free. The median overall survival was 62.8 months, and the median disease-free survival in patients with nonmetastatic disease after combined modality treatment was 30.3 months. Conclusion. Primary adult renal Ewing's sarcoma is an aggressive tumor with a propensity for early metastasis. Radical nephrectomy with adjuvant combination chemotherapy produced the best results but the outlook remained poor with only one patient experiencing long disease-free survival. PMID:19478963

Global Health and Primary Care: Increasing Burden of Chronic Diseases and Need for Integrated Training

PubMed Central

Truglio, Joseph; Graziano, Michelle; Vedanthan, Rajesh; Hahn, Sigrid; Rios, Carlos; Hendel-Paterson, Brett; Ripp, Jonathan

2015-01-01

Noncommunicable diseases, including cardiovascular disease, chronic respiratory disease, diabetes, cancer, and mental illness, are the leading causes of death and disability worldwide. These diseases are chronic and often mediated predominantly by social determinants of health. Currently there exists a global-health workforce crisis and a subsequent disparity in the distribution of providers able to manage chronic noncommunicable diseases. Clinical competency in global health and primary care could provide practitioners with the knowledge and skills needed to address the global rise of noncommunicable diseases through an emphasis on these social determinants. The past decade has seen substantial growth in the number and quality of US global-health and primary-care training programs, in both undergraduate and graduate medical education. Despite their overlapping competencies, these 2 complementary fields are most often presented as distinct disciplines. Furthermore, many global-health training programs suffer from a lack of a formalized curriculum. At present, there are only a few examples of well-integrated US global-health and primary-care training programs. We call for universal acceptance of global health as a core component of medical education and greater integration of global-health and primary-care training programs in order to improve the quality of each and increase a global workforce prepared to manage noncommunicable diseases and their social mediators. PMID:22786735

Does enrollment in multidisciplinary team-based primary care practice improve adherence to guideline-recommended processes of care? Quebec's Family Medicine Groups, 2002-2010.

PubMed

Diop, Mamadou; Fiset-Laniel, Julie; Provost, Sylvie; Tousignant, Pierre; Borgès Da Silva, Roxane; Ouimet, Marie-Jo; Latimer, Eric; Strumpf, Erin

2017-04-01

We investigated whether multidisciplinary team-based primary care practice improves adherence to process of care guidelines, in the absence of financial incentives related to pay-for-performance. We conducted a natural experiment including 135,119 patients, enrolled with a general practitioner (GP) in a multidisciplinary team Family Medicine Group (FMG) or non-FMG practice, using longitudinal data from Quebec's universal insurer over the relevant time period (2000-2010). All study subjects had diabetes, chronic obstructive pulmonary disease, or heart failure and were followed over a 7-year period, 2 years prior to enrollment and 5 years after. We constructed indicators on adherence to disease-specific guidelines and composite indicators across conditions. We evaluated the effect of FMGs using propensity score methods and Difference-in-Differences (DD) models. Rates of adherence to chronic disease guidelines increased for both FMG and non-FMG patients after enrollment, but not differentially so. Adherence to prescription-related guidelines improved less for FMG patients (DD [95% CI]=-2.83% [-4.08%, -1.58%]). We found no evidence of an FMG effect on adherence to consultation-related guidelines, (DD [95% CI]=-0.24% [-2.24%; 1.75%]). We found no evidence that FMGs increased adherence to the guidelines we evaluated. Future research is needed to assess why this reform did not improve performance on these quality-of-care indicators. Copyright © 2017 Elsevier B.V. All rights reserved.

INCREASING PREVALENCE OF ADDISON DISEASE: RESULTS FROM A NATIONWIDE STUDY.

PubMed

Olafsson, Andri Snaer; Sigurjonsdottir, Helga Agusta

2016-01-01

Primary adrenal insufficiency is a life-threatening endocrine disease unless properly treated. However, few studies on the prevalence, concomitances of the disease, and prescribing of drugs have been published. The goal of the study was to establish the prevalence of primary adrenal insufficiency in Iceland and additionally, to study the most common concomitant diseases in patients with primary adrenal insufficiency, as well as the mode of glucocorticoid replacement therapies. To achieve this, the medical records of all patients in Iceland who had received the International Classification of Diseases and Related Health Problems, 10th Revision, diagnosis code E27, were evaluated for true primary adrenal insufficiency. Additionally, these records were evaluated for concomitant diseases, as well as the mode of glucocorticoid replacement therapy. The study covered the whole population of Iceland over 18 years of age. It was thus a nationwide study. The records were retrieved from large hospitals and clinics and every practicing specialist in endocrinology. Primary adrenal insufficiency was found in 53 individuals, 26 women and 27 men, yielding a prevalence of 22.1 per 100,000 population. Hypothyroidism was by far the most common concomitant disease. Most patients had their glucocorticoid deficiency replaced with short-acting glucocorticoids. The prevalence of primary adrenal insufficiency in Iceland is higher than in earlier reports, with comorbidities being in line with recent studies. Treatment is according to the latest protocols.

Host responses in tissue repair and fibrosis.

PubMed

Duffield, Jeremy S; Lupher, Mark; Thannickal, Victor J; Wynn, Thomas A

2013-01-24

Myofibroblasts accumulate in the spaces between organ structures and produce extracellular matrix (ECM) proteins, including collagen I. They are the primary "effector" cells in tissue remodeling and fibrosis. Previously, leukocyte progenitors termed fibrocytes and myofibroblasts generated from epithelial cells through epithelial-to-mesenchymal transition (EMT) were considered the primary sources of ECM-producing myofibroblasts in injured tissues. However, genetic fate mapping experiments suggest that mesenchyme-derived cells, known as resident fibroblasts, and pericytes are the primary precursors of scar-forming myofibroblasts, whereas epithelial cells, endothelial cells, and myeloid leukocytes contribute to fibrogenesis predominantly by producing key fibrogenic cytokines and by promoting cell-to-cell communication. Numerous cytokines derived from T cells, macrophages, and other myeloid cell populations are important drivers of myofibroblast differentiation. Monocyte-derived cell populations are key regulators of the fibrotic process: They act as a brake on the processes driving fibrogenesis, and they dismantle and degrade established fibrosis. We discuss the origins, modes of activation, and fate of myofibroblasts in various important fibrotic diseases and describe how manipulation of macrophage activation could help ameliorate fibrosis.

Systematic Age-Related Differences in Chronic Disease Management in a Population-Based Cohort Study: A New Paradigm of Primary Care Is Required

PubMed Central

Buja, Alessandra; Damiani, Gianfranco; Gini, Rosa; Visca, Modesta; Federico, Bruno; Donato, Daniele; Francesconi, Paolo; Marini, Alessandro; Donatini, Andrea; Brugaletta, Salvatore; Baldo, Vincenzo; Donata Bellentani, Maria

2014-01-01

Background Our interest in chronic conditions is due to the fact that, worldwide, chronic diseases have overtaken infectious diseases as the leading cause of death and disability, so their management represents an important challenge for health systems. The aim of this study was to compare the performance of primary health care services in managing diabetes, congestive heart failure (CHF) and coronary heart disease (CHD), by age group. Methods This population-based retrospective cohort study was conducted in Italy, enrolling 1,948,622 residents ≥16 years old. A multilevel regression model was applied to analyze compliance to care processes with explanatory variables at both patient and district level, using age group as an independent variable, and adjusting for sex, citizenship, disease duration, and Charlson index on the first level, and for District Health Unit on the second level. Results The quality of chronic disease management showed an inverted U-shaped relationship with age. In particular, our findings indicate lower levels for young adults (16–44 year-olds), adults (45–64), and oldest old (+85) than for patients aged 65–74 in almost all quality indicators of CHD, CHF and diabetes management. Young adults (16–44 y), adults (45–64 y), the very old (75–84 y) and the oldest old (+85 y) patients with CHD, CHF and diabetes are less likely than 65–74 year-old patients to be monitored and treated using evidence-based therapies, with the exceptions of echocardiographic monitoring for CHF in young adult patients, and renal monitoring for CHF and diabetes in the very old. Conclusion Our study shows that more effort is needed to ensure that primary health care systems are sensitive to chronic conditions in the young and in the very elderly. PMID:24632818

Economic evaluation of the practical approach to lung health and informal provider interventions for improving the detection of tuberculosis and chronic airways disease at primary care level in Malawi: study protocol for cost-effectiveness analysis.

PubMed

Gama, Elvis; Madan, Jason; Banda, Hastings; Squire, Bertie; Thomson, Rachael; Namakhoma, Ireen

2015-01-08

Chronic airway diseases pose a big challenge to health systems in most developing countries, particularly in Sub-Saharan Africa. A diagnosis for people with chronic or persistent cough is usually delayed because of individual and health system barriers. However, delayed diagnosis and treatment facilitates further transmission, severity of disease with complications and mortality. The objective of this study is to assess the cost-effectiveness of the practical approach to lung health strategy, a patient-centred approach for diagnosis and treatment of common respiratory illnesses in primary healthcare settings, as a means of strengthening health systems to improve the quality of management of respiratory diseases. Economic evaluation nested in a cluster randomised controlled trial with three arms will be performed. Measures of effectiveness and costs for all arms of the study will be obtained from the cluster randomised controlled clinical trial. The main outcome measures are a combined rate of major respiratory diseases milestones and process indicators extracted from the practical approach to lung health strategy. For analysis, descriptive as well as regression techniques will be used. A cost-effectiveness analysis will be performed according to intention-to-treat principle and from a societal perspective. Cost-effectiveness ratios will be calculated using bootstrapping techniques. We hope to demonstrate the cost-effectiveness of the practical approach to lung health and informal healthcare providers, see an improvement in patients' quality of life, achieve a reduction in the duration and occurrence of episodes and the chronicity of respiratory diseases, and are able to report a decrease in the social cost. If the practical approach to lung health and informal healthcare provider's interventions are cost-effective, they could be scaled up to all primary healthcare centres. PACTR: PACTR201411000910192.

TDP-43 is a culprit in human neurodegeneration, and not just an innocent bystander

PubMed Central

Banks, Gareth T.; Kuta, Anna; Isaacs, Adrian M.

2008-01-01

In 2006 the protein TDP-43 was identified as the major ubiquitinated component deposited in the inclusion bodies found in two human neurodegenerative diseases, amyotrophic lateral sclerosis and frontotemporal lobar degeneration. The pathogenesis of both disorders is unclear, although they are related by having some overlap of symptoms and now by the shared histopathology of TDP-43 deposition. Now, in 2008, several papers have been published in quick succession describing mutations in the TDP-43 gene, showing they can be a primary cause of amyotrophic lateral sclerosis. There are many precedents in neurodegenerative disease in which rare single-gene mutations have given great insight into understanding disease processes, which is why the TDP-43 mutations are potentially very important. PMID:18592312

Ulcerative colitis associated with primary biliary cirrhosis.

PubMed

Koulentaki, M; Koutroubakis, I E; Petinaki, E; Tzardi, M; Oekonomaki, H; Mouzas, I; Kouroumalis, E A

1999-10-01

Primary biliary cirrhosis and ulcerative colitis are two diseases with many features of autoimmunity. Thirteen cases of coexistence of the two diseases have been reported in the literature so far. Patients are usually younger and more often males than the ordinary primary biliary cirrhosis patient, while the colitis is mild and easily controllable. In a homogeneous population of 550,000 inhabitants of the island of Crete, 412 cases of ulcerative colitis and 82 individuals with primary biliary cirrhosis or autoimmune cholangitis have been identified. In two cases, coexistence of the two diseases was found. Immunological screening for AMA positivity in 150 ulcerative colitis sera disclosed no further cases. Prevalence of primary biliary cirrhosis in ulcerative colitis patients seems at least 30 times higher than in the general population in our area. A possible immunological link between the two diseases is discussed.

Intracardiac thrombi in extracardiac disorders: an autopsy study.

PubMed

Vaideeswar, Pradeep; Divate, Smita; Harke, Megha

2012-01-01

Intracardiac thrombi (ICT), more commonly encountered at autopsy, are well documented with underlying cardiovascular disease. Occurrence of ICT in systemic diseases without an intrinsic cardiac disorder is rare. The aim of this autopsy study was to highlight such an occurrence. From 1996 to 2010, cases with ICT unrelated to primary cardiac disorders were selected at autopsy and analyzed. Clinical and investigational data were obtained from the medical records. The location, morphology, size, and histological appearance of the thrombi were noted. The thrombi were then classified on the basis of their location, nature, and histology (fresh and/or organized); this was correlated with the clinical setting. Among a total of 11,724 autopsies performed in 15 years, 276 patients (2.4%) had ICT. Of these, 45 patients (0.4%) had ICT that were unrelated to primary cardiac diseases. There were 25 men and 20 women with a mean age of 46.1 years. Antemortem diagnosis was not made in any of these patients. Eight patients each (35.6%) showed isolated left-sided and multichambered involvement, while the rest of the hearts (64.4%) had thrombi in the right-sided chamber(s). The recognizable risk factors were underlying cancers (24.4%), prolonged immobilization (20%), systemic lupus erythematosus (6.7%), pregnancy (4.4%), nephropathy (4.4%), primary antiphospholipid antibody syndrome (2.2%), and ulcerative colitis (2.2%). However, 16 patients (35.7%) had no obvious predisposing factor, although investigations for prothrombotic markers had not been done. Diabetes mellitus, chronic alcoholism, and deep vein thrombosis of the lower limbs had been clinically documented in some of them. The cause of death in most patients (73.3%) had been related to pulmonary and/or systemic thromboembolism. This autopsy study emphasizes the great need for a higher index of suspicion of in situ thrombosis in the heart in hypercoagulable states so as to curtail the morbidity and mortality of the primary disease process. Copyright © 2012 Elsevier Inc. All rights reserved.

Integrating telecare for chronic disease management in the community: What needs to be done?

PubMed Central

2011-01-01

Background Telecare could greatly facilitate chronic disease management in the community, but despite government promotion and positive demonstrations its implementation has been limited. This study aimed to identify factors inhibiting the implementation and integration of telecare systems for chronic disease management in the community. Methods Large scale comparative study employing qualitative data collection techniques: semi-structured interviews with key informants, task-groups, and workshops; framework analysis of qualitative data informed by Normalization Process Theory. Drawn from telecare services in community and domestic settings in England and Scotland, 221 participants were included, consisting of health professionals and managers; patients and carers; social care professionals and managers; and service suppliers and manufacturers. Results Key barriers to telecare integration were uncertainties about coherent and sustainable service and business models; lack of coordination across social and primary care boundaries, lack of financial or other incentives to include telecare within primary care services; a lack of a sense of continuity with previous service provision and self-care work undertaken by patients; and general uncertainty about the adequacy of telecare systems. These problems led to poor integration of policy and practice. Conclusion Telecare services may offer a cost effective and safe form of care for some people living with chronic illness. Slow and uneven implementation and integration do not stem from problems of adoption. They result from incomplete understanding of the role of telecare systems and subsequent adaption and embeddedness to context, and uncertainties about the best way to develop, coordinate, and sustain services that assist with chronic disease management. Interventions are therefore needed that (i) reduce uncertainty about the ownership of implementation processes and that lock together health and social care agencies; and (ii) ensure user centred rather than biomedical/service-centred models of care. PMID:21619596

Integrating telecare for chronic disease management in the community: what needs to be done?

PubMed

May, Carl R; Finch, Tracy L; Cornford, James; Exley, Catherine; Gately, Claire; Kirk, Sue; Jenkings, K Neil; Osbourne, Janice; Robinson, A Louise; Rogers, Anne; Wilson, Robert; Mair, Frances S

2011-05-27

Telecare could greatly facilitate chronic disease management in the community, but despite government promotion and positive demonstrations its implementation has been limited. This study aimed to identify factors inhibiting the implementation and integration of telecare systems for chronic disease management in the community. Large scale comparative study employing qualitative data collection techniques: semi-structured interviews with key informants, task-groups, and workshops; framework analysis of qualitative data informed by Normalization Process Theory. Drawn from telecare services in community and domestic settings in England and Scotland, 221 participants were included, consisting of health professionals and managers; patients and carers; social care professionals and managers; and service suppliers and manufacturers. Key barriers to telecare integration were uncertainties about coherent and sustainable service and business models; lack of coordination across social and primary care boundaries, lack of financial or other incentives to include telecare within primary care services; a lack of a sense of continuity with previous service provision and self-care work undertaken by patients; and general uncertainty about the adequacy of telecare systems. These problems led to poor integration of policy and practice. Telecare services may offer a cost effective and safe form of care for some people living with chronic illness. Slow and uneven implementation and integration do not stem from problems of adoption. They result from incomplete understanding of the role of telecare systems and subsequent adaption and embeddedness to context, and uncertainties about the best way to develop, coordinate, and sustain services that assist with chronic disease management. Interventions are therefore needed that (i) reduce uncertainty about the ownership of implementation processes and that lock together health and social care agencies; and (ii) ensure user centred rather than biomedical/service-centred models of care.

Primary care nursing activities with patients affected by physical chronic disease and common mental disorders: a qualitative descriptive study.

PubMed

Girard, Ariane; Hudon, Catherine; Poitras, Marie-Eve; Roberge, Pasquale; Chouinard, Maud-Christine

2017-05-01

To describe nursing activities in primary care with patients affected by physical chronic disease and common mental disorders. Patients in primary care who are affected by physical chronic disease and common mental disorders such as anxiety and depression require care and follow-up based on their physical and mental health condition. Primary care nurses are increasingly expected to contribute to the care and follow-up of this growing clientele. However, little is known about the actual activities carried out by primary care nurses in providing this service in the Province of Quebec (Canada). A qualitative descriptive study was conducted. Data were obtained through semistructured individual interviews with 13 nurses practising among patients with physical chronic disease in seven Family Medicine Groups in Quebec (Canada). Participants described five activity domains: assessment of physical and mental health condition, care planning, interprofessional collaboration, therapeutic relationship and health promotion. The full potential of primary care nurses is not always exploited, and some activities could be improved. Evidence for including nurses in collaborative care for patients affected by physical chronic disease and common mental disorders has been shown but is not fully implemented in Family Medicine Groups. Future research should emphasise collaboration among mental health professionals, primary care nurses and family physicians in the care of patients with physical chronic disease and common mental disorders. Primary care nurses would benefit from gaining more knowledge about common mental disorders and from identifying the resources they need to contribute to managing them in an interdisciplinary team. © 2016 John Wiley & Sons Ltd.

Educational Outreach with an Integrated Clinical Tool for Nurse-Led Non-communicable Chronic Disease Management in Primary Care in South Africa: A Pragmatic Cluster Randomised Controlled Trial.

PubMed

Fairall, Lara R; Folb, Naomi; Timmerman, Venessa; Lombard, Carl; Steyn, Krisela; Bachmann, Max O; Bateman, Eric D; Lund, Crick; Cornick, Ruth; Faris, Gill; Gaziano, Thomas; Georgeu-Pepper, Daniella; Zwarenstein, Merrick; Levitt, Naomi S

2016-11-01

In many low-income countries, care for patients with non-communicable diseases (NCDs) and mental health conditions is provided by nurses. The benefits of nurse substitution and supplementation in NCD care in high-income settings are well recognised, but evidence from low- and middle-income countries is limited. Primary Care 101 (PC101) is a programme designed to support and expand nurses' role in NCD care, comprising educational outreach to nurses and a clinical management tool with enhanced prescribing provisions. We evaluated the effect of the programme on primary care nurses' capacity to manage NCDs. In a cluster randomised controlled trial design, 38 public sector primary care clinics in the Western Cape Province, South Africa, were randomised. Nurses in the intervention clinics were trained to use the PC101 management tool during educational outreach sessions delivered by health department trainers and were authorised to prescribe an expanded range of drugs for several NCDs. Control clinics continued use of the Practical Approach to Lung Health and HIV/AIDS in South Africa (PALSA PLUS) management tool and usual training. Patients attending these clinics with one or more of hypertension (3,227), diabetes (1,842), chronic respiratory disease (1,157) or who screened positive for depression (2,466), totalling 4,393 patients, were enrolled between 28 March 2011 and 10 November 2011. Primary outcomes were treatment intensification in the hypertension, diabetes, and chronic respiratory disease cohorts, defined as the proportion of patients in whom treatment was escalated during follow-up over 14 mo, and case detection in the depression cohort. Primary outcome data were analysed for 2,110 (97%) intervention and 2,170 (97%) control group patients. Treatment intensification rates in intervention clinics were not superior to those in the control clinics (hypertension: 44% in the intervention group versus 40% in the control group, risk ratio [RR] 1.08 [95% CI 0.94 to 1.24; p = 0.252]; diabetes: 57% versus 50%, RR 1.10 [0.97 to 1.24; p = 0.126]; chronic respiratory disease: 14% versus 12%, RR 1.08 [0.75 to 1.55; p = 0.674]), nor was case detection of depression (18% versus 24%, RR 0.76 [0.53 to 1.10; p = 0.142]). No adverse effects of the nurses' expanded scope of practice were observed. Limitations of the study include dependence on self-reported diagnoses for inclusion in the patient cohorts, limited data on uptake of PC101 by users, reliance on process outcomes, and insufficient resources to measure important health outcomes, such as HbA1c, at follow-up. Educational outreach to primary care nurses to train them in the use of a management tool involving an expanded role in managing NCDs was feasible and safe but was not associated with treatment intensification or improved case detection for index diseases. This notwithstanding, the intervention, with adjustments to improve its effectiveness, has been adopted for implementation in primary care clinics throughout South Africa. The trial is registered with Current Controlled Trials (ISRCTN20283604).

Educational Outreach with an Integrated Clinical Tool for Nurse-Led Non-communicable Chronic Disease Management in Primary Care in South Africa: A Pragmatic Cluster Randomised Controlled Trial

PubMed Central

Lombard, Carl; Steyn, Krisela; Bachmann, Max O.; Bateman, Eric D.; Lund, Crick; Faris, Gill; Gaziano, Thomas; Georgeu-Pepper, Daniella; Zwarenstein, Merrick; Levitt, Naomi S.

2016-01-01

Background In many low-income countries, care for patients with non-communicable diseases (NCDs) and mental health conditions is provided by nurses. The benefits of nurse substitution and supplementation in NCD care in high-income settings are well recognised, but evidence from low- and middle-income countries is limited. Primary Care 101 (PC101) is a programme designed to support and expand nurses’ role in NCD care, comprising educational outreach to nurses and a clinical management tool with enhanced prescribing provisions. We evaluated the effect of the programme on primary care nurses’ capacity to manage NCDs. Methods and Findings In a cluster randomised controlled trial design, 38 public sector primary care clinics in the Western Cape Province, South Africa, were randomised. Nurses in the intervention clinics were trained to use the PC101 management tool during educational outreach sessions delivered by health department trainers and were authorised to prescribe an expanded range of drugs for several NCDs. Control clinics continued use of the Practical Approach to Lung Health and HIV/AIDS in South Africa (PALSA PLUS) management tool and usual training. Patients attending these clinics with one or more of hypertension (3,227), diabetes (1,842), chronic respiratory disease (1,157) or who screened positive for depression (2,466), totalling 4,393 patients, were enrolled between 28 March 2011 and 10 November 2011. Primary outcomes were treatment intensification in the hypertension, diabetes, and chronic respiratory disease cohorts, defined as the proportion of patients in whom treatment was escalated during follow-up over 14 mo, and case detection in the depression cohort. Primary outcome data were analysed for 2,110 (97%) intervention and 2,170 (97%) control group patients. Treatment intensification rates in intervention clinics were not superior to those in the control clinics (hypertension: 44% in the intervention group versus 40% in the control group, risk ratio [RR] 1.08 [95% CI 0.94 to 1.24; p = 0.252]; diabetes: 57% versus 50%, RR 1.10 [0.97 to 1.24; p = 0.126]; chronic respiratory disease: 14% versus 12%, RR 1.08 [0.75 to 1.55; p = 0.674]), nor was case detection of depression (18% versus 24%, RR 0.76 [0.53 to 1.10; p = 0.142]). No adverse effects of the nurses’ expanded scope of practice were observed. Limitations of the study include dependence on self-reported diagnoses for inclusion in the patient cohorts, limited data on uptake of PC101 by users, reliance on process outcomes, and insufficient resources to measure important health outcomes, such as HbA1c, at follow-up. Conclusions Educational outreach to primary care nurses to train them in the use of a management tool involving an expanded role in managing NCDs was feasible and safe but was not associated with treatment intensification or improved case detection for index diseases. This notwithstanding, the intervention, with adjustments to improve its effectiveness, has been adopted for implementation in primary care clinics throughout South Africa. Trial Registration The trial is registered with Current Controlled Trials (ISRCTN20283604) PMID:27875542

Conserved and variable domains of RNase MRP RNA.

PubMed

Dávila López, Marcela; Rosenblad, Magnus Alm; Samuelsson, Tore

2009-01-01

Ribonuclease MRP is a eukaryotic ribonucleoprotein complex consisting of one RNA molecule and 7-10 protein subunits. One important function of MRP is to catalyze an endonucleolytic cleavage during processing of rRNA precursors. RNase MRP is evolutionary related to RNase P which is critical for tRNA processing. A large number of MRP RNA sequences that now are available have been used to identify conserved primary and secondary structure features of the molecule. MRP RNA has structural features in common with P RNA such as a conserved catalytic core, but it also has unique features and is characterized by a domain highly variable between species. Information regarding primary and secondary structure features is of interest not only in basic studies of the function of MRP RNA, but also because mutations in the RNA give rise to human genetic diseases such as cartilage-hair hypoplasia.

Primary Healthcare-based Diabetes Registry in Puducherry: Design and Methods

PubMed Central

Lakshminarayanan, Subitha; Kar, Sitanshu Sekhar; Gupta, Rajeev; Xavier, Denis; Bhaskar Reddy, S. Vijaya

2017-01-01

Background: Diabetes registries monitor the population prevalence and incidence of diabetes, monitor diabetes control program, provide information of quality of care to health service providers, and provide a sampling frame for interventional studies. This study documents the process of establishing a prospective diabetes registry in a primary health-care setting in Puducherry. Methods: This is a facility-based prospective registry conducted in six randomly selected urban health centers in Puducherry, with enrollment of all known patients with diabetes attending chronic disease clinics. Administrative approvals were obtained from Government Health Services. Manuals for training of medical officers, health-care workers, and case report forms were developed. Diabetes registry was prepared using Epi Info software. Results: In the first phase, demographic characteristics, risk factors, complications, coexisting chronic conditions, lifestyle and medical management, and clinical outcomes were recorded. Around 2177 patients with diabetes have been registered in six Primary Health Centres out of a total of 2948 participants seeking care from chronic disease clinic. Registration coverage ranges from 61% to 105% in these centers. Conclusion: This study has documented methodological details, and learning experiences gained while developing a diabetes registry at the primary health care level and the scope for upscaling to a Management Information System for Diabetes and a State-wide Registry. Improvement in patient care through needs assessment and quality assurance in service delivery is an important theme envisioned by this registry. PMID:28553589

Building health promotion capacity in a primary health care workforce in the Northern Territory: some lessons from practice.

PubMed

Judd, Jenni; Keleher, Helen

2013-12-01

Reorientation of the workforce in primary health care is a complex process and requires specific strategies and interventions. Primary health care providers are a key health care workforce that is expected to deliver tangible outcomes from disease prevention and health promotion strategies. This paper describes a training intervention that occurred as part of a broader participatory action research process for building health promotion capacity in the primary health care workforce. Participatory action research (PAR) was conducted over six action and reflection cycles in a two-year period (2001-02) in an urban community health setting in the Northern Territory. One of the PAR cycles was a training intervention that was identified as a need from a survey in the first action and reflection cycle. This training was facilitated by a health promotion specialist, face-to-face and comprised five 3.5-h sessions over a 5-month period. A pre-post questionnaire was used to measure the knowledge and skills components of the training intervention. The results reinforced the importance of using a participatory approach that involved the primary health care providers themselves. Multiple strategies such as workforce development within capacity building frameworks assisted in shifting work practice more upstream. Additionally, these strategies encouraged more reflective practice and built social capital within the primary health care workforce. Lessons from practice reinforce that workforce development influenced work practice change and is an important element in building the health promotion capacity of primary health care centres. SO WHAT?: Workforce development is critical for reorienting health services. Health promotion specialists play an important role in reorienting practice, which is only effective when combined with other strategies, and driven and led by the primary health care workforce.

Therapeutic possibilities and opportunities for comparative oncopathology.

PubMed

Kaiser, H E

1993-01-01

In reviewing abnormal growth, we may distinguish autonomous and nonautonomous growth processes. The highest diversification is reached in the autonomous non-self-limiting processes, the malignant neoplasms which, if not treated, are characterized by extensive growth and progression. In their development these processes exhibit autonomy on one hand and heterogeneity on the other. Neoplastic and related diseases are extremely complex. It is unacceptable to view them exclusively as genetic or metabolic diseases, or merely as the tumor itself, including its progressive stages, as evidenced in neoplastic metastasis. All these characteristics appear in the different types of neoplastic malignomas, e.g. genetic variations in the neoplastic cells from the normal cells of the parent tissue(s). Included here are tumor progression and cloning of the neoplastic cells, stagewise development of host metabolism and of tumor metabolism; neoplastic hereditary and endocrine-like syndromes as well as paraneoplastic syndromes and cachexia. Neoplastic progression, as observed in the metastatic cascade, derives from the cells of the primary tumor. In contrast, multiple primary tumors originate from different host tissues, whereas the syndromes themselves constitute a symptom complex developing in a neoplasm-bearing host and cannot be assigned to local or distant spread of neoplasms. The only possible explanation for these apparently contrasting processes lies in the interaction of tumor and host metabolism, which seemingly varies in tumor-bearing hosts and in those cases where the tumor has been surgical removed. Antigens and other compounds again show an increase with the usually ensuing secondary tumor spread, a course which provides the basis for most deaths from cancer.

Construction and characterization of 3A-epitope-tagged foot-and-mouth disease virus.

PubMed

Ma, Xueqing; Li, Pinghua; Sun, Pu; Bai, Xingwen; Bao, Huifang; Lu, Zengjun; Fu, Yuanfang; Cao, Yimei; Li, Dong; Chen, Yingli; Qiao, Zilin; Liu, Zaixin

2015-04-01

Nonstructural protein 3A of foot-and-mouth disease virus (FMDV) is a partially conserved protein of 153 amino acids (aa) in most FMDVs examined to date. Specific deletion in the FMDV 3A protein has been associated with the inability of FMDV to grow in primary bovine cells and cause disease in cattle. However, the aa residues playing key roles in these processes are poorly understood. In this study, we constructed epitope-tagged FMDVs containing an 8 aa FLAG epitope, a 9 aa haemagglutinin (HA) epitope, and a 10 aa c-Myc epitope to substitute residues 94-101, 93-101, and 93-102 of 3A protein, respectively, using a recently developed O/SEA/Mya-98 FMDV infectious cDNA clone. Immunofluorescence assay (IFA), Western blot and sequence analysis showed that the epitope-tagged viruses stably maintained and expressed the foreign epitopes even after 10 serial passages in BHK-21 cells. The epitope-tagged viruses displayed growth properties and plaque phenotypes similar to those of the parental virus in BHK-21 cells. However, the epitope-tagged viruses exhibited lower growth rates and smaller plaque size phenotypes than those of the parental virus in primary fetal bovine kidney (FBK) cells, but similar growth properties and plaque phenotypes to those of the recombinant viruses harboring 93-102 deletion in 3A. These results demonstrate that the decreased ability of FMDV to replicate in primary bovine cells was not associated with the length of 3A, and the genetic determinant thought to play key role in decreased ability to replicate in primary bovine cells could be reduced from 93-102 residues to 8 aa residues at positions 94-101 in 3A protein. Copyright © 2015 Elsevier B.V. All rights reserved.

Neuropathology of Alzheimer's disease.

PubMed

Perl, Daniel P

2010-01-01

Alois Alzheimer first pointed out that the disease which would later bear his name has a distinct and recognizable neuropathological substrate. Since then, much has been added to our understanding of the pathological lesions associated with the condition. The 2 primary cardinal lesions associated with Alzheimer's disease are the neurofibrillary tangle and the senile plaque. The neurofibrillary tangle consists of abnormal accumulations of abnormally phosphorylated tau within the perikaryal cytoplasm of certain neurons. The senile plaque consists of a central core of beta-amyloid, a 4-kD peptide, surrounded by abnormally configured neuronal processes or neurites. Other neuropathological lesions are encountered in cases of Alzheimer's disease, but the disease is defined and recognized by these 2 cardinal lesions. Other lesions include poorly understood changes such as granulovacuolar degeneration and eosinophilic rodlike bodies (Hirano bodies). The loss of synaptic components is a change that clearly has a significant impact on cognitive function and represents another important morphological alteration. It is important to recognize that distinguishing between Alzheimer's disease, especially in its early stages, and normal aging may be very difficult, particularly if one is examining the brains of patients who died at an advanced old age. It is also noted that instances of pure forms of Alzheimer's disease, in the absence of other coexistent brain disease processes, such as infarctions or Parkinson's disease-related lesions, are relatively uncommon, and this must be taken into account by researchers who employ postmortem brain tissues for research. (c) 2010 Mount Sinai School of Medicine.

The Surgical Nosology In Primary-care Settings (SNIPS): a simple bridging classification for the interface between primary and specialist care

PubMed Central

Gruen, Russell L; Knox, Stephanie; Britt, Helena; Bailie, Ross S

2004-01-01

Background The interface between primary care and specialist medical services is an important domain for health services research and policy. Of particular concern is optimising specialist services and the organisation of the specialist workforce to meet the needs and demands for specialist care, particularly those generated by referral from primary care. However, differences in the disease classification and reporting of the work of primary and specialist surgical sectors hamper such research. This paper describes the development of a bridging classification for use in the study of potential surgical problems in primary care settings, and for classifying referrals to surgical specialties. Methods A three stage process was undertaken, which involved: (1) defining the categories of surgical disorders from a specialist perspective that were relevant to the specialist-primary care interface; (2) classifying the 'terms' in the International Classification of Primary Care Version 2-Plus (ICPC-2 Plus) to the surgical categories; and (3) using referral data from 303,000 patient encounters in the BEACH study of general practice activity in Australia to define a core set of surgical conditions. Inclusion of terms was based on the probability of specialist referral of patients with such problems, and specialists' perception that they constitute part of normal surgical practice. Results A four-level hierarchy was developed, containing 8, 27 and 79 categories in the first, second and third levels, respectively. These categories classified 2050 ICPC-2 Plus terms that constituted the fourth level, and which covered the spectrum of problems that were managed in primary care and referred to surgical specialists. Conclusion Our method of classifying terms from a primary care classification system to categories delineated by specialists should be applicable to research addressing the interface between primary and specialist care. By describing the process and putting the bridging classification system in the public domain, we invite comment and application in other settings where similar problems might be faced. PMID:15142280

[Epigenetic heredity (deoxyribonucleic acid methylation): Clinical context in neurodegenerative disorders and ATXN2 gene].

PubMed

Laffita-Mesa, José Miguel; Bauer, Peter

2014-10-21

Epigenetics is the group of changes in the phenotype which are related with the process independently of the primary DNA sequence. These changes are intimately related with changes in the gene expression level and its profile across the body. These are mediated by histone tail modifications, DNA methylation, micro-RNAs, with chromatin remodeling remaining as the foundation of epigenetic changes. DNA methylation involves the covalent addition of methyl group to cytosine of the DNA, which is mediated by methyltransferases enzymes. DNA methylation regulates gene expression by repressing transcription, while de-methylation activates gene transcription. Several human diseases are related with the epigenetic process: cancer, Alzheimer disease, stroke, Parkinson disease, and diabetes. We present here the basis of epigenetic inheritance and show the pathogenic mechanisms relating epigenetics in human diseases, specifically with regard to neurodegeneration. We discuss current concepts aimed at understanding the contribution of epigenetics to human neurodegenerative diseases. We also discuss recent findings obtained in our and other centers regarding the ATXN2 gene that causes spinocerebellar ataxia 2 and amyotrophic lateral sclerosis. Epigenetics play a pivotal role in the pathogenesis of human diseases and in several neurodegenerative disorders, and this knowledge will illuminate the pathways in the diagnostic and therapeutic field, which ultimately will be translated into the clinic context of neurodegenerative diseases. Copyright © 2013 Elsevier España, S.L.U. All rights reserved.

Merkel Cell Polyomavirus Exhibits Dominant Control of the Tumor Genome and Transcriptome in Virus-Associated Merkel Cell Carcinoma.

PubMed

Starrett, Gabriel J; Marcelus, Christina; Cantalupo, Paul G; Katz, Joshua P; Cheng, Jingwei; Akagi, Keiko; Thakuria, Manisha; Rabinowits, Guilherme; Wang, Linda C; Symer, David E; Pipas, James M; Harris, Reuben S; DeCaprio, James A

2017-01-03

Merkel cell polyomavirus is the primary etiological agent of the aggressive skin cancer Merkel cell carcinoma (MCC). Recent studies have revealed that UV radiation is the primary mechanism for somatic mutagenesis in nonviral forms of MCC. Here, we analyze the whole transcriptomes and genomes of primary MCC tumors. Our study reveals that virus-associated tumors have minimally altered genomes compared to non-virus-associated tumors, which are dominated by UV-mediated mutations. Although virus-associated tumors contain relatively small mutation burdens, they exhibit a distinct mutation signature with observable transcriptionally biased kataegic events. In addition, viral integration sites overlap focal genome amplifications in virus-associated tumors, suggesting a potential mechanism for these events. Collectively, our studies indicate that Merkel cell polyomavirus is capable of hijacking cellular processes and driving tumorigenesis to the same severity as tens of thousands of somatic genome alterations. A variety of mutagenic processes that shape the evolution of tumors are critical determinants of disease outcome. Here, we sequenced the entire genome of virus-positive and virus-negative primary Merkel cell carcinomas (MCCs), revealing distinct mutation spectra and corresponding expression profiles. Our studies highlight the strong effect that Merkel cell polyomavirus has on the divergent development of viral MCC compared to the somatic alterations that typically drive nonviral tumorigenesis. A more comprehensive understanding of the distinct mutagenic processes operative in viral and nonviral MCCs has implications for the effective treatment of these tumors. Copyright © 2017 Starrett et al.

Clinical features and management of primary sclerosing cholangitis

PubMed Central

Silveira, Marina G; Lindor, Keith D

2008-01-01

Primary sclerosing cholangitis is a chronic cholestatic liver disease characterized by inflammation and fibrosis of the bile ducts, resulting in cirrhosis and need for liver transplantation and reduced life expectancy. The majority of cases occur in young and middle-aged men, often in association with inflammatory bowel disease. The etiology of primary sclerosing cholangitis includes immune-mediated components and elements of undefined nature. No effective medical therapy has been identified. The multiple complications of primary sclerosing cholangitis include metabolic bone disease, dominant strictures, bacterial cholangitis, and malignancy, particularly cholangiocarcinoma, which is the most lethal complication of primary sclerosing cholangitis. Liver transplantation is currently the only life-extending therapeutic alternative for patients with end-stage disease, although recurrence in the allografted liver has been described. A PSC-like variant attracting attention is cholangitis marked by raised levels of the immunoglobulin G4 subclass, prominence of plasma cells within the lesions, and steroid responsiveness. PMID:18528931

Disease-specific clinical pathways - are they feasible in primary care? A mixed-methods study.

PubMed

Grimsmo, Anders; Løhre, Audhild; Røsstad, Tove; Gjerde, Ingunn; Heiberg, Ina; Steinsbekk, Aslak

2018-06-01

To explore the feasibility of disease-specific clinical pathways when used in primary care. A mixed-method sequential exploratory design was used. First, merging and exploring quality interview data across two cases of collaboration between the specialist care and primary care on the introduction of clinical pathways for four selected chronic diseases. Secondly, using quantitative data covering a population of 214,700 to validate and test hypothesis derived from the qualitative findings. Primary care and specialist care collaborating to manage care coordination. Primary-care representatives expressed that their patients often have complex health and social needs that clinical pathways guidelines seldom consider. The representatives experienced that COPD, heart failure, stroke and hip fracture, frequently seen in hospitals, appear in low numbers in primary care. The quantitative study confirmed the extensive complexity among home healthcare nursing patients and demonstrated that, for each of the four selected diagnoses, a homecare nurse on average is responsible for preparing reception of the patient at home after discharge from hospital, less often than every other year. The feasibility of disease-specific pathways in primary care is limited, both from a clinical and organisational perspective, for patients with complex needs. The low prevalence in primary care of patients with important chronic conditions, needing coordinated care after hospital discharge, constricts transferring tasks from specialist care. Generic clinical pathways are likely to be more feasible and efficient for patients in this setting. Key points Clinical pathways in hospitals apply to single-disease guidelines, while more than 90% of the patients discharged to community health care for follow-up have multimorbidity. Primary care has to manage the health care of the patient holistically, with all his or her complex needs. Patients most frequently admitted to hospitals, i.e. patients with COPD, heart failure, stroke and hip fracture are infrequent in primary care and represent a minority among patients in need of coordinated community health care. In primary care, the low rate of receiving patients discharged from hospitals of major chronic diseases hampers maintenance of required specific skills, thus constricting the transfer of tasks to primary care. Generic clinical pathways are suggested to be more feasible than disease-specific pathways for most patients with complex needs.

The utilization of knowledge of and interest in research and development among primary care staff by means of strategic communication - a staff cohort study.

PubMed

Morténius, Helena; Marklund, Bertil; Palm, Lars; Fridlund, Bengt; Baigi, Amir

2012-08-01

The obvious gap between evidence and practice in health care is unfavourable for patient care and requires the promotion of a scientific attitude among health care professionals. The aim of the present study was to determine the utilization of knowledge of and interest in research and development among primary care staff by means of a strategic communication process. A cohort consisting of primary care staff (n = 1276) was designed and strategic communication was utilized as a platform over a 7-year period. Quantitative and qualitative methods were taken in account. We found that 97% of the staff had gained knowledge of research and development, 60% of whom remained interested in the subject. The oral communication channel was the most powerful for creating research interest. Organizational culture was a barrier to interest in science. The study demonstrates a significant increase in knowledge and interest among primary care staff as a result of a strategic communication process. Strategic communication should lead to a more evenly distributed research commitment among all health care professionals, thus facilitating communication between them and patients in order to clarify, for example, the causes of disease. © 2011 Blackwell Publishing Ltd.

Skin diseases in patients with primary psychiatric conditions: a hospital based study.

PubMed

Moftah, Nayera H; Kamel, Abeer M; Attia, Hussein M; El-Baz, Mona Z; Abd El-Moty, Hala M

2013-09-01

Although the relationship between skin diseases in patients with primary psychiatric conditions is important for patient management, studies on this issue are limited. To detect the frequency and type of cutaneous disorders among patients with primary psychiatric conditions. This analytic cross-sectional study was conducted on a total of 400 subjects - 200 patients with primary psychiatric disorders and 200 age and sex matched individuals free from primary psychiatric disorders. Patients included in the study were diagnosed according to The Diagnostic and Statistical Manual of Mental Disorders (DMS IV) Criteria. A specially designed questionnaire including socio-demographic data, medical history, family history and dermatological examination was applied. The data were statistically analyzed. There was a significant statistical increase in the prevalence of skin diseases in general and infectious skin diseases in particular in psychiatric patients compared with non-psychiatric patients (71.5% versus 22%, P<0.001) and (48% versus 11%, P<0.001), respectively. Parasitic infestations (42.7%) were the most common infectious skin diseases in psychiatric patients (P<0.001). Infectious skin diseases in psychiatric patients were seen most in patients diagnosed with schizophrenia (83.6%) and least in obsessive compulsive disorders (30%)(P<0.001). Psychogenic skin disorders were found in 8.4% of psychiatric patients with skin diseases; delusional parasitosis was the most common (50%). Health education of psychiatric patients and/or of their caregiver and periodic monthly inspection of psychiatric patients are highly indicated for the prevention and control of infectious skin diseases in primary psychiatric patients. Copyright © 2013 Ministry of Health, Saudi Arabia. Published by Elsevier Ltd. All rights reserved.

Symptomatic Therapy and Rehabilitation in Primary Progressive Multiple Sclerosis

PubMed Central

Khan, Fary; Amatya, Bhasker; Turner-Stokes, Lynne

2011-01-01

Multiple sclerosis (MS) is an autoimmune inflammatory demyelinating disease of the central nervous system and a major cause of chronic neurological disability in young adults. Primary progressive MS (PPMS) constitutes about 10% of cases, and is characterized by a steady decline in function with no acute attacks. The rate of deterioration from disease onset is more rapid than relapsing remitting and secondary progressive MS types. Multiple system involvement at onset and rapid early progression have a worse prognosis. PPMS can cause significant disability and impact on quality of life. Recent studies are biased in favour of relapsing remitting patients as treatment is now available for them and they are more likely to be seen at MS clinics. Since prognosis for PPMS is worse than other types of MS, the focus of rehabilitation is on managing disability and enhancing participation, and application of a “neuropalliative” approach as the disease progresses. This chapter presents the symptomatic treatment and rehabilitation for persons with MS, including PPMS. A multidisciplinary approach optimizes the intermediate and long-term medical, psychological and social outcomes in this population. Restoration and maintenance of functional independence and societal reintegration, and issues relating to quality of life are addressed in rehabilitation processes. PMID:22013521

Primary Care Physicians' Experience with Disease Management Programs

PubMed Central

Fernandez, Alicia; Grumbach, Kevin; Vranizan, Karen; Osmond, Dennis H; Bindman, Andrew B

2001-01-01

OBJECTIVE To examine primary care physicians' perceptions of how disease management programs affect their practices, their relationships with their patients, and overall patient care. DESIGN Cross-sectional mailed survey. SETTING The 13 largest urban counties in California. PARTICIPANTS General internists, general pediatricians, and family physicians. MEASUREMENTS AND MAIN RESULTS Physicians' self-report of the effects of disease management programs on quality of patient care and their own practices. Respondents included 538 (76%) of 708 physicians: 183 (34%) internists, 199 (38%) family practitioners, and 156 (29%) pediatricians. Disease management programs were available 285 to (53%) physicians; 178 had direct experience with the programs. Three quarters of the 178 physicians believed that disease management programs increased the overall quality of patient care and the quality of care for the targeted disease. Eighty-seven percent continued to provide primary care for their patients in these programs, and 70% reported participating in major patient care decisions. Ninety-one percent reported that the programs had no effect on their income, decreased (38%) or had no effect (48%) on their workload, and increased (48%)) their practice satisfaction. CONCLUSIONS Practicing primary care physicians have generally favorable perceptions of the effect of voluntary, primary care-inclusive, disease management programs on their patients and on their own practice satisfaction. PMID:11318911

Analysis of tumor- and stroma-supplied proteolytic networks reveals a brain metastasis-promoting role for cathepsin S

PubMed Central

Sevenich, Lisa; Bowman, Robert L.; Mason, Steven D.; Quail, Daniela F.; Rapaport, Franck; Elie, Benelita T.; Brogi, Edi; Brastianos, Priscilla K.; Hahn, William C.; Holsinger, Leslie J.; Massagué, Joan; Leslie, Christina S.; Joyce, Johanna A.

2014-01-01

Metastasis remains the most common cause of death in most cancers, with limited therapies for combating disseminated disease. While the primary tumor microenvironment is an important regulator of cancer progression, it is less well understood how different tissue environments influence metastasis. We analyzed tumor-stroma interactions that modulate organ tropism of brain, bone and lung metastasis in xenograft models. We identified a number of potential modulators of site-specific metastasis, including cathepsin S as a regulator of breast-to-brain metastasis. High cathepsin S expression at the primary site correlated with decreased brain metastasis-free survival in breast cancer patients. Both macrophages and tumor cells produce cathepsin S, and only the combined depletion significantly reduced brain metastasis in vivo. Cathepsin S specifically mediates blood-brain barrier transmigration via proteolytic processing of the junctional adhesion molecule (JAM)-B. Pharmacological inhibition of cathepsin S significantly reduced experimental brain metastasis, supporting its consideration as a therapeutic target for this disease. PMID:25086747

Common Standards of Basal Insulin Titration in T2DM

PubMed Central

Arnolds, Sabine; Heise, Tim; Flacke, Frank; Sieber, Jochen

2013-01-01

Type 2 diabetes mellitus has become a worldwide major health problem, and the number of people affected is steadily increasing. Thus, not all patients suffering from the disease can be treated by specialized diabetes centers or outpatient clinics, but by primary care physicians. The latter, however, might have time constraints and have to deal with many kinds of diseases or with multimorbid patients, so their focus is not so much on lowering high blood glucose values. Thus, the physicians, as well as the patients themselves, are often reluctant to initiate and adjust insulin therapy, although basal insulin therapy is considered the appropriate strategy after oral antidiabetic drug failure, according to the latest international guidelines. A substantial number of clinical studies have shown that insulin initiation and optimization can be managed successfully by using titration algorithms—even in cases where patients themselves are the drivers of insulin titration. Nevertheless, tools and strategies are needed to facilitate this process in the daily life of both primary health care professionals and patients with diabetes. PMID:23759411

Metastatic pathways in patients with cutaneous melanoma.

PubMed

Adler, Nikki R; Haydon, Andrew; McLean, Catriona A; Kelly, John W; Mar, Victoria J

2017-01-01

Metastasis represents the end product of an elaborate biological process, which is determined by a complex interplay between metastatic tumour cells, host factors and homoeostatic mechanisms. Cutaneous melanoma can metastasize haematogenously or lymphogenously. The three predominant models that endeavour to explain the patterns of melanoma progression are the stepwise spread model, the simultaneous spread model and the model of differential spread. The time course to the development of metastases differs between the different metastatic routes. There are several clinical and histopathological risk factors for the different metastatic pathways. In particular, patient sex and the anatomical location of the primary tumour influence patterns of disease progression. There is limited existing evidence regarding the relationship between tumour mutation status, other diagnostic and prognostic biomarkers and the metastatic pathways of primary cutaneous melanoma. This knowledge gap needs to be addressed to better identify patients at high risk of disease recurrence and personalize surveillance strategies. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Results of a coordination and shared clinical information programme between primary care and nephrology.

PubMed

García García, Manuel; Valenzuela Mújica, Mari Pau; Martínez Ocaña, Juan Carlos; Otero López, María del Sol; Ponz Clemente, Esther; López Alba, Thaïs; Gálvez Hernández, Enrique

2011-01-01

The high prevalence of chronic kidney disease (CKD) in the general population has created a need to coordinate specialised nephrology care and primary care. Although several systems have been developed to coordinate this process, published results are scarce and contradictory. To present the results of the application of a coordinated programme between nephrology care and primary care through consultations and a system of shared clinical information to facilitate communication and improve the criteria for referring patients. Elaboration of a coordinated care programme by the primary care management team and the nephrology department, based on the SEN-SEMFYC consensus document and a protocol for the study and management of arterial hypertension (AHT). Explanation and implementation in primary health care units. A directory of specialists’ consultations was created, both in-person and via e-mail. A continuous training programme in kidney disease and arterial hypertension was implemented in the in-person consultation sessions. The programme was progressively implemented over a three-year period (2007-2010) in an area of 426,000 inhabitants with 230 general practitioners. Use of a clinical information system named Salut en Xarxa that allows access to clinical reports, diagnoses, prescriptions, test results and clinical progression. Improved referral criteria between primary care and specialised nephrology service. Improved prioritisation of visits. Progressive increase in referrals denied by specialists (28.5% in 2009), accompanied by an explanatory report including suggestions for patient management. Decrease in first nephrology outpatient visits that have been referred from primary care (15% in 2009). Family doctors were generally satisfied with the improvement in communication and the continuous training programme. The main causes for denying referral requests were: patients >70 years with stage 3 CKD (44.15%); patients <70 years with stage 3a CKD (19.15%); albumin/creatinine ratio <500 mg/g (12.23%); non-secondary, non-refractory, essential AHT (11.17%). The general practitioners included in the programme showed great interest and no complaints were registered. The consultations improve adequacy and prioritisation of nephrology visits, allow for better communication between different levels of the health system, and offer systematic training for general practitioners to improve the management of nephrology patients. This process allows for referring nephrology patients with the most complex profiles to nephrology outpatient clinics.

Study of Silymarin and Vitamin E Protective Effects on Silver Nanoparticle Toxicity on Mice Liver Primary Cell Culture.

PubMed

Faedmaleki, Firouz; Shirazi, Farshad H; Ejtemaeimehr, Shahram; Anjarani, Soghra; Salarian, Amir-Ahmad; Ahmadi Ashtiani, Hamidreza; Rastegar, Hossein

2016-02-01

Nanotechnology is a most promising field for generating new applications in medicine, although, only few nano products are currently in use for medical purposes. A most prominent nanoproduct is nanosilver. Nano-silver has biological properties which are significant for consumer products, food technology, textiles, and medical applications (e.g. wound care products, implantable medical devices, in diagnosis, drug delivery, and imaging). For their antibacterial activity, silver nanoparticles (Ag NPs) are largely used in various commercially available products. The use of nano-silver is becoming more and more widespread in medicine and related applications, and due to its increasing exposure, toxicological and environmental issues need to be raised. Cytotoxicity induced by silver nanoparticles (AgNPs) and the role that oxidative stress plays in this process were demonstrated in human hepatoma cells AgNPs agglomerated in the cytoplasm and nuclei of treated cells, and they induced intracellular oxidative stress. AgNP reduced ATP content of the cell and caused damage to mitochondria and increased production of reactive oxygen species (ROS) in a dose-dependent manner. Silymarin was known as a hepatoprotective agent that is used in the treatment of hepatic diseases including viral hepatitis, alcoholic liver diseases, Amanita mushroom poisoning, liver cirrhosis, toxic and drug-induced liver diseases. It promotes protein synthesis, helps in regenerating liver tissue, controls inflammation, enhances glucuronidation, and protects against glutathione depletion. Vitamin E is a well-known antioxidant and has hepatoprotective effect in liver diseases. In this study, we investigated the cytotoxic effects of Ag NPs on primary liver cells of mice. Cell viability (cytotoxicity) was examined with MTT assay after primary liver cells of mice exposure to AgNPs at 1, 10, 50, 100, 150, 200, 400 ppm for 24h. AgNPs caused a concentration- dependent decrease of cell viability (IC50 value = 121.7 ppm or µg/ml). Then the hepatoprotective effect of silymarin and vitamin E were experimented on silver nanoparticle toxicity on mice liver primary cell culture. The results showed that silymarin at 600 µg/ml and vitamin E at 2500 µmol/l have protective effects on silver nanoparticle toxicity on mice liver primary cell culture. Viability percentage of the primary liver cell of the mouse were exposed to silver nanoparticles at 121.7 ppm and co-treatment of silymarin, and vitamin E is more than viability percentage of the primary liver cell of the mouse were exposed to silver nanoparticles and silymarin or silver nanoparticles and vitamin E.

Prospective study of periostitis and finger clubbing in primary biliary cirrhosis and other forms of chronic liver disease.

PubMed Central

Epstein, O; Dick, R; Sherlock, S

1981-01-01

The association of finger clubbing and periostitis has been reported in primary biliary cirrhosis and, more rarely, in other forms of chronic liver disease. The prevalence of periostitis and its relationship to finger clubbing is unknown. In this prospective study, we have determined the prevalence of periostitis and finger clubbing in 74 patients with primary biliary cirrhosis and 54 with other forms of chronic liver disease. Clubbing was present in 24% of patients with primary biliary cirrhosis, 29% with HBsAg negative chronic active hepatitis, and 23% in the group of miscellaneous liver diseases. Symmetrical periostitis affecting the tibiae and fibulae occurred in 35% of patients with primary biliary cirrhosis, 29% with chronic, active hepatitis and 40% of patients in the miscellaneous group. The distal radii and ulnae were affected in only eight patients (6%). In primary biliary cirrhosis, the presence of finger clubbing was strongly associated with periostitis (P less than 0.01), but this association was uncommon in other forms of chronic liver disease. In all forms of chronic liver disease periostitis commonly occurs in the absence of finger clubbing. Marked tenderness over the distal leg bones is a reliable sign of underlying periostitis, but this sign is present in only a third of affected patients. This study indicates that periostitis affecting the lower leg bones is common in patients with chronic liver disease, and its presence should be sought whether or not the patient has finger clubbing. Images Fig. 2 PMID:7227854

Medical and psychological aspects of irritable bowel syndrome.

PubMed

Kim, E C; Dundon, M

1998-01-01

Irritable bowel syndrome is a disease process commonly encountered by primary care providers. Although the cause of this illness is unknown, much is known about the pathophysiology and strong psychosocial influences. Medical practitioners often are aware of the medical aspects of managing irritable bowel syndrome but are not familiar with specific psychologic options. Long-term care of these patients may be aided by collaboration with mental health professionals.

Testing the Adequacy of a Semi-Markov Process

DTIC Science & Technology

2015-09-17

emphasis on covariate detection. 49 VI. BMI Model Analysis According to the Centers of Disease Control and Prevention (CDC) website [24], childhood obesity ...identified an increasing trend over a span of merely four years. Previous studies have drawn correlations between childhood obesity and various childhood and...started in recent years targeting poor dieting and lack of exercise, two of the primary causal factors in childhood obesity according to the CDC

Detection of Glaucoma Using Image Processing Techniques: A Critique.

PubMed

Kumar, B Naveen; Chauhan, R P; Dahiya, Nidhi

2018-01-01

The primary objective of this article is to present a summary of different types of image processing methods employed for the detection of glaucoma, a serious eye disease. Glaucoma affects the optic nerve in which retinal ganglion cells become dead, and this leads to loss of vision. The principal cause is the increase in intraocular pressure, which occurs in open-angle and angle-closure glaucoma, the two major types affecting the optic nerve. In the early stages of glaucoma, no perceptible symptoms appear. As the disease progresses, vision starts to become hazy, leading to blindness. Therefore, early detection of glaucoma is needed for prevention. Manual analysis of ophthalmic images is fairly time-consuming and accuracy depends on the expertise of the professionals. Automatic analysis of retinal images is an important tool. Automation aids in the detection, diagnosis, and prevention of risks associated with the disease. Fundus images obtained from a fundus camera have been used for the analysis. Requisite pre-processing techniques have been applied to the image and, depending upon the technique, various classifiers have been used to detect glaucoma. The techniques mentioned in the present review have certain advantages and disadvantages. Based on this study, one can determine which technique provides an optimum result.

The role of protein crystallography in defining the mechanisms of biogenesis and catalysis in copper amine oxidase.

PubMed

Klema, Valerie J; Wilmot, Carrie M

2012-01-01

Copper amine oxidases (CAOs) are a ubiquitous group of enzymes that catalyze the conversion of primary amines to aldehydes coupled to the reduction of O(2) to H(2)O(2). These enzymes utilize a wide range of substrates from methylamine to polypeptides. Changes in CAO activity are correlated with a variety of human diseases, including diabetes mellitus, Alzheimer's disease, and inflammatory disorders. CAOs contain a cofactor, 2,4,5-trihydroxyphenylalanine quinone (TPQ), that is required for catalytic activity and synthesized through the post-translational modification of a tyrosine residue within the CAO polypeptide. TPQ generation is a self-processing event only requiring the addition of oxygen and Cu(II) to the apoCAO. Thus, the CAO active site supports two very different reactions: TPQ synthesis, and the two electron oxidation of primary amines. Crystal structures are available from bacterial through to human sources, and have given insight into substrate preference, stereospecificity, and structural changes during biogenesis and catalysis. In particular both these processes have been studied in crystallo through the addition of native substrates. These latter studies enable intermediates during physiological turnover to be directly visualized, and demonstrate the power of this relatively recent development in protein crystallography.

Molecular epidemiology: new rules for new tools?

PubMed

Merlo, Domenico Franco; Sormani, Maria Pia; Bruzzi, Paolo

2006-08-30

Molecular epidemiology combines biological markers and epidemiological observations in the study of the environmental and genetic determinants of cancer and other diseases. The potential advantages associated with biomarkers are manifold and include: (a) increased sensitivity and specificity to carcinogenic exposures; (b) more precise evaluation of the interplay between genetic and environmental determinants of cancer; (c) earlier detection of carcinogenic effects of exposure; (d) characterization of disease subtypes-etiologies patterns; (e) evaluation of primary prevention measures. These, in turn, may translate into better tools for etiologic research, individual risk assessment, and, ultimately, primary and secondary prevention. An area that has not received sufficient attention concerns the validation of these biomarkers as surrogate endpoints for cancer risk. Validation of a candidate biomarker's surrogacy is the demonstration that it possesses the properties required for its use as a substitute for a true endpoint. The principles underlying the validation process underwent remarkable developments and discussion in therapeutic research. However, the challenges posed by the application of these principles to epidemiological research, where the basic tool for this validation (i.e., the randomized study) is seldom possible, have not been thoroughly explored. The validation process of surrogacy must be applied rigorously to intermediate biomarkers of cancer risk before using them as risk predictors at the individual as well as at the population level.

The Role of Protein Crystallography in Defining the Mechanisms of Biogenesis and Catalysis in Copper Amine Oxidase

PubMed Central

Klema, Valerie J.; Wilmot, Carrie M.

2012-01-01

Copper amine oxidases (CAOs) are a ubiquitous group of enzymes that catalyze the conversion of primary amines to aldehydes coupled to the reduction of O2 to H2O2. These enzymes utilize a wide range of substrates from methylamine to polypeptides. Changes in CAO activity are correlated with a variety of human diseases, including diabetes mellitus, Alzheimer’s disease, and inflammatory disorders. CAOs contain a cofactor, 2,4,5-trihydroxyphenylalanine quinone (TPQ), that is required for catalytic activity and synthesized through the post-translational modification of a tyrosine residue within the CAO polypeptide. TPQ generation is a self-processing event only requiring the addition of oxygen and Cu(II) to the apoCAO. Thus, the CAO active site supports two very different reactions: TPQ synthesis, and the two electron oxidation of primary amines. Crystal structures are available from bacterial through to human sources, and have given insight into substrate preference, stereospecificity, and structural changes during biogenesis and catalysis. In particular both these processes have been studied in crystallo through the addition of native substrates. These latter studies enable intermediates during physiological turnover to be directly visualized, and demonstrate the power of this relatively recent development in protein crystallography. PMID:22754303

Proteomic and Bioinformatic Profile of Primary Human Oral Epithelial Cells

PubMed Central

Ghosh, Santosh K.; Yohannes, Elizabeth; Bebek, Gurkan; Weinberg, Aaron; Jiang, Bin; Willard, Belinda; Chance, Mark R.; Kinter, Michael T.; McCormick, Thomas S.

2012-01-01

Wounding of the oral mucosa occurs frequently in a highly septic environment. Remarkably, these wounds heal quickly and the oral cavity, for the most part, remains healthy. Deciphering the normal human oral epithelial cell (NHOEC) proteome is critical for understanding the mechanism(s) of protection elicited when the mucosal barrier is intact, as well as when it is breached. Combining 2D gel electrophoresis with shotgun proteomics resulted in identification of 1662 NHOEC proteins. Proteome annotations were performed based on protein classes, molecular functions, disease association and membership in canonical and metabolic signaling pathways. Comparing the NHOEC proteome with a database of innate immunity-relevant interactions (InnateDB) identified 64 common proteins associated with innate immunity. Comparison with published salivary proteomes revealed that 738/1662 NHOEC proteins were common, suggesting that significant numbers of salivary proteins are of epithelial origin. Gene ontology analysis showed similarities in the distributions of NHOEC and saliva proteomes with regard to biological processes, and molecular functions. We also assessed the inter-individual variability of the NHOEC proteome and observed it to be comparable with other primary cells. The baseline proteome described in this study should serve as a resource for proteome studies of the oral mucosa, especially in relation to disease processes. PMID:23035736

Ethics and privacy issues of a practice-based surveillance system: need for a national-level institutional research ethics board and consent standards.

PubMed

Kotecha, Jyoti A; Manca, Donna; Lambert-Lanning, Anita; Keshavjee, Karim; Drummond, Neil; Godwin, Marshall; Greiver, Michelle; Putnam, Wayne; Lussier, Marie-Thérèse; Birtwhistle, Richard

2011-10-01

To describe the challenges the Canadian Primary Care Sentinel Surveillance Network (CPCSSN) experienced with institutional research ethics boards (IREBs) when seeking approvals across jurisdictions and to provide recommendations for overcoming challenges of ethical review for multisite and multijurisdictional surveillance and research. The CPCSSN project collects and validates longitudinal primary care health information (relating to hypertension, diabetes, depression, chronic obstructive lung disease, and osteoarthritis) from electronic medical records across Canada. Privacy and data storage security policies and processes have been developed to protect participants' privacy and confidentiality, and IREB approval is obtained in each participating jurisdiction. Inconsistent interpretation and application of privacy and ethical issues by IREBs delays and impedes research programs that could better inform us about chronic disease. The CPCSSN project's experience with gaining approval from IREBs highlights the difficulty of conducting pan-Canadian health surveillance and multicentre research. Inconsistent IREB approvals to waive explicit individual informed consent produced particular challenges for researchers. The CPCSSN experience highlights the need to develop a better process for researchers to obtain timely and consistent IREB approvals for multicentre surveillance and research. We suggest developing a specialized, national, centralized IREB responsible for approving multisite studies related to population health research.

Primary care closed claims experience of Massachusetts malpractice insurers.

PubMed

Schiff, Gordon D; Puopolo, Ann Louise; Huben-Kearney, Anne; Yu, Winnie; Keohane, Carol; McDonough, Peggy; Ellis, Bonnie R; Bates, David W; Biondolillo, Madeleine

Despite prior focus on high-impact inpatient cases, there are increasing data and awareness that malpractice in the outpatient setting, particularly in primary care, is a leading contributor to malpractice risk and claims. To study patterns of primary care malpractice types, causes, and outcomes as part of a Massachusetts ambulatory malpractice risk and safety improvement project. Retrospective review of pooled closed claims data of 2 malpractice carriers covering most Massachusetts physicians during a 5-year period (January 1, 2005, through December 31, 2009). Data were harmonized between the 2 insurers using a standardized taxonomy. Primary care practices in Massachusetts. All malpractice claims that involved primary care practices insured by the 2 largest insurers in the state were screened. A total of 551 claims from primary care practices were identified for the analysis. Numbers and types of claims, including whether claims involved primary care physicians or practices; classification of alleged malpractice (eg, misdiagnosis or medication error); patient diagnosis; breakdown in care process; and claim outcome (dismissed, settled, verdict for plaintiff, or verdict for defendant). During a 5-year period there were 7224 malpractice claims of which 551 (7.7%) were from primary care practices. Allegations were related to diagnosis in 397 (72.1%), medications in 68 (12.3%), other medical treatment in 41 (7.4%), communication in 15 (2.7%), patient rights in 11 (2.0%), and patient safety or security in 8 (1.5%). Leading diagnoses were cancer (n = 190), heart diseases (n = 43), blood vessel diseases (n = 27), infections (n = 22), and stroke (n = 16). Primary care cases were significantly more likely to be settled (35.2% vs 20.5%) or result in a verdict for the plaintiff (1.6% vs 0.9%) compared with non-general medical malpractice claims (P < .001). In Massachusetts, most primary care claims filed are related to alleged misdiagnosis. Compared with malpractice allegations in other settings, primary care ambulatory claims appear to be more difficult to defend, with more cases settled or resulting in a verdict for the plaintiff.

Molecular pathological epidemiology: new developing frontiers of big data science to study etiologies and pathogenesis.

PubMed

Hamada, Tsuyoshi; Keum, NaNa; Nishihara, Reiko; Ogino, Shuji

2017-03-01

Molecular pathological epidemiology (MPE) is an integrative field that utilizes molecular pathology to incorporate interpersonal heterogeneity of a disease process into epidemiology. In each individual, the development and progression of a disease are determined by a unique combination of exogenous and endogenous factors, resulting in different molecular and pathological subtypes of the disease. Based on "the unique disease principle," the primary aim of MPE is to uncover an interactive relationship between a specific environmental exposure and disease subtypes in determining disease incidence and mortality. This MPE approach can provide etiologic and pathogenic insights, potentially contributing to precision medicine for personalized prevention and treatment. Although breast, prostate, lung, and colorectal cancers have been among the most commonly studied diseases, the MPE approach can be used to study any disease. In addition to molecular features, host immune status and microbiome profile likely affect a disease process, and thus serve as informative biomarkers. As such, further integration of several disciplines into MPE has been achieved (e.g., pharmaco-MPE, immuno-MPE, and microbial MPE), to provide novel insights into underlying etiologic mechanisms. With the advent of high-throughput sequencing technologies, available genomic and epigenomic data have expanded dramatically. The MPE approach can also provide a specific risk estimate for each disease subgroup, thereby enhancing the impact of genome-wide association studies on public health. In this article, we present recent progress of MPE, and discuss the importance of accounting for the disease heterogeneity in the era of big-data health science and precision medicine.

Molecular pathological epidemiology: new developing frontiers of big data science to study etiologies and pathogenesis

PubMed Central

Hamada, Tsuyoshi; Keum, NaNa; Nishihara, Reiko; Ogino, Shuji

2016-01-01

Molecular pathological epidemiology (MPE) is an integrative field that utilizes molecular pathology to incorporate interpersonal heterogeneity of a disease process into epidemiology. In each individual, the development and progression of a disease are determined by a unique combination of exogenous and endogenous factors, resulting in different molecular and pathological subtypes of the disease. Based on “the unique disease principle,” the primary aim of MPE is to uncover an interactive relationship between a specific environmental exposure and disease subtypes in determining disease incidence and mortality. This MPE approach can provide etiologic and pathogenic insights, potentially contributing to precision medicine for personalized prevention and treatment. Although breast, prostate, lung, and colorectal cancers have been among the most commonly studied diseases, the MPE approach can be used to study any disease. In addition to molecular features, host immune status and microbiome profile likely affect a disease process, and thus serve as informative biomarkers. As such, further integration of several disciplines into MPE has been achieved (e.g., pharmaco-MPE, immuno-MPE, and microbial MPE), to provide novel insights into underlying etiologic mechanisms. With the advent of high-throughput sequencing technologies, available genomic and epigenomic data have expanded dramatically. The MPE approach can also provide a specific risk estimate for each disease subgroup, thereby enhancing the impact of genome-wide association studies on public health. In this article, we present recent progress of MPE, and discuss the importance of accounting for the disease heterogeneity in the era of big-data health science and precision medicine. PMID:27738762

Autoimmunity and primary immunodeficiency: two sides of the same coin?

PubMed

Schmidt, Reinhold E; Grimbacher, Bodo; Witte, Torsten

2017-12-19

Autoimmunity and immunodeficiency were previously considered to be mutually exclusive conditions; however, increased understanding of the complex immune regulatory and signalling mechanisms involved, coupled with the application of genetic analysis, is revealing the complex relationships between primary immunodeficiency syndromes and autoimmune diseases. Single-gene defects can cause rare diseases that predominantly present with autoimmune symptoms. Such genetic defects also predispose individuals to recurrent infections (a hallmark of immunodeficiency) and can cause primary immunodeficiencies, which can also lead to immune dysregulation and autoimmunity. Moreover, risk factors for polygenic rheumatic diseases often exist in the same genes as the mutations that give rise to primary immunodeficiency syndromes. In this Review, various primary immunodeficiency syndromes are presented, along with their pathogenetic mechanisms and relationship to autoimmune diseases, in an effort to increase awareness of immunodeficiencies that occur concurrently with autoimmune diseases and to highlight the need to initiate appropriate genetic tests. The growing knowledge of various genetically determined pathologic mechanisms in patients with immunodeficiencies who have autoimmune symptoms opens up new avenues for personalized molecular therapies that could potentially treat immunodeficiency and autoimmunity at the same time, and that could be further explored in the context of autoimmune rheumatic diseases.

Primary anti-phospholipid antibody syndrome causing recurrent venous thrombosis and thrombocytopenia in a patient with Addison's disease.

PubMed

Elebrashy, Ibrahim; Yousief, Elham; Saif, Aasem

2014-12-01

We report a case of Addison's disease presenting with recurrent deep venous thrombosis and thrombocytopenia and proved to have primary anti-phospholipid antibody syndrome. The case report highlights the shared autoimmune nature of both diseases.

Clinicopathological Analysis of Glomerular Disease of Adult Onset Nephrotic Syndrome in an Indian Cohort- A Retrospective Study

PubMed Central

Suryawanshi, Mayur; Karnik, Swapnil

2017-01-01

Introduction Primary glomerular disease presenting with adult onset nephrotic syndrome are a major cause of chronic renal failure worldwide. The spectrum of renal disease presenting with nephrotic syndrome has undergone a gradual change globally over the course of time. However, there still exist regional differences in the incidence of primary glomerular diseases causing adult onset nephrotic syndrome. Aim To observe the spectrum of renal diseases presenting with adult onset nephrotic syndrome with comparative analysis of changing trends over the last five decades with regards to Western and Indian literature. Materials and Methods Subjects included patients with age of 18-80 years presenting with nephrotic syndrome. Renal biopsies with immunofluoroscence studies were performed in all patients. Baseline clinical parameters of serum urea, creatinine, albumin, globulin, cholesterol, 24 hour urine protein and urine microscopy were recorded. Descriptive statistics was used and results were expressed as frequencies, percentages, and mean±standard deviation. Results A total of 227 patients (72% males) were included for the study. Primary glomerular diseases formed 74.01% of total cases and majority of patients included males in the 4th decade. Minimal Change Disease (MCD) (15.8%) including its variants was the most common primary glomerular disease for adult onset of nephrotic syndrome followed by Mesangial proliferative Glomerulonephritis (MSGN) (13.2%). Membranous nephropathy and Type I Membranoproliferative Glomerulonephritis (MPGN) individually accounted for 12.3% of patients. Focal and Segmental Glomerulosclerosis (FSGS) accounted for only 11% of patients. Although, increased incidence of FSGS has been observed worldwide, there exist important regional differences in primary glomerular diseases in Indian population. MCD remains a major glomerular disease for adult onset nephrotic syndrome in different parts of India. Conclusion Our study over three years represents important data of regional variations of primary glomerular diseases presenting with adult onset nephrotic syndrome. PMID:28658768

An anticancer drug suppresses the primary nucleation reaction that initiates the production of the toxic Aβ42 aggregates linked with Alzheimer's disease.

PubMed

Habchi, Johnny; Arosio, Paolo; Perni, Michele; Costa, Ana Rita; Yagi-Utsumi, Maho; Joshi, Priyanka; Chia, Sean; Cohen, Samuel I A; Müller, Martin B D; Linse, Sara; Nollen, Ellen A A; Dobson, Christopher M; Knowles, Tuomas P J; Vendruscolo, Michele

2016-02-01

The conversion of the β-amyloid (Aβ) peptide into pathogenic aggregates is linked to the onset and progression of Alzheimer's disease. Although this observation has prompted an extensive search for therapeutic agents to modulate the concentration of Aβ or inhibit its aggregation, all clinical trials with these objectives have so far failed, at least in part because of a lack of understanding of the molecular mechanisms underlying the process of aggregation and its inhibition. To address this problem, we describe a chemical kinetics approach for rational drug discovery, in which the effects of small molecules on the rates of specific microscopic steps in the self-assembly of Aβ42, the most aggregation-prone variant of Aβ, are analyzed quantitatively. By applying this approach, we report that bexarotene, an anticancer drug approved by the U.S. Food and Drug Administration, selectively targets the primary nucleation step in Aβ42 aggregation, delays the formation of toxic species in neuroblastoma cells, and completely suppresses Aβ42 deposition and its consequences in a Caenorhabditis elegans model of Aβ42-mediated toxicity. These results suggest that the prevention of the primary nucleation of Aβ42 by compounds such as bexarotene could potentially reduce the risk of onset of Alzheimer's disease and, more generally, that our strategy provides a general framework for the rational identification of a range of candidate drugs directed against neurodegenerative disorders.

An anticancer drug suppresses the primary nucleation reaction that initiates the production of the toxic Aβ42 aggregates linked with Alzheimer’s disease

PubMed Central

Habchi, Johnny; Arosio, Paolo; Perni, Michele; Costa, Ana Rita; Yagi-Utsumi, Maho; Joshi, Priyanka; Chia, Sean; Cohen, Samuel I. A.; Müller, Martin B. D.; Linse, Sara; Nollen, Ellen A. A.; Dobson, Christopher M.; Knowles, Tuomas P. J.; Vendruscolo, Michele

2016-01-01

The conversion of the β-amyloid (Aβ) peptide into pathogenic aggregates is linked to the onset and progression of Alzheimer’s disease. Although this observation has prompted an extensive search for therapeutic agents to modulate the concentration of Aβ or inhibit its aggregation, all clinical trials with these objectives have so far failed, at least in part because of a lack of understanding of the molecular mechanisms underlying the process of aggregation and its inhibition. To address this problem, we describe a chemical kinetics approach for rational drug discovery, in which the effects of small molecules on the rates of specific microscopic steps in the self-assembly of Aβ42, the most aggregation-prone variant of Aβ, are analyzed quantitatively. By applying this approach, we report that bexarotene, an anticancer drug approved by the U.S. Food and Drug Administration, selectively targets the primary nucleation step in Aβ42 aggregation, delays the formation of toxic species in neuroblastoma cells, and completely suppresses Aβ42 deposition and its consequences in a Caenorhabditis elegans model of Aβ42-mediated toxicity. These results suggest that the prevention of the primary nucleation of Aβ42 by compounds such as bexarotene could potentially reduce the risk of onset of Alzheimer’s disease and, more generally, that our strategy provides a general framework for the rational identification of a range of candidate drugs directed against neurodegenerative disorders. PMID:26933687

Neuroscience education of undergraduate medical students. Part II: outcome improvement.

PubMed

Resnick, D K; Ramirez, L F

2000-04-01

Because of political and economic pressures, primary care physicians are now charged with greater responsibility for the care of patients with disease processes definitively managed by neurosurgeons. The goal of this study was to establish the feasibility and efficacy of a neurosurgical curriculum designed to teach future primary care physicians about these diseases. A compact, seven-lecture curriculum was developed to teach 3rd-year medical students about degenerative spine disease, stroke, tumor- and hydrocephalus-related raised intracranial pressure, head and spine injury, and subarachnoid hemorrhage. This curriculum was given as part of a 6-week pilot course that included neurology, neurosurgery, ophthalmology, and rehabilitation medicine components. This course was administered to two groups of 18 medical students, and an examination was administered at the end of the pilot course. The same examination was administered to an additional 19 students immediately after their completion of the neurology course currently required. Students enrolled in the pilot neuroscience course performed significantly better (p<0.001) on the examination than those who had completed the standard neurology course. Striking improvements were noted in the recognition and management of head injury, hydrocephalus, and radiculopathy. Inclusion of a short neurosurgery-related curriculum in a combined neuroscience course significantly improved student performance on an examination focusing on the recognition and management of common neurosurgical disorders. Because primary care physicians are responsible for the initial recognition and management of these disorders, the knowledge gained may lead to improved patient care.

Normocalcemic primary hyperparathyroidism

PubMed Central

Bilezikian, John P.; Silverberg, Shonni J.

2011-01-01

SUMMARY Primary hyperparathyroidism is a common disorder of mineral metabolism characterized by incompletely regulated, excessive secretion of parathyroid hormone from one or more of the parathyroid glands. The historical view of this disease describes two distinct entities marked by two eras. When primary hyperparathyroidism was first discovered about 80 years ago, it was always symptomatic with kidney stones, bone disease and marked hypercalcemia. With the advent of the multichannel autoanalyzer about 40 years ago, the clinical phenotype changed to a disorder characterized by mild hypercalcemia and the absence of classical other features of the disease. We may now be entering a 3rd era in the history of this disease in which patients are being discovered with normal total and ionized serum calcium concentrations but with parathyroid hormone levels that are consistently elevated. In this article, we describe this new entity, normocalcemic primary hyperparathyroidism, a forme fruste of the disease. PMID:20485897

Physicians’ perceptions of capacity building for managing chronic disease in seniors using integrated interprofessional care models

PubMed Central

Lee, Linda; Heckman, George; McKelvie, Robert; Jong, Philip; D’Elia, Teresa; Hillier, Loretta M.

2015-01-01

Abstract Objective To explore the barriers to and facilitators of adapting and expanding a primary care memory clinic model to integrate care of additional complex chronic geriatric conditions (heart failure, falls, chronic obstructive pulmonary disease, and frailty) into care processes with the goal of improving outcomes for seniors. Design Mixed-methods study using quantitative (questionnaires) and qualitative (interviews) methods. Setting Ontario. Participants Family physicians currently working in primary care memory clinic teams and supporting geriatric specialists. Methods Family physicians currently working in memory clinic teams (n = 29) and supporting geriatric specialists (n = 9) were recruited as survey participants. Interviews were conducted with memory clinic lead physicians (n = 16). Statistical analysis was done to assess differences between family physician ratings and geriatric specialist ratings related to the capacity for managing complex chronic geriatric conditions, the role of interprofessional collaboration within primary care, and funding and staffing to support geriatric care. Results from both study methods were compared to identify common findings. Main findings Results indicate overall support for expanding the memory clinic model to integrate care for other complex conditions. However, the current primary care structure is challenged to support optimal management of patients with multiple comorbidities, particularly as related to limited funding and staffing resources. Structured training, interprofessional teams, and an active role of geriatric specialists within primary care were identified as important facilitators. Conclusion The memory clinic model, as applied to other complex chronic geriatric conditions, has the potential to build capacity for high-quality primary care, improve health outcomes, promote efficient use of health care resources, and reduce health care costs. PMID:25932482

Using novel methods to examine stress among HIV-positive African American men who have sex with men and women.

PubMed

Glover, Dorie A; Williams, John K; Kisler, Kimberly A

2013-06-01

Biomarker composites (BCs) that objectively quantify psychosocial stress independent of self report could help to identify those at greatest risk for negative health outcomes and elucidate mechanisms of stress-related processes. Here, BCs are examined in the context of existing disease progression among HIV-positive African American men who have sex with men and women (MSMW) with high stress histories, including childhood sexual abuse. Participants (N = 99) collected 12-h overnight and morning urine samples for assay of cortisol and catecholamines (primary BC) and neopterin (an indicator of HIV disease progression). Data on cumulative psychosocial trauma history (severity, types, frequency, age at first incident), posttraumatic stress disorder (PTSD) symptoms, sexual risk behaviors, and a secondary BC consisting of routine health indicators (heart rate, blood pressure, body mass index, waist-to-hip ratio) were also collected. Lifetime trauma exposure was highly pervasive and significantly greater among those meeting a standard cutoff for PTSD caseness (24 %). After controlling for HIV factors (neopterin levels and years with disease), PTSD was a significant (p < .05) predictor of the primary, but not secondary BC. Those with PTSD also had significantly more sexual partners, sex without a condom, and exchange sex for money or drugs than those without PTSD. Specific trauma characteristics predicted PTSD severity and caseness independently and uniquely in regression models (p's < .05-.001). A primary BC appears sensitive to cumulative trauma burden and PTSD in HIV-positive African American MSMW, providing support for the use of BCs to quantify psychosocial stress and inform novel methods for examining mechanisms of stress influenced health behaviors and disease outcomes in at-risk populations.

How do primary care doctors in England and Wales code and manage people with chronic kidney disease? Results from the National Chronic Kidney Disease Audit.

PubMed

Kim, Lois G; Cleary, Faye; Wheeler, David C; Caplin, Ben; Nitsch, Dorothea; Hull, Sally A

2017-10-16

In the UK, primary care records are electronic and require doctors to ascribe disease codes to direct care plans and facilitate safe prescribing. We investigated factors associated with coding of chronic kidney disease (CKD) in patients with reduced kidney function and the impact this has on patient management. We identified patients meeting biochemical criteria for CKD (two estimated glomerular filtration rates <60 mL/min/1.73 m2 taken >90 days apart) from 1039 general practitioner (GP) practices in a UK audit. Clustered logistic regression was used to identify factors associated with coding for CKD and improvement in coding as a result of the audit process. We investigated the relationship between coding and five interventions recommended for CKD: achieving blood pressure targets, proteinuria testing, statin prescription and flu and pneumococcal vaccination. Of 256 000 patients with biochemical CKD, 30% did not have a GP CKD code. Males, older patients, those with more severe CKD, diabetes or hypertension or those prescribed statins were more likely to have a CKD code. Among those with continued biochemical CKD following audit, these same characteristics increased the odds of improved coding. Patients without any kidney diagnosis were less likely to receive optimal care than those coded for CKD [e.g. odds ratio for meeting blood pressure target 0.78 (95% confidence interval 0.76-0.79)]. Older age, male sex, diabetes and hypertension are associated with coding for those with biochemical CKD. CKD coding is associated with receiving key primary care interventions recommended for CKD. Increased efforts to incentivize CKD coding may improve outcomes for CKD patients. © The Author 2017. Published by Oxford University Press on behalf of ERA-EDTA.

Patient and carer experience of obtaining regular prescribed medication for chronic disease in the English National Health Service: a qualitative study

PubMed Central

2013-01-01

Background The increasing burden of chronic disease is recognised globally. Within the English National Health Service, patients with chronic disease comprise of half of all consultations in primary care, and 70% of inpatient bed days. The cost of prescribing long-term medications for those with physical chronic diseases is rising and there is a drive to reduce medicine wastage and costs. While current policies in England are focused on the latter, there has been little previous research on patient experience of ordering and obtaining regular medication for their chronic disease. This paper presents findings from England of a qualitative study and survey of patients and their carers’ experiences of community and primary care based services for physical chronic diseases. Although not the primary focus of the study, the results highlighted particular issues around service delivery of repeat prescriptions. Methods We conducted 21 qualitative in-depth interviews with 30 patients and family carers’ in two Primary Care Trusts in England. Participants were receiving community based care for diabetes, respiratory, neurological or complex co-morbidities, and ranged in age from 39–92 years old. We used a broadly inductive approach to enable themes around patient experience to emerge from the data. Results While the study sought to gain an overview of patient experience, the findings suggested that the processes associated with ordering and obtaining regular medication – the repeat prescription, was most frequently described as a recurring hassle of managing a long-term condition. Issues for patients and carers included multiple journeys to the surgery and pharmacy, lack of synchrony and dissatisfaction with the length of prescriptions. Conclusion Much literature exists around medication waste and cost, which led to encouragement from the NHS in England to reduce dosage units to a 28-day supply. While there has been an acknowledgement that longer supplies may be suitable for people with stable chronic conditions, it appears that there is limited evidence on the impact of shorter length prescriptions on patient and carer experience, adherence and health outcomes. Recent policy documents within England also fail to address possible links between patient experience, adherence and flaws within repeat prescription service delivery. PMID:23705866

Abiotic Versus Biotic Pathogens: Replicative Growth in Host Tissues Key to Discriminating Between Biotoxic Injury and Active Pathogenesis

NASA Technical Reports Server (NTRS)

Schuerger, Andrew C.; Ming, Douglas W.; Golden, D. C.

2012-01-01

Life can be defined as a self-sustaining chemical system capable of undergoing Darwinian evolution; a self-bounded, self-replicating, and self-perpetuating entity [1]. This definition should hold for terrestrial as well as extraterrestrial life-forms. Although, it is reasonable to expect that a Mars life-form would be more adaptable to Mars-like conditions than to Earth-like environments, it remains possible that negative ecological or host interactions might occur if Mars microbiota were to be inadvertently released into the terrestrial environment. A biogenic infectious agent can be defined as a self-sustaining chemical system capable of undergoing Darwinian evolution and derives its sustenance from a living cell or from the by-products of cell death. Disease can be de-fined as the detrimental alteration of one or more ordered metabolic processes in a living host caused by the continued irritation of a primary causal factor or factors; disease is a dynamic process [2]. In contrast, an injury is due to an instantaneous event; injury is not a dynamic process [2]. A causal agent of disease is defined as a pathogen, and can be either abiotic or biotic in nature. Diseases incited by biotic pathogens are the exceptions, not the norms, in terrestrial host-microbe interactions. Disease induction in a plant host can be conceptually characterized using the Disease Triangle (Fig. 1) in which disease occurs only when all host, pathogen, and environ-mental factors that contribute to the development of disease are within conducive ranges for a necessary minimum period of time. For example, plant infection and disease caused by the wheat leaf rust fungus, Puccinia recondita, occur only if virulent spores adhere to genetically susceptible host tissues for at least 4-6 hours under favorable conditions of temperature and moisture [3]. As long as one or more conditions required for disease initiation are not available, disease symptoms will not develop.

Can formal collaborative methodologies improve quality in primary health care in New Zealand? Insights from the EQUIPPED Auckland Collaborative.

PubMed

Palmer, Celia; Bycroft, Janine; Healey, Kate; Field, Adrian; Ghafel, Mazin

2012-12-01

Auckland District Health Board was one of four District Health Boards to trial the Breakthrough Series (BTS) methodology to improve the management of long-term conditions in New Zealand, with support from the Ministry of Health. To improve clinical outcomes, facilitate planned care and promote quality improvement within participating practices in Auckland. Implementation of the Collaborative followed the improvement model / Institute for Healthcare Improvement methodology. Three topic areas were selected: system redesign, cardio-vascular disease/diabetes, and self-management support. An expert advisory group and the Improvement Foundation Australia helped guide project development and implementation. Primary Health Organisation facilitators were trained in the methodology and 15 practice teams participated in the three learning workshops and action periods over 12 months. An independent evaluation study using both quantitative and qualitative methods was conducted. Improvements were recorded in cardiovascular disease risk assessment, practice-level systems of care, self-management systems and follow-up and coordination for patients. Qualitative research found improvements in coordination and teamwork, knowledge of practice populations and understanding of managing long-term conditions. The Collaborative process delivered some real improvements in the systems of care for people with long-term conditions and a change in culture among participating practices. The findings suggest that by strengthening facilitation processes, improving access to comprehensive population audit tools and lengthening the time frame, the process has the potential to make significant improvements in practice. Other organisations should consider this approach when investigating quality improvement programmes.

[Effect of hepatic resection on development of liver metastasis].

PubMed

García-Alonso, I; Palomares, T; Alonso, A; Portugal, V; Castro, B; Caramés, J; Méndez, J

2003-11-01

In the early stages of metastasis, development of the disease is dependent on growth factors produced by the host. There are clinical situations associated with an increase in these factors, such as partial resection of metastasized liver. Given the important role of hepatotrophic factors in liver regeneration, we have studied the effect of partial hepatectomy on the development of residual micrometastases in the liver, and on the neoplastic process as a whole. We used a murine model in which a rabdomiosarcoma was established by subcutaneous inoculation of syngeneic tumor cells in male Wag rats. Subsequently, the primary tumor was resected and/or a 40% hepatectomy was performed. The effect of these two surgical procedures on the tumor process was analyzed on the 25th and 35th days post-inoculation, and the percentage of regenerating hepatocytes was assessed. Both the tumorectomy and liver resection, when not combined, produced an increase in regional adenopathies without modifying the evolution of metastasis in the liver. However, when tumor excision and partial hepatectomy were performed simultaneously, there was a net increase in the metastatic process. In addition to a rapid spread of the disease (lung, mediastinum, retroperitoneum), the number of liver metastases increased by 300%. This development coincided with a steep rise in the percentage of regenerating hepatocytes, which nearly doubled that of the group subjected only to liver resection. We conclude that liver resection, alone or combined with excision of the primary tumor, may enhance tumor progression, both locally and at the metastasic level.

Inflammatory Bowel Disease in Primary Immunodeficiencies.

PubMed

Kelsen, Judith R; Sullivan, Kathleen E

2017-08-01

Inflammatory bowel disease is most often a polygenic disorder with contributions from the intestinal microbiome, defects in barrier function, and dysregulated host responses to microbial stimulation. There is, however, increasing recognition of single gene defects that underlie a subset of patients with inflammatory bowel disease, particularly those with early-onset disease, and this review focuses on the primary immunodeficiencies associated with early-onset inflammatory bowel disease. The advent of next-generation sequencing has led to an improved recognition of single gene defects underlying some cases of inflammatory bowel disease. Among single gene defects, immune response genes are the most frequent category identified. This is also true of common genetic variants associated with inflammatory bowel disease, supporting a pivotal role for host responses in the pathogenesis. This review focuses on practical aspects related to diagnosis and management of children with inflammatory bowel disease who have underlying primary immunodeficiencies.

Treatment of uveal melanoma: where are we now?

PubMed Central

Yang, Jessica; Manson, Daniel K.; Marr, Brian P.; Carvajal, Richard D.

2018-01-01

Uveal melanoma, a rare subset of melanoma, is the most common primary intraocular malignancy in adults. Despite effective primary therapy, nearly 50% of patients will develop metastatic disease. Outcomes for those with metastatic disease remain dismal due to a lack of effective therapies. The unique biology and immunology of uveal melanoma necessitates the development of dedicated management and treatment approaches. Ongoing efforts seek to optimize the efficacy of targeted therapy and immunotherapy in both the adjuvant and metastatic setting. This review provides a comprehensive, updated overview of disease biology and risk stratification, the management of primary disease, options for adjuvant therapy, and the current status of treatment strategies for metastatic disease. PMID:29497459

Asymmetric Distribution of Primary Cilia Allocates Satellite Cells for Self-Renewal.

PubMed

Jaafar Marican, Nur Hayati; Cruz-Migoni, Sara B; Borycki, Anne-Gaëlle

2016-06-14

Regeneration of vertebrate skeletal muscles requires satellite cells, a population of stem cells that are quiescent in normal conditions and divide, differentiate, and self-renew upon activation triggered by exercise, injury, and degenerative diseases. Satellite cell self-renewal is essential for long-term tissue homeostasis, and previous work has identified a number of external cues that control this process. However, little is known of the possible intrinsic control mechanisms of satellite cell self-renewal. Here, we show that quiescent satellite cells harbor a primary cilium, which is rapidly disassembled upon entry into the cell cycle. Contrasting with a commonly accepted belief, cilia reassembly does not occur uniformly in cells exiting the cell cycle. We found that primary cilia reassemble preferentially in cells committed to self-renew, and disruption of cilia reassembly causes a specific deficit in self-renewing satellite cells. These observations indicate that primary cilia provide an intrinsic cue essential for satellite cell self-renewal. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Exercise Promotes Healthy Aging of Skeletal Muscle.

PubMed

Cartee, Gregory D; Hepple, Russell T; Bamman, Marcas M; Zierath, Juleen R

2016-06-14

Primary aging is the progressive and inevitable process of bodily deterioration during adulthood. In skeletal muscle, primary aging causes defective mitochondrial energetics and reduced muscle mass. Secondary aging refers to additional deleterious structural and functional age-related changes caused by diseases and lifestyle factors. Secondary aging can exacerbate deficits in mitochondrial function and muscle mass, concomitant with the development of skeletal muscle insulin resistance. Exercise opposes deleterious effects of secondary aging by preventing the decline in mitochondrial respiration, mitigating aging-related loss of muscle mass and enhancing insulin sensitivity. This review focuses on mechanisms by which exercise promotes "healthy aging" by inducing modifications in skeletal muscle. Copyright © 2016 Elsevier Inc. All rights reserved.

Primary hepatocytes and their cultures in liver apoptosis research

PubMed Central

Vinken, Mathieu; Maes, Michaël; Oliveira, André G.; Cogliati, Bruno; Marques, Pedro E.; Menezes, Gustavo B.; Dagli, Maria Lúcia Zaidan; Vanhaecke, Tamara; Rogiers, Vera

2014-01-01

Apoptosis not only plays a key role in physiological demise of defunct hepatocytes, but is also associated with a plethora of acute and chronic liver diseases as well as with hepatotoxicity. The present paper focuses on the modelling of this mode of programmed cell death in primary hepatocyte cultures. Particular attention is paid to the activation of spontaneous apoptosis during the isolation of hepatocytes from the liver, its progressive manifestation upon the subsequent establishment of cell cultures and simultaneously to strategies to counteract this deleterious process. In addition, currently applied approaches to experimentally induce controlled apoptosis in this in vitro setting for mechanistic research purposes and thereby its detection using relevant biomarkers are reviewed. PMID:24013573

Ultrastructural Characterization of the Glomerulopathy in Alport Mice by Helium Ion Scanning Microscopy (HIM).

PubMed

Tsuji, Kenji; Suleiman, Hani; Miner, Jeffrey H; Daley, James M; Capen, Diane E; Păunescu, Teodor G; Lu, Hua A Jenny

2017-09-15

The glomerulus exercises its filtration barrier function by establishing a complex filtration apparatus consisting of podocyte foot processes, glomerular basement membrane and endothelial cells. Disruption of any component of the glomerular filtration barrier leads to glomerular dysfunction, frequently manifested as proteinuria. Ultrastructural studies of the glomerulus by transmission electron microscopy (TEM) and conventional scanning electron microscopy (SEM) have been routinely used to identify and classify various glomerular diseases. Here we report the application of newly developed helium ion scanning microscopy (HIM) to examine the glomerulopathy in a Col4a3 mutant/Alport syndrome mouse model. Our study revealed unprecedented details of glomerular abnormalities in Col4a3 mutants including distorted podocyte cell bodies and disorganized primary processes. Strikingly, we observed abundant filamentous microprojections arising from podocyte cell bodies and processes, and presence of unique bridging processes that connect the primary processes and foot processes in Alport mice. Furthermore, we detected an altered glomerular endothelium with disrupted sub-endothelial integrity. More importantly, we were able to clearly visualize the complex, three-dimensional podocyte and endothelial interface by HIM. Our study demonstrates that HIM provides nanometer resolution to uncover and rediscover critical ultrastructural characteristics of the glomerulopathy in Col4a3 mutant mice.

Multidisciplinary care planning in the primary care management of completed stroke: a systematic review

PubMed Central

Mitchell, Geoffrey K; Brown, Robyn M; Erikssen, Lars; Tieman, Jennifer J

2008-01-01

Background Chronic disease management requires input from multiple health professionals, both specialist and primary care providers. This study sought to assess the impact of co-ordinated multidisciplinary care in primary care, represented by the delivery of formal care planning by primary care teams or shared across primary-secondary teams, on outcomes in stroke, relative to usual care. Methods A Systematic review of Medline, EMBASE, CINAHL (all 1990–2006), Cochrane Library (Issue 1 2006), and grey literature from web based searching of web sites listed in the CCOHA Health Technology Assessment List Analysis used narrative analysis of findings of randomised and non-randomised trials, and observational and qualitative studies of patients with completed stroke in the primary care setting where care planning was undertaken by 1) a multi-disciplinary primary care team or 2) through shared care by primary and secondary providers. Results One thousand and forty-five citations were retrieved. Eighteen papers were included for analysis. Most care planning took part in the context of multidisciplinary team care based in hospitals with outreach to community patients. Mortality rates are not impacted by multidisciplinary care planning. Functional outcomes of the studies were inconsistent. It is uncertain whether the active engagement of GPs and other primary care professionals in the multidisciplinary care planning contributed to the outcomes in the studies showing a positive effect. There may be process benefits from multidisciplinary care planning that includes primary care professionals and GPs. Few studies actually described the tasks and roles GPs fulfilled and whether this matched what was presumed to be provided. Conclusion While multidisciplinary care planning may not unequivocally improve the care of patients with completed stroke, there may be process benefits such as improved task allocation between providers. Further study on the impact of active GP involvement in multidisciplinary care planning is warranted. PMID:18681977

Characteristics and prognosis of acute myocardial infarction by discharge diagnosis: the REasons for Geographic And Racial Differences in Stroke study

PubMed Central

Levitan, Emily B.; Olubowale, Olusola Top; Gamboa, Christopher M.; Rhodes, J. David; Brown, Todd M.; Muntner, Paul; Deng, Luqin; Safford, Monika M.

2015-01-01

Purpose To compare the characteristics and prognosis of acute myocardial infarctions (AMIs) that were not the primary reason for hospitalization, and thus not primary discharge diagnosis, to AMIs that were the primary reason for hospitalization. Methods Primary discharge diagnoses for REasons for Geographic And Racial Differences in Stroke (REGARDS) participants (black and white men and women age ≥45 years) with adjudicated AMIs were categorized as “AMI” or “other”. Cox models were used to compare mortality up to 5 years post-AMI between primary discharge diagnoses of AMI and other. Results Of 871 AMIs, primary discharge diagnosis was not AMI in 550 (63%). When primary discharge diagnosis was not AMI, average troponin elevations were smaller and heart failure was more common. Adjusted for participant and hospitalization characteristics, all-cause, coronary heart disease, and cardiovascular disease mortality following AMI were similar between groups (hazard ratios, 95% confidence intervals 1.08, 0.80–1.47; 1.29, 0.76–2.18; and 0.86, 0.58–1.27; respectively). Conclusions Studies limited to individuals with primary discharge diagnosis of AMI may underestimate the burden of AMI and exclude a group with elevated risk of all-cause, coronary heart disease, and cardiovascular disease mortality. PMID:25770061

Dissociative semantic breakdown in Alzheimer's disease: evidence from multiple category fluency test.

PubMed

Ting, Simon Kang Seng; Hameed, Shahul; Earnest, Arul; Tan, Eng-King

2013-07-01

Category-specific semantic dissociation particularly in terms of biological and non-biological dichotomy has been described in Alzheimer's disease (AD). We re-examine above finding by performing multiple superordinate category verbal fluency test in AD patients. We analyze the baseline neuropsychological assessment performance of food and animal fluency test of AD patients from a tertiary hospital that collected prospectively over 5 years period and correlation was calculated by Kappa test. The analysis is stratified according to literacy level (primary: 0-6 years education and secondary: >6 years education) and disease severity (MMSE score: mild 19-24, moderate 13-18 and severe <13). A total of 296 AD patients were analyzed and only fair to moderate agreement between food and animal category fluency test was found especially in the mild AD cases (primary: kappa 0.42; secondary: kappa 0.40). Kappa agreement level increases when disease progress especially in the secondary education group. Food category, which is a more relevant semantic knowledge to Singapore population, is generally more affected. Higher educated subjects appeared to have less semantic dissociation effect when disease progress. Despite less primed in daily life, biological category of semantic knowledge appears to be affected less during AD process in highly urbanized Singapore society. Brain appears to have special protective mechanism towards living things. However, education level seems have a modulation effect towards the biological protective mechanism. Copyright © 2012 Elsevier B.V. All rights reserved.

Ethnicity and the diagnosis gap in liver disease: a population-based study.

PubMed

Alazawi, William; Mathur, Rohini; Abeysekera, Kushala; Hull, Sally; Boomla, Kambiz; Robson, John; Foster, Graham R

2014-11-01

Liver disease is a major cause of morbidity and mortality worldwide. Large numbers of liver function tests (LFTs) are performed in primary care, with abnormal liver biochemistry a common finding. Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver injury. Metabolic syndrome, common in people from South Asia, is an important risk factor for NAFLD. It is hypothesised that a large gap exists between numbers of patients with abnormal LFTs and those with recorded liver diagnoses, and that NAFLD is more common among adults of South Asian ethnic groups. A cross-sectional study of 690,683 adults in coterminous general practices in a region with high ethnic diversity. Data were extracted on LFTs, liver disease, and process of care measures from computerised primary care medical records. LFTs were performed on 218,032 patients, of whom 31 627 had elevated serum transaminases. The prevalence of abnormal LFTs was highest among individuals of Bangladeshi ethnicity. Of the patients with abnormal LFTs, 88.4% did not have a coded liver diagnosis. NAFLD was the most frequently recorded liver disease and was most common among Bangladeshi patients. In a multivariate analysis, independent risk factors for NAFLD included Bangladeshi ethnicity, diabetes, raised BMI, hypertension, and hypercholesterolaemia. Abnormal LFTs are common in the population, but are underinvestigated and often remain undiagnosed. Bangladeshi ethnicity is an important independent risk factor for NAFLD. © British Journal of General Practice 2014.

Hair epilation versus surgical excision as primary management of pilonidal disease in the pediatric population

PubMed Central

Bütter, Andreana; Hanson, Melissa; VanHouwelingen, Lisa; Merritt, Neil; Seabrook, Jamie

2015-01-01

Summary Pilonidal disease is a chronic, acquired inflammatory process of the skin due to entrapped hair at the natal cleft. Reported recurrence rates are as high as 30%, and recurrence has been attributed to persistent hair near the surgical site. Although conservative measures, such as meticulous hair control and improved perineal hygiene, have been shown to be effective, these techniques typically require much effort on behalf of the patient. Laser hair epilation (LE) might solve this issue of poor patient compliance while helping patients to avoid surgical excision. In this article, we discuss recurrence rates of pilonidal disease in children treated with LE versus surgical excision in relation to findings from our institution between 2005 and 2013 as well as patient satisfaction with the treatment method. PMID:26011854

Update in Pathological Diagnosis of Orbital Infections and Inflammations

PubMed Central

Lam Choi, Vincent B.; Yuen, Hunter K. L.; Biswas, Jyotirmay; Yanoff, Myron

2011-01-01

Orbital infections and inflammations include a broad spectrum of orbital diseases that can be idiopathic, infectious, from primary or secondary inflammatory processes. Being able to properly diagnose and manage these orbital diseases in a timely manner can avoid permanent vision loss and possibly save a patient's life. When clinicians are faced with such patients, quite often the exact diagnosis cannot be made just based on clinical examination, various laboratory tests and imaging are needed. Moreover, orbital biopsies with histopathological analyses are often required, especially for the atypical cases. Thus, it is important for the clinicians to be familiar with the pathological features and characteristics of these orbital diseases. This review provides a comprehensive update on the clinical and pathological diagnosis of these orbital infections and inflammations. PMID:22224014

The therapeutic use of the relaxation response in stress-related diseases.

PubMed

Esch, Tobias; Fricchione, Gregory L; Stefano, George B

2003-02-01

The objective of this work was to investigate a possible (therapeutic) connection between the relaxation response (RR) and stress-related diseases. Further, common underlying molecular mechanisms and autoregulatory pathways were examined. For the question of (patho)physiology and significance of RR techniques in the treatment of stress-related diseases, we analyzed peer-reviewed references only. The RR has been shown to be an appropriate and relevant therapeutic tool to counteract several stress-related disease processes and certain health-restrictions, particularly in certain immunological, cardiovascular, and neurodegenerative diseases/mental disorders. Further, common underlying molecular mechanisms may exist that represent a connection between the stress response, pathophysiological findings in stress-related diseases, and physiological changes/autoregulatory pathways described in the RR. Here, constitutive or low-output nitric oxide (NO) production may be involved in a protective or ameliorating context, whereas inducible, high-output NO release may facilitate detrimental disease processes. In mild or early disease states, a high degree of biological and physiological flexibility may still be possible (dynamic balance). Here, the therapeutic use of RR techniques may be considered particularly relevant, and the observable (beneficial) effects may be exerted via activation of constitutive NO pathways. RR techniques, regularly part of professional stress management or mind/body medical settings, represent an important tool to be added to therapeutic strategies dealing with stress-related diseases. Moreover, as part of 'healthy' life-style modifications, they may serve primary (or secondary) prevention. Further studies are necessary to elucidate the complex physiology underlying the RR and its impact upon stress-related disease states.

Micrometastases in neuroblastoma: are they clinically important?

PubMed Central

Burchill, S A

2004-01-01

Despite advances in the treatment of neuroblastoma (NBL), recurrence and metastases continue to pose major problems in clinical management. The relation between micrometastases and the development of secondary disease is not fully understood. However, accurate methods to detect low numbers of tumour cells may allow the evaluation of their role in the disease process, and by implication the possible benefits of eliminating them. Although there is substantial evidence for the increased sensitivity of current molecular methods for the detection of NBL cells compared with more conventional cytology, the clinical relevance and usefulness of detecting this disease remain controversial. The primary goal of current translational research must be to evaluate the clinical relevance of micrometastatic disease detected by these methods in multicentre prospective clinical outcome studies. Only then can the clinical usefulness of these methods be defined so that they may be introduced into relevant clinical practice. PMID:14693828

Epigenetic Treatment of Neurodegenerative Ophthalmic Disorders: An Eye Toward the Future

PubMed Central

Moos, Walter H.; Faller, Douglas V.; Glavas, Ioannis P.; Harpp, David N.; Irwin, Michael H.; Kanara, Iphigenia; Pinkert, Carl A.; Powers, Whitney R.; Steliou, Kosta; Vavvas, Demetrios G.; Kodukula, Krishna

2017-01-01

Abstract Eye disease is one of the primary medical conditions that requires attention and therapeutic intervention in ageing populations worldwide. Further, the global burden of diabetes and obesity, along with heart disease, all lead to secondary manifestations of ophthalmic distress. Therefore, there is increased interest in developing innovative new approaches that target various mechanisms and sequelae driving conditions that result in adverse vision. The research challenge is even greater given that the terrain of eye diseases is difficult to landscape into a single therapeutic theme. This report addresses the burden of eye disease due to mitochondrial dysfunction, including antioxidant, autophagic, epigenetic, mitophagic, and other cellular processes that modulate the biomedical end result. In this light, we single out lipoic acid as a potent known natural activator of these pathways, along with alternative and potentially more effective conjugates, which together harness the necessary potency, specificity, and biodistribution parameters required for improved therapeutic outcomes. PMID:29291141

Epigenetic Treatment of Neurodegenerative Ophthalmic Disorders: An Eye Toward the Future.

PubMed

Moos, Walter H; Faller, Douglas V; Glavas, Ioannis P; Harpp, David N; Irwin, Michael H; Kanara, Iphigenia; Pinkert, Carl A; Powers, Whitney R; Steliou, Kosta; Vavvas, Demetrios G; Kodukula, Krishna

2017-01-01

Eye disease is one of the primary medical conditions that requires attention and therapeutic intervention in ageing populations worldwide. Further, the global burden of diabetes and obesity, along with heart disease, all lead to secondary manifestations of ophthalmic distress. Therefore, there is increased interest in developing innovative new approaches that target various mechanisms and sequelae driving conditions that result in adverse vision. The research challenge is even greater given that the terrain of eye diseases is difficult to landscape into a single therapeutic theme. This report addresses the burden of eye disease due to mitochondrial dysfunction, including antioxidant, autophagic, epigenetic, mitophagic, and other cellular processes that modulate the biomedical end result. In this light, we single out lipoic acid as a potent known natural activator of these pathways, along with alternative and potentially more effective conjugates, which together harness the necessary potency, specificity, and biodistribution parameters required for improved therapeutic outcomes.

Towards a Better Understanding of GABAergic Remodeling in Alzheimer’s Disease

PubMed Central

Govindpani, Karan; Calvo-Flores Guzmán, Beatriz; Vinnakota, Chitra; Waldvogel, Henry J.; Kwakowsky, Andrea

2017-01-01

γ-aminobutyric acid (GABA) is the primary inhibitory neurotransmitter in the vertebrate brain. In the past, there has been a major research drive focused on the dysfunction of the glutamatergic and cholinergic neurotransmitter systems in Alzheimer’s disease (AD). However, there is now growing evidence in support of a GABAergic contribution to the pathogenesis of this neurodegenerative disease. Previous studies paint a complex, convoluted and often inconsistent picture of AD-associated GABAergic remodeling. Given the importance of the GABAergic system in neuronal function and homeostasis, in the maintenance of the excitatory/inhibitory balance, and in the processes of learning and memory, such changes in GABAergic function could be an important factor in both early and later stages of AD pathogenesis. Given the limited scope of currently available therapies in modifying the course of the disease, a better understanding of GABAergic remodeling in AD could open up innovative and novel therapeutic opportunities. PMID:28825683

Traumatic brain injury: a risk factor for neurodegenerative diseases.

PubMed

Gupta, Rajaneesh; Sen, Nilkantha

2016-01-01

Traumatic brain injury (TBI), a major global health and socioeconomic problem, is now established as a chronic disease process with a broad spectrum of pathophysiological symptoms followed by long-term disabilities. It triggers multiple and multidirectional biochemical events that lead to neurodegeneration and cognitive impairment. Recent studies have presented strong evidence that patients with TBI history have a tendency to develop proteinopathy, which is the pathophysiological feature of neurodegenerative disorders such as Alzheimer disease (AD), chronic traumatic encephalopathy (CTE), and amyotrophic lateral sclerosis (ALS). This review mainly focuses on mechanisms related to AD, CTE, and ALS that are induced after TBI and their relevance to the advancement of these neurodegenerative diseases. This review encompasses acute effects and chronic neurodegenerative consequences after TBI for a better understanding of TBI-induced neuronal death and to design therapies that will effectively treat patients in the primary or secondary progressive stages.

Amyloid precursor protein and endosomal-lysosomal dysfunction in Alzheimer's disease: inseparable partners in a multifactorial disease.

PubMed

Nixon, Ralph A

2017-07-01

Abnormalities of the endosomal-lysosomal network (ELN) are a signature feature of Alzheimer's disease (AD). These include the earliest known cytopathology that is specific to AD and that affects endosomes and induces the progressive failure of lysosomes, each of which are directly linked by distinct mechanisms to neurodegeneration. The origins of ELN dysfunction and β-amyloidogenesis closely overlap, which reflects their common genetic basis, the established early involvement of endosomes and lysosomes in amyloid precursor protein (APP) processing and clearance, and the pathologic effect of certain APP metabolites on ELN functions. Genes that promote β-amyloidogenesis in AD (APP, PSEN1/2, and APOE4) have primary effects on ELN function. The importance of primary ELN dysfunction to pathogenesis is underscored by the mutations in more than 35 ELN-related genes that, thus far, are known to cause familial neurodegenerative diseases even though different pathogenic proteins may be involved. In this article, I discuss growing evidence that implicates AD gene-driven ELN disruptions as not only the antecedent pathobiology that underlies β-amyloidogenesis but also as the essential partner with APP and its metabolites that drive the development of AD, including tauopathy, synaptic dysfunction, and neurodegeneration. The striking amelioration of diverse deficits in animal AD models by remediating ELN dysfunction further supports a need to integrate APP and ELN relationships, including the role of amyloid-β, into a broader conceptual framework of how AD arises, progresses, and may be effectively therapeutically targeted.-Nixon, R. A. Amyloid precursor protein and endosomal-lysosomal dysfunction in Alzheimer's disease: inseparable partners in a multifactorial disease. © FASEB.

Less aggressive disease in patients with primary squamous cell carcinomas of the thyroid gland and coexisting lymphocytic thyroiditis.

PubMed

Asik, Mehmet; Binnetoglu, Emine; Sen, Hacer; Gunes, Fahri; Muratli, Asli; Kankaya, Duygu; Uysal, Fatma; Sahin, Mustafa; Ukinc, Kubilay

2015-01-01

Primary squamous cell carcinoma (SCC) of the thyroid gland is extremely rare. Infrequently, primary SCC of the thyroid gland is accompanied by other thyroid diseases such as Hashimoto's thyroiditis (HT). Recently, studies have demonstrated that differentiated thyroid cancer with coexisting HT has a better prognosis. However, the prognosis of patients with primary SCC of the thyroid gland and coexistent HT has not been clearly identified. We compared the clinical characteristics and disease stages of patients with primary SCC with and without lymphocytic thyroiditis (LT). We reviewed reports of primary SCC of the thyroid gland published in the English literature. We identified 46 papers that included 17 cases of primary SCC of the thyroid gland with LT and 77 cases of primary SCC of the thyroid gland without LT. Lymph node metastasis and local invasion rates did not differ between these two groups. Distant metastases were absent in patients with LT, and were observed in 13 (16.9%) patients without LT. A greater proportion of patients without LT had advanced stage disease (stage IV A-B-C) than patients with LT (p < 0.05). Patients with primary SCC of the thyroid gland and coexisting LT had lower tumour-node-metastasis stage and frequency of distant metastasis than those without LT. Lymphocytic infiltration in patients with SCC appears to limit tumour growth and distant metastases.

Yeast as a system for modeling mitochondrial disease mechanisms and discovering therapies

PubMed Central

Lasserre, Jean-Paul; Dautant, Alain; Aiyar, Raeka S.; Kucharczyk, Roza; Glatigny, Annie; Tribouillard-Tanvier, Déborah; Rytka, Joanna; Blondel, Marc; Skoczen, Natalia; Reynier, Pascal; Pitayu, Laras; Rötig, Agnès; Delahodde, Agnès; Steinmetz, Lars M.; Dujardin, Geneviève; Procaccio, Vincent; di Rago, Jean-Paul

2015-01-01

ABSTRACT Mitochondrial diseases are severe and largely untreatable. Owing to the many essential processes carried out by mitochondria and the complex cellular systems that support these processes, these diseases are diverse, pleiotropic, and challenging to study. Much of our current understanding of mitochondrial function and dysfunction comes from studies in the baker's yeast Saccharomyces cerevisiae. Because of its good fermenting capacity, S. cerevisiae can survive mutations that inactivate oxidative phosphorylation, has the ability to tolerate the complete loss of mitochondrial DNA (a property referred to as ‘petite-positivity’), and is amenable to mitochondrial and nuclear genome manipulation. These attributes make it an excellent model system for studying and resolving the molecular basis of numerous mitochondrial diseases. Here, we review the invaluable insights this model organism has yielded about diseases caused by mitochondrial dysfunction, which ranges from primary defects in oxidative phosphorylation to metabolic disorders, as well as dysfunctions in maintaining the genome or in the dynamics of mitochondria. Owing to the high level of functional conservation between yeast and human mitochondrial genes, several yeast species have been instrumental in revealing the molecular mechanisms of pathogenic human mitochondrial gene mutations. Importantly, such insights have pointed to potential therapeutic targets, as have genetic and chemical screens using yeast. PMID:26035862

Motor Control Abnormalities in Parkinson’s Disease

PubMed Central

Mazzoni, Pietro; Shabbott, Britne; Cortés, Juan Camilo

2012-01-01

The primary manifestations of Parkinson’s disease are abnormalities of movement, including movement slowness, difficulties with gait and balance, and tremor. We know a considerable amount about the abnormalities of neuronal and muscle activity that correlate with these symptoms. Motor symptoms can also be described in terms of motor control, a level of description that explains how movement variables, such as a limb’s position and speed, are controlled and coordinated. Understanding motor symptoms as motor control abnormalities means to identify how the disease disrupts normal control processes. In the case of Parkinson’s disease, movement slowness, for example, would be explained by a disruption of the control processes that determine normal movement speed. Two long-term benefits of understanding the motor control basis of motor symptoms include the future design of neural prostheses to replace the function of damaged basal ganglia circuits, and the rational design of rehabilitation strategies. This type of understanding, however, remains limited, partly because of limitations in our knowledge of normal motor control. In this article, we review the concept of motor control and describe a few motor symptoms that illustrate the challenges in understanding such symptoms as motor control abnormalities. PMID:22675667

Initial assessment and treatment of refugees in the Mediterranean Sea (a secondary data analysis concerning the initial assessment and treatment of 2656 refugees rescued from distress at sea in support of the EUNAVFOR MED relief mission of the EU).

PubMed

Kulla, M; Josse, F; Stierholz, M; Hossfeld, B; Lampl, L; Helm, M

2016-05-20

As a part of the European Union Naval Force - Mediterranean Operation Sophia (EUNAVFOR Med), the Federal Republic of Germany is contributing to avoid further loss of lives at sea by supplying two naval vessels. In the study presented here we analyse the medical requirements of such rescue missions, as well as the potential benefits of various additional monitoring devices in identifying sick/injured refugees within the primary onboard medical assessment process. Retrospective analysis of the data collected between May - September 2015 from a German Naval Force frigate. Initial data collection focused on the primary medical assessment and treatment process of refugees rescued from distress at sea. Descriptive statistics, uni- and multivariate analysis were performed. The study has received a positive vote from the Ethics Commission of the University of Ulm, Germany (request no. 284/15) and has been registered in the German Register of Clinical Studies (no. DRKS00009535). A total of 2656 refugees had been rescued. 16.9 % of them were classified as "medical treatment required" within the initial onboard medical assessment process. In addition to the clinical assessment by an emergency physician, pulse rate (PR), core body temperature (CBT) and oxygen saturation (SpO2) were evaluated. Sick/injured refugees displayed a statistically significant higher PR (114/min vs. 107/min; p < .001) and CBT (37.1 °C vs. 36.7 °C; p < .001). There was no statistically significant difference in SpO2-values. The same results were found for the subgroup of patients classified as "treatment at emergency hospital required". However, a much larger difference of the mean PR and CBT (35/min resp. 1.8 °C) was found when examining the subgroups of the corresponding refugee boats. A cut-off value of clinical importance could not be found. Predominant diagnoses have been dermatological diseases (55.4), followed by internal diseases (27.7) and trauma (12.1 %). None of the refugees classified as "healthy" within the primary medical assessment process changed to "medical treatment required" during further observation. The initial medical assessment by an emergency physician has proved successful. PR, CBT and SpO2 didn't have any clinical impact to improve the identification of sick/injured refugees within the primary onboard assessment process.

Rivastigmine Lowers Aβ and Increases sAPPα Levels, Which Parallel Elevated Synaptic Markers and Metabolic Activity in Degenerating Primary Rat Neurons

PubMed Central

Bailey, Jason A.; Ray, Balmiki; Greig, Nigel H.; Lahiri, Debomoy K.

2011-01-01

Overproduction of amyloid-β (Aβ) protein in the brain has been hypothesized as the primary toxic insult that, via numerous mechanisms, produces cognitive deficits in Alzheimer's disease (AD). Cholinesterase inhibition is a primary strategy for treatment of AD, and specific compounds of this class have previously been demonstrated to influence Aβ precursor protein (APP) processing and Aβ production. However, little information is available on the effects of rivastigmine, a dual acetylcholinesterase and butyrylcholinesterase inhibitor, on APP processing. As this drug is currently used to treat AD, characterization of its various activities is important to optimize its clinical utility. We have previously shown that rivastigmine can preserve or enhance neuronal and synaptic terminal markers in degenerating primary embryonic cerebrocortical cultures. Given previous reports on the effects of APP and Aβ on synapses, regulation of APP processing represents a plausible mechanism for the synaptic effects of rivastigmine. To test this hypothesis, we treated degenerating primary cultures with rivastigmine and measured secreted APP (sAPP) and Aβ. Rivastigmine treatment increased metabolic activity in these cultured cells, and elevated APP secretion. Analysis of the two major forms of APP secreted by these cultures, attributed to neurons or glia based on molecular weight showed that rivastigmine treatment significantly increased neuronal relative to glial secreted APP. Furthermore, rivastigmine treatment increased α-secretase cleaved sAPPα and decreased Aβ secretion, suggesting a therapeutic mechanism wherein rivastigmine alters the relative activities of the secretase pathways. Assessment of sAPP levels in rodent CSF following once daily rivastigmine administration for 21 days confirmed that elevated levels of APP in cell culture translated in vivo. Taken together, rivastigmine treatment enhances neuronal sAPP and shifts APP processing toward the α-secretase pathway in degenerating neuronal cultures, which mirrors the trend of synaptic proteins, and metabolic activity. PMID:21799757

Review of Amyotrophic Lateral Sclerosis, Parkinson's and Alzheimer's diseases helps further define pathology of the novel paradigm for Alzheimer's with heavy metals as primary disease cause.

PubMed

Cavaleri, Franco

2015-12-01

Pathologies of neurological diseases are increasingly recognized to have common structural and molecular events that can fit, sometimes loosely, into a central pathological theme. A better understanding of the genetic, proteomic and metabolic similarities between three common neurodegenerative diseases - Amyotrophic Lateral Sclerosis (ALS), Parkinson's disease (PD) and Alzheimer's disease (AD) - and how these similarities relate to their unique pathological features may shed more light on the underlying pathology of each. These are complex multigenic neuroinflammatory diseases caused by a combined action by multiple genetic mutations, lifestyle factors and environmental elements including a proposed contribution by transition metals. This comprehensive dynamic makes disease decoding and treatment difficult. One case of ALS, for example, can manifest from a very different pool of genetic mutations than another. In the case of ALS multiple genes in addition to SOD1 are implicated in the pathogenesis of both sporadic and familial variants of the disease. These genes play different roles in the processing and trafficking of signalling, metabolic and structural proteins. However, many of these genetic mutations or the cellular machinery they regulate can play a role in one form or another in PD and AD as well. In addition, the more recent understanding of how TREM-2 mutations factor into inflammatory response has shed new light on how chronic inflammatory activity can escalate to uncontrolled systemic levels in a variety of inflammatory diseases from neurodegenerative, auto-inflammatory and autoimmune diseases. TREM-2 mutations represent yet another complicating element in these multigenic disease pathologies. This review takes us one step back to discuss basic pathological features of these neurodegenerative diseases known to us for some time. However, the objective is to discuss the possibility of related or linked mechanisms that may exist through these basic disease hallmarks that we often classify as absolute signatures of one disease. These new perspectives will be discussed in the context of a new paradigm for Alzheimer's disease that implicates heavy metals as a primary cause. Plausible links between these distinctly different pathologies are presented showing intersections of their distinct pathologies that hinge on metal interactions.

Sleep disorders associated with primary mitochondrial diseases.

PubMed

Ramezani, Ryan J; Stacpoole, Peter W

2014-11-15

Primary mitochondrial diseases are caused by heritable or spontaneous mutations in nuclear DNA or mitochondrial DNA. Such pathological mutations are relatively common in humans and may lead to neurological and neuromuscular complication that could compromise normal sleep behavior. To gain insight into the potential impact of primary mitochondrial disease and sleep pathology, we reviewed the relevant English language literature in which abnormal sleep was reported in association with a mitochondrial disease. We examined publication reported in Web of Science and PubMed from February 1976 through January 2014, and identified 54 patients with a proven or suspected primary mitochondrial disorder who were evaluated for sleep disturbances. Both nuclear DNA and mitochondrial DNA mutations were associated with abnormal sleep patterns. Most subjects who underwent polysomnography had central sleep apnea, and only 5 patients had obstructive sleep apnea. Twenty-four patients showed decreased ventilatory drive in response to hypoxia and/ or hyperapnea that was not considered due to weakness of the intrinsic muscles of respiration. Sleep pathology may be an underreported complication of primary mitochondrial diseases. The probable underlying mechanism is cellular energy failure causing both central neurological and peripheral neuromuscular degenerative changes that commonly present as central sleep apnea and poor ventilatory response to hyperapnea. Increased recognition of the genetics and clinical manifestations of mitochondrial diseases by sleep researchers and clinicians is important in the evaluation and treatment of all patients with sleep disturbances. Prospective population-based studies are required to determine the true prevalence of mitochondrial energy failure in subjects with sleep disorders, and conversely, of individuals with primary mitochondrial diseases and sleep pathology. © 2014 American Academy of Sleep Medicine.

[Clinical integration in the chronic patient].

PubMed

Carretero-Alcántara, Luis; Comes-Górriz, Natividad; Borrás-López, Agustina; Rodríguez-Balo, Alberto; Seara-Aguilar, Germán

2014-01-01

Castilla-La Mancha Health Service is developing the integration of care levels due to the challenge of an aging population in the region. Aging is associated with chronic diseases and an increasing number of concomitant diseases. This poses a major care challenge care, with more fragile patients and new needs. This also requires a sustainable approach: the concurrence of several chronic diseases affects the cost of care, which is especially acute in times of severe economic crisis. One of the pillars of the strategy for dealing with chronic diseases in our region is care integration, in an effort to adapt the organization to the new needs. The Balanced Scorecard or Integrated Scorecard of the integration process was introduced as it has been designed. The integration of primary and hospital care at an organizational level has already been completed, and the development of integrated care processes has also been performed in order to achieve real integration at care level. To help finance this, a prospective capitation system is gradually being implemented, achieving a convergence of per capita costs in the different health areas integrated. Nurses has a key role in this process, their skills as educators and trainers in self-care, in the role of case managers of patients with particularly complex conditions, and the role of professional liaison to improve the transition between care areas and units. Copyright © 2013 Elsevier España, S.L. All rights reserved.

The tumor macroenvironment and systemic regulation of breast cancer progression.

PubMed

Castaño, Zafira; Tracy, Kristin; McAllister, Sandra S

2011-01-01

Breast cancer is the most common malignancy among women worldwide and is the most common cause of death for women between 35 and 50 years of age. Women with breast cancer are at risk of developing metastases for their entire lifetime and, despite local and systemic therapies, approximately 30% of breast cancer patients will relapse (Jemal et al., 2010). Nearly all breast cancer related deaths are due to metastatic disease, even though metastasis is considered to be an inefficient process. In some cases, tumor cells disseminate from primary sites at an early stage, but remain indolent for protracted periods of time before becoming overt, life-threatening tumors. Little is known about the mechanisms that cause these indolent tumors to grow into malignant disease. Because of this gap in our understanding, we are unable to predict which breast cancer patients are likely to experience disease relapse or develop metastases years after treatment of their primary tumor. A better understanding of the mechanisms and signals involved in the exit of tumor cells from dormancy would not only allow for more accurate selection of patients that would benefit from systemic therapy, but could also lead to the development of more targeted therapies to inhibit the signals that promote disease progression. In this review, we address the systemic, or "macroenvironmental", contribution to tumor initiation and progression and what is known about how a pro-tumorigenic systemic environment is established.

Autoantibody Signaling in Pemphigus Vulgaris: Development of an Integrated Model

PubMed Central

Sajda, Thomas; Sinha, Animesh A.

2018-01-01

Pemphigus vulgaris (PV) is an autoimmune skin blistering disease effecting both cutaneous and mucosal epithelia. Blister formation in PV is known to result from the binding of autoantibodies (autoAbs) to keratinocyte antigens. The primary antigenic targets of pathogenic autoAbs are known to be desmoglein 3, and to a lesser extent, desmoglein 1, cadherin family proteins that partially comprise the desmosome, a protein structure responsible for maintaining cell adhesion, although additional autoAbs, whose role in blister formation is still unclear, are also known to be present in PV patients. Nevertheless, there remain large gaps in knowledge concerning the precise mechanisms through which autoAb binding induces blister formation. Consequently, the primary therapeutic interventions for PV focus on systemic immunosuppression, whose side effects represent a significant health risk to patients. In an effort to identify novel, disease-specific therapeutic targets, a multitude of studies attempting to elucidate the pathogenic mechanisms downstream of autoAb binding, have led to significant advancements in the understanding of autoAb-mediated blister formation. Despite this enhanced characterization of disease processes, a satisfactory explanation of autoAb-induced acantholysis still does not exist. Here, we carefully review the literature investigating the pathogenic disease mechanisms in PV and, taking into account the full scope of results from these studies, provide a novel, comprehensive theory of blister formation in PV. PMID:29755451

Predictors of primary care referrals to a vascular disease prevention lifestyle program among participants in a cluster randomised trial.

PubMed

Passey, Megan E; Laws, Rachel A; Jayasinghe, Upali W; Fanaian, Mahnaz; McKenzie, Suzanne; Powell-Davies, Gawaine; Lyle, David; Harris, Mark F

2012-08-03

Cardiovascular disease accounts for a large burden of disease, but is amenable to prevention through lifestyle modification. This paper examines patient and practice predictors of referral to a lifestyle modification program (LMP) offered as part of a cluster randomised controlled trial (RCT) of prevention of vascular disease in primary care. Data from the intervention arm of a cluster RCT which recruited 36 practices through two rural and three urban primary care organisations were used. In each practice, 160 eligible high risk patients were invited to participate. Practices were randomly allocated to intervention or control groups. Intervention practice staff were trained in screening, motivational interviewing and counselling and encouraged to refer high risk patients to a LMP involving individual and group sessions. Data include patient surveys; clinical audit; practice survey on capacity for preventive care; referral records from the LMP. Predictors of referral were examined using multi-level logistic regression modelling after adjustment for confounding factors. Of 301 eligible patients, 190 (63.1%) were referred to the LMP. Independent predictors of referral were baseline BMI ≥ 25 (OR 2.87 95%CI:1.10, 7.47), physical inactivity (OR 2.90 95%CI:1.36,6.14), contemplation/preparation/action stage of change for physical activity (OR 2.75 95%CI:1.07, 7.03), rural location (OR 12.50 95%CI:1.43, 109.7) and smaller practice size (1-3 GPs) (OR 16.05 95%CI:2.74, 94.24). Providing a well-structured evidence-based lifestyle intervention, free of charge to patients, with coordination and support for referral processes resulted in over 60% of participating high risk patients being referred for disease prevention. Contrary to expectations, referrals were more frequent from rural and smaller practices suggesting that these practices may be more ready to engage with these programs. ACTRN12607000423415.

Characteristics of renal papillae in kidney stone formers.

PubMed

Marien, Tracy P; Miller, Nicole L

2016-12-01

The mechanism of kidney stone formation is not well understood. In order to better understand the pathophysiology for specific kidney stone compositions and systemic diseases associated with kidney stones, endoscopic papillary mapping studies with concurrent biopsies have been conducted. This review will summarize the findings of these studies and proposed mechanisms for thirteen disease processes associated with kidney stones. A review of the literature was performed identifying thirteen studies that endoscopically mapped and biopsied renal papillae of different stone formers. These studies characterized renal papillae based on amount of Randall's plaque, Bellini's duct pathology, papillary contour changes, presence of attached stones, pitting, and frequently papillary and cortical biopsies. The groups studied and reviewed here are kidney stone formers who have a history of idiopathic calcium oxalate stone formation, cystinuria, brushite stones, gastric bypass, ileostomy, small bowel resection, primary hyperparathyroidism, distal renal tubular acidosis (dRTA), primary hyperoxaluria, idiopathic calcium phosphate stone formation, medullary sponge kidney (MSK), uric acid stones, and struvite stones. A proposed standardized scoring system for papillary pathology was also reviewed. The series showed various degrees and types of changes to the renal papillae and corresponding histopathologic changes for each type of stone former reviewed. Those with predominantly alone Randall's plaque pathology had less tissue damage versus those with extensive Bellini's duct lesions who had more interstitial fibrosis and cortical pathology. Randall's plaques are associated with stone formers who have low urinary volume, high urinary calcium, and acidic urine and thus are frequently seen in those with brushite stones, primary hyperparathyroidism, small bowel resection, and idiopathic calcium phosphate stone formers. Bellini's duct plugging and pathology is theorized to occur via free solution crystallization, ductal obstruction, inflammation, cellular injury, fibrosis, and acidification defects. Ureteroscopic manifestations of stone disease can vary from normal appearing papillae to significantly diseased appearing papillae. Some diseases have very characteristic papillary changes. Further studies are necessary to fully elucidate the mechanisms of stone formation in patients with nephrolithiasis.

Human leukocyte antigens as a risk factor for the primary diseases leading to end stage renal disease in Egyptian patients.

PubMed

El-Gezawy, Ebtesam M; Baset, Hesham A Abdel; Nasif, Khalid A; Osama, Amany; AbdelAzeem, Hanan G; Ali, Medhat; Khalil, Rasha Y

2011-01-01

The number of patients with end stage renal disease (ESRD) is increasing considerably worldwide. The incidence of ESRD is likely to be higher than that reported from the developed world, with diabetic nephropathy, hypertension and chronic glomerulonephritis being the most common causes in Egypt. The aim of the present study is to investigate the Human leukocyte antigens [HLA-A,-B and -DRB1 antigens] as a risk factor for the primary diseases leading to ESRD in Egyptian patients. Our study included a total of 457 individuals comprising 207 ESRD patients and 250 healthy controls were enrolled into the study. Class I [HLA-A and-B] typing was performed by complement-dependent cytotoxicity (CDC) method, while class II HLA-DRB1 typing was performed by low resolution polymerase chain reaction (PCR)-sequence-specific oligonucleotide probe [PCR-SSOP]. We found that the most common primary disease groups leading to ESRD classified as Diabetic nephropathy, hypertensive nephrosclerosis and chronic glomerulonephritis. HLA-A2, -B8 and DRB1*3 and HLA-DRB1*11 significantly correlated with diabetic nephropathy, respectively. B8-DR3 haplotype is susceptible to DM. In, conclusion, determination of HLA-A,-B and -DRB1 as a risk factor for primary diseases leading to ESRD might be beneficial in preventing progression to ESRD and recurrence of the primary disease post-transplantation.

Endo-Perio Dilemma: A Brief Review

PubMed Central

Singh, Preetinder

2011-01-01

The actual relationship between periodontal and pulpal disease was first described by Simring and Goldberg in 1964. Since then, the term “perio-endo” lesion has been used to describe lesions due to inflammatory products found in varying degrees in both the periodontium and the pulpal tissues. The pulp and periodontium have embryonic, anatomic and functional inter-relationships. The simultaneous existence of pulpal problems and inflammatory periodontal disease can complicate diagnosis and treatment planning. A perio-endo lesion can have a varied pathogenesis which ranges from quite simple to relatively complex one. Knowledge of these disease processes is essential in coming to the correct diagnosis. This is achievable by careful history taking, examination and the use of special tests. The prognosis and treatment of each endodontic-periodontal disease type varies. Primary periodontal disease with secondary endodontic involvement and true combined endodontic-periodontal diseases require both endodontic and periodontal therapies. The prognosis of these cases depends on the severity of periodontal disease and the response to periodontal treatment. This enables the operator to construct a suitable treatment plan where unnecessary, prolonged or even detrimental treatment is avoided. PMID:22132014

Endo-perio dilemma: a brief review.

PubMed

Singh, Preetinder

2011-01-01

The actual relationship between periodontal and pulpal disease was first described by Simring and Goldberg in 1964. Since then, the term "perio-endo" lesion has been used to describe lesions due to inflammatory products found in varying degrees in both the periodontium and the pulpal tissues. The pulp and periodontium have embryonic, anatomic and functional inter-relationships. The simultaneous existence of pulpal problems and inflammatory periodontal disease can complicate diagnosis and treatment planning. A perio-endo lesion can have a varied pathogenesis which ranges from quite simple to relatively complex one. Knowledge of these disease processes is essential in coming to the correct diagnosis. This is achievable by careful history taking, examination and the use of special tests. The prognosis and treatment of each endodontic-periodontal disease type varies. Primary periodontal disease with secondary endodontic involvement and true combined endodontic-periodontal diseases require both endodontic and periodontal therapies. The prognosis of these cases depends on the severity of periodontal disease and the response to periodontal treatment. This enables the operator to construct a suitable treatment plan where unnecessary, prolonged or even detrimental treatment is avoided.

[Limb lymphedema as a first manifestation of primary intestinal lymphangiectasia (Waldmann's disease)].

PubMed

Boursier, V; Vignes, S

2004-05-01

Primary intestinal lymphangiectasia (Waldmann's disease) is characterized by protein-losing enteropathy occurring more frequently in childhood. Chronic diarrhea and diffuse edema are the main clinical manifestations. Peripheral lymphedema may also be associated. Lymphedema is usually present at the time of diagnosis or appears later in the course of the disease. We report the observation of a 31-year-old man suffering from an upper, lower limb and genital lymphedema many years before diagnosis of primary intestinal lymphangiectasia was established. Lower limb lymphoscintigraphy confirmed lymphedema and duodenal biopsies lymphangiectasia. Hypoproteinemia, lymphopenia and hypogammaglobulinemia were also noted. Treatment of lymphedema included low stretch bandaging and elastic stocking. No dietary management with a low-fat diet was added. Search for primary intestinal lymphangiectasia with biological parameters would be useful when primary lymphedema is present. Especially since primary intestinal lymphangiectasia may be complicated by occurrence of B cell lymphoma.

Developing primary care in Hong Kong: evidence into practice and the development of reference frameworks.

PubMed

Griffiths, Sian M; Lee, Jeff P M

2012-10-01

Enhancing primary care is one of the proposals put forward in the Healthcare Reform Consultation Document "Your Health, Your Life" issued in March 2008. In 2009, the Working Group on Primary Care, chaired by the Secretary for Food and Health, recommended the development of age-group and disease-specific primary care conceptual models and reference frameworks. Drawing on international experience and best evidence, the Task Force on Conceptual Model and Preventive Protocols of the Working Group on Primary Care has developed two reference frameworks for the management of two common chronic diseases in Hong Kong, namely diabetes and hypertension, in primary care settings. Adopting a population approach for the prevention and control of diabetes and hypertension across the life course, the reference frameworks aim to provide evidence-based and appropriate recommendations for the provision of continuing and comprehensive care for patients with chronic diseases in the community.

Using electronic health record alerts to provide public health situational awareness to clinicians.

PubMed

Lurio, Joseph; Morrison, Frances P; Pichardo, Michelle; Berg, Rachel; Buck, Michael D; Wu, Winfred; Kitson, Kwame; Mostashari, Farzad; Calman, Neil

2010-01-01

Alerting providers to public health situations requires timeliness and context-relevance, both lacking in current systems. Incorporating decision support tools into electronic health records may provide a way to deploy public health alerts to clinicians at the point of care. A timely process for responding to Health Alert Network messages sent by the New York City Department of Health and Mental Hygiene was developed by a network of community health centers. Alerts with order sets and recommended actions were created to notify primary care providers of local disease outbreaks. The process, effect, and lessons learned from alerts for Legionella, toxogenic E coli, and measles outbreaks are described. Electronic alerts have the potential to improve management of diseases during an outbreak, including appropriate laboratory testing, management guidance, and diagnostic assistance as well as to enhance bi-directional data exchange between clinical and public health organizations.

Using electronic health record alerts to provide public health situational awareness to clinicians

PubMed Central

Lurio, Joseph; Pichardo, Michelle; Berg, Rachel; Buck, Michael D; Wu, Winfred; Kitson, Kwame; Mostashari, Farzad; Calman, Neil

2010-01-01

Alerting providers to public health situations requires timeliness and context-relevance, both lacking in current systems. Incorporating decision support tools into electronic health records may provide a way to deploy public health alerts to clinicians at the point of care. A timely process for responding to Health Alert Network messages sent by the New York City Department of Health and Mental Hygiene was developed by a network of community health centers. Alerts with order sets and recommended actions were created to notify primary care providers of local disease outbreaks. The process, effect, and lessons learned from alerts for Legionella, toxogenic E coli, and measles outbreaks are described. Electronic alerts have the potential to improve management of diseases during an outbreak, including appropriate laboratory testing, management guidance, and diagnostic assistance as well as to enhance bi-directional data exchange between clinical and public health organizations. PMID:20190067

28 CFR 79.21 - Definitions.

Code of Federal Regulations, 2010 CFR

2010-07-01

... lymphocytic leukemia, multiple myeloma, lymphomas, Hodgkin's disease, primary cancer of the thyroid, primary cancer of the male breast, primary cancer of the female breast, primary cancer of the esophagus, primary cancer of the stomach, primary cancer of the pharynx, primary cancer of the small intestine, primary...

28 CFR 79.21 - Definitions.

Code of Federal Regulations, 2011 CFR

2011-07-01

... lymphocytic leukemia, multiple myeloma, lymphomas, Hodgkin's disease, primary cancer of the thyroid, primary cancer of the male breast, primary cancer of the female breast, primary cancer of the esophagus, primary cancer of the stomach, primary cancer of the pharynx, primary cancer of the small intestine, primary...

28 CFR 79.21 - Definitions.

Code of Federal Regulations, 2012 CFR

2012-07-01

... lymphocytic leukemia, multiple myeloma, lymphomas, Hodgkin's disease, primary cancer of the thyroid, primary cancer of the male breast, primary cancer of the female breast, primary cancer of the esophagus, primary cancer of the stomach, primary cancer of the pharynx, primary cancer of the small intestine, primary...

28 CFR 79.21 - Definitions.

Code of Federal Regulations, 2013 CFR

2013-07-01

... lymphocytic leukemia, multiple myeloma, lymphomas, Hodgkin's disease, primary cancer of the thyroid, primary cancer of the male breast, primary cancer of the female breast, primary cancer of the esophagus, primary cancer of the stomach, primary cancer of the pharynx, primary cancer of the small intestine, primary...

28 CFR 79.21 - Definitions.

Code of Federal Regulations, 2014 CFR

2014-07-01

... lymphocytic leukemia, multiple myeloma, lymphomas, Hodgkin's disease, primary cancer of the thyroid, primary cancer of the male breast, primary cancer of the female breast, primary cancer of the esophagus, primary cancer of the stomach, primary cancer of the pharynx, primary cancer of the small intestine, primary...

Super-enhancer-mediated RNA processing revealed by integrative microRNA network analysis

PubMed Central

Suzuki, Hiroshi I.; Young, Richard A; Sharp, Phillip A

2017-01-01

Summary Super-enhancers are an emerging sub-class of regulatory regions controlling cell identity and disease genes. However, their biological function and impact on miRNA networks are unclear. Here we report that super-enhancers drive the biogenesis of master miRNAs crucial for cell identity by enhancing both transcription and Drosha/DGCR8-mediated primary miRNA (pri-miRNA) processing. Super-enhancers, together with broad H3K4me3 domains, shape a tissue-specific and evolutionarily conserved atlas of miRNA expression and function. CRISPR/Cas9 genomics revealed that super-enhancer constituents act cooperatively and facilitate Drosha/DGCR8 recruitment and pri-miRNA processing to boost cell-specific miRNA production. The BET-bromodomain inhibitor JQ1 preferentially inhibits super-enhancer-directed cotranscriptional pri-miRNA processing. Furthermore, super-enhancers are characterized by pervasive interaction with DGCR8/Drosha and DGCR8/Drosha-regulated mRNA stability control, suggesting unique RNA regulation at super-enhancers. Finally, super-enhancers mark multiple miRNAs associated with cancer hallmarks. This study presents principles underlying miRNA biology in health and disease and a unrecognized higher-order property of super-enhancers in RNA processing beyond transcription. PMID:28283057

Use of electronic clinical reminders to increase preventive screenings in a primary care setting: blueprint from a successful process in Kodiak, Alaska.

PubMed

Onders, Robert; Spillane, James; Reilley, Brigg; Leston, Jessica

2014-01-01

The Kodiak Area Native Association (KANA) provides primary health care in Kodiak, Alaska and 6 outlying villages. KANA sought to actively improve key preventive screening rates for its patients. KANA adopted an electronic health record in 2008 and deployed national clinical reminders from the Indian Health Service for 5 key preventive screenings: tobacco use, alcohol use, depression, intimate partner violence, and a comprehensive cardiovascular exam. Clinical reminders were deployed in a 5-step process: (a) establish clinical demand, (b) pilot test reminder, (c) expand reminder to all providers, (d) measure outcomes and share results, and (e) delegate clinical reminder follow-up (primarily to nurses). Data from 2007-2011 show screening rates for all 5 measures improved considerably, to levels significantly above the national average for Indian Health Service facilities. Clinical reminders have been a key part of a multistep process to improve screening for depression, tobacco cessation, intimate partner violence, alcohol use, and cardiovascular disease. If deployed correctly, reminders are valuable tools in identifying patients who are overdue for preventive health screenings.

Factors predicting the duration of adrenal insufficiency in patients successfully treated for Cushing disease and nonmalignant primary adrenal Cushing syndrome.

PubMed

Prete, Alessandro; Paragliola, Rosa Maria; Bottiglieri, Filomena; Rota, Carlo Antonio; Pontecorvi, Alfredo; Salvatori, Roberto; Corsello, Salvatore Maria

2017-03-01

Successful treatment of Cushing syndrome causes transient or permanent adrenal insufficiency deriving from endogenous hypercortisolism-induced hypothalamus-pituitary-adrenal-axis suppression. We analyzed pre-treatment factors potentially affecting the duration of adrenal insufficiency. We conducted a retrospective analysis on patients successfully treated for Cushing disease (15 patients) who underwent transsphenoidal surgery, and nonmalignant primary adrenal Cushing syndrome (31 patients) who underwent unilateral adrenalectomy, divided into patients with overt primary adrenal Cushing syndrome (14 patients) and subclinical primary adrenal Cushing syndrome (17 patients). Epidemiological data, medical history, and hormonal parameters depending on the etiology of hypercortisolism were collected and compared to the duration of adrenal insufficiency. The median duration of follow-up after surgery for Cushing disease and primary adrenal Cushing syndrome was 70 and 48 months, respectively. In the Cushing disease group, the median duration of adrenal insufficiency after transsphenoidal surgery was 15 months: younger age at diagnosis and longer duration of signs and symptoms of hypercortisolism before diagnosis and surgery were associated with longer duration of adrenal insufficiency. The median duration of adrenal insufficiency was 6 months for subclinical primary adrenal Cushing syndrome and 18.5 months for overt primary adrenal Cushing syndrome. The biochemical severity of hypercortisolism, the grade of hypothalamus-pituitary-adrenal-axis suppression, and treatment with ketoconazole before surgery accounted for longer duration of adrenal insufficiency. In patients with Cushing disease, younger age and delayed diagnosis and treatment predict longer need for glucocorticoid replacement therapy after successful transsphenoidal surgery. In patients with primary adrenal Cushing syndrome, the severity of hypercortisolism plays a primary role in influencing the duration of adrenal insufficiency after unilateral adrenalectomy.

T cell-B cell interactions in primary immunodeficiencies.

PubMed

Tangye, Stuart G; Deenick, Elissa K; Palendira, Umaimainthan; Ma, Cindy S

2012-02-01

Regulated interactions between cells of the immune system facilitate the generation of successful immune responses, thereby enabling efficient neutralization and clearance of pathogens and the establishment of both cell- and humoral-mediated immunological memory. The corollary of this is that impediments to efficient cell-cell interactions, normally necessary for differentiation and effector functions of immune cells, underly the clinical features and disease pathogenesis of primary immunodeficiencies. In affected individuals, these defects manifest as impaired long-term humoral immunity and susceptibility to infection by specific pathogens. In this review, we discuss the importance of, and requirements for, effective interactions between B cells and T cells during the formation of CD4(+) T follicular helper cells and the elicitation of cytotoxic function of virus-specific CD8(+) T cells, as well as how these processes are abrogated in primary immunodeficiencies due to loss-of-function mutations in defined genes. © 2012 New York Academy of Sciences.

Benefit from autologous stem cell transplantation in primary refractory myeloma? Different outcomes in progressive versus stable disease

PubMed Central

Rosiñol, Laura; García-Sanz, Ramón; Lahuerta, Juan José; Hernández-García, Miguel; Granell, Miquel; de la Rubia, Javier; Oriol, Albert; Hernández-Ruiz, Belén; Rayón, Consuelo; Navarro, Isabel; García-Ruiz, Juan Carlos; Besalduch, Joan; Gardella, Santiago; Jiménez, Javier López; Díaz-Mediavilla, Joaquín; Alegre, Adrián; Miguel, Jesús San; Bladé, Joan

2012-01-01

Background Several studies of autologous stem cell transplantation in primary refractory myeloma have produced encouraging results. However, the outcome of primary refractory patients with stable disease has not been analyzed separately from the outcome of patients with progressive disease. Design and Methods In the Spanish Myeloma Group 2000 trial, 80 patients with primary refractory myeloma (49 with stable disease and 31 with progressive disease), i.e. who were refractory to initial chemotherapy, were scheduled for tandem transplants (double autologous transplant or a single autologous transplant followed by an allogeneic transplant). Patients with primary refractory disease included those who never achieved a minimal response (≥25% M-protein decrease) or better. Responses were assessed using the European Bone Marrow Transplant criteria. Results There were no significant differences in the rates of partial response or better between patients with stable or progressive disease. However, 38% of the patients with stable disease at the time of transplantation remained in a stable condition or achieved a minimal response after transplantation versus 7% in the group with progressive disease (P=0.0017) and the rate of early progression after transplantation was significantly higher among the group with progressive disease at the time of transplantation (22% versus 2%; P=0.0043). After a median follow-up of 6.6 years, the median survival after first transplant of the whole series was 2.3 years. Progression-free and overall survival from the first transplant were shorter in patients with progressive disease (0.6 versus 2.3 years, P=0.00004 and 1.1 versus 6 years, P=0.00002, respectively). Conclusions Our results show that patients with progressive refractory myeloma do not benefit from autologous transplantation, while patients with stable disease have an outcome comparable to those with chemosensitive disease. (ClinicalTrials.gov:NCT00560053) PMID:22058223

Non-communicable diseases in low- and middle-income countries: context, determinants and health policy

PubMed Central

Miranda, J. J.; Kinra, S.; Casas, J. P.; Smith, G. Davey; Ebrahim, S.

2009-01-01

Summary The rise of non-communicable diseases and their impact in low- and middle-income countries has gained increased attention in recent years. However, the explanation for this rise is mostly an extrapolation from the history of high-income countries whose experience differed from the development processes affecting today’s low- and middle-income countries. This review appraises these differences in context to gain a better understanding of the epidemic of non-communicable diseases in low- and middle-income countries. Theories of developmental and degenerative determinants of non-communicable diseases are discussed to provide strong evidence for a causally informed approach to prevention. Health policies for non-communicable diseases are considered in terms of interventions to reduce population risk and individual susceptibility and the research needs for low- and middle-income countries are discussed. Finally, the need for health system reform to strengthen primary care is highlighted as a major policy to reduce the toll of this rising epidemic. PMID:18937743

Recovery of Renibacterium salmoninarum from naturally infected salmonine stocks in Michigan using a modified culture protocol

USGS Publications Warehouse

Faisal, M.; Eissa, A.E.; Starliper, C.E.

2010-01-01

Renibacterium salmoninarum, the causative agent of bacterial kidney disease (BKD), is a fastidious and slow-growing bacterium that is extremely difficult to grow in vitro. Herein, we describe a modified primary culture protocol that encompasses a modified bacteriological culture medium and a tissue processing procedure. In order to facilitate the release of R. salmoninarum from granulomatous tissues, kidneys of infected fish were homogenized in a high speed stomacher. The kidney disease medium (KDM2), routinely used for primary culture of R. salmoninarum was modified by the addition of antibiotics and metabolites. When a relatively large inoculum of diluted kidney homogenate was streak-plate inoculated onto the modified KDM2, colonial growth of R. salmoninarum was achieved within 5-7. days, compared to the standard of two weeks or more. The modified procedure was then used to determine the prevalence of R. salmoninarum among representative captive and feral salmonid stocks in Michigan. Prevalence and clinical manifestations varied among species, strains of fish, and locations; however, R. salmoninarum isolates were biochemically homogenous. The improved primary culture procedure described in this study enabled selective and quick isolation of R. salmoninarum. Also, the isolates retrieved in this study constitute a unique biological resource for future studies of R. salmoninarum in the Laurentian Great Lakes. ?? 2009 University of Cairo.

28 CFR 79.50 - Scope of subpart.

Code of Federal Regulations, 2010 CFR

2010-07-01

... “millers” who contracted primary lung cancer, one of a limited number of nonmalignant respiratory diseases, primary renal cancer, or chronic renal disease, following employment for at least one year as a uranium...

28 CFR 79.52 - Criteria for eligibility for claims by uranium millers.

Code of Federal Regulations, 2010 CFR

2010-07-01

..., 1942, and ending on December 31, 1971; and (c) The claimant contracted primary lung cancer, a nonmalignant respiratory disease, primary renal cancer, or chronic renal disease (including nephritis and...

28 CFR 79.50 - Scope of subpart.

Code of Federal Regulations, 2011 CFR

2011-07-01

... “millers” who contracted primary lung cancer, one of a limited number of nonmalignant respiratory diseases, primary renal cancer, or chronic renal disease, following employment for at least one year as a uranium...

28 CFR 79.52 - Criteria for eligibility for claims by uranium millers.

Code of Federal Regulations, 2011 CFR

2011-07-01

..., 1942, and ending on December 31, 1971; and (c) The claimant contracted primary lung cancer, a nonmalignant respiratory disease, primary renal cancer, or chronic renal disease (including nephritis and...

28 CFR 79.52 - Criteria for eligibility for claims by uranium millers.

Code of Federal Regulations, 2014 CFR

2014-07-01

..., 1942, and ending on December 31, 1971; and (c) The claimant contracted primary lung cancer, a nonmalignant respiratory disease, primary renal cancer, or chronic renal disease (including nephritis and...

28 CFR 79.52 - Criteria for eligibility for claims by uranium millers.

Code of Federal Regulations, 2012 CFR

2012-07-01

..., 1942, and ending on December 31, 1971; and (c) The claimant contracted primary lung cancer, a nonmalignant respiratory disease, primary renal cancer, or chronic renal disease (including nephritis and...

28 CFR 79.50 - Scope of subpart.

Code of Federal Regulations, 2014 CFR

2014-07-01

... “millers” who contracted primary lung cancer, one of a limited number of nonmalignant respiratory diseases, primary renal cancer, or chronic renal disease, following employment for at least one year as a uranium...

28 CFR 79.52 - Criteria for eligibility for claims by uranium millers.

Code of Federal Regulations, 2013 CFR

2013-07-01

..., 1942, and ending on December 31, 1971; and (c) The claimant contracted primary lung cancer, a nonmalignant respiratory disease, primary renal cancer, or chronic renal disease (including nephritis and...

28 CFR 79.50 - Scope of subpart.

Code of Federal Regulations, 2012 CFR

2012-07-01

... “millers” who contracted primary lung cancer, one of a limited number of nonmalignant respiratory diseases, primary renal cancer, or chronic renal disease, following employment for at least one year as a uranium...

28 CFR 79.50 - Scope of subpart.

Code of Federal Regulations, 2013 CFR

2013-07-01

... “millers” who contracted primary lung cancer, one of a limited number of nonmalignant respiratory diseases, primary renal cancer, or chronic renal disease, following employment for at least one year as a uranium...

Primary Health Care Providers' Knowledge Gaps on Parkinson's Disease

ERIC Educational Resources Information Center

Thompson, Megan R.; Stone, Ramona F.; Ochs, V. Dan; Litvan, Irene

2013-01-01

In order to determine primary health care providers' (PCPs) knowledge gaps on Parkinson's disease, data were collected before and after a one-hour continuing medical education (CME) lecture on early Parkinson's disease recognition and treatment from a sample of 104 PCPs participating at an annual meeting. The main outcome measure was the…

Diagnosis and Treatment of Gastrointestinal Disorders in Patients With Primary Immunodeficiency

PubMed Central

AGARWAL, SHRADHA; MAYER, LLOYD

2013-01-01

Gastrointestinal disorders such as chronic or acute diarrhea, malabsorption, abdominal pain, and inflammatory bowel diseases can indicate immune deficiency. The gastrointestinal tract is the largest lymphoid organ in the body, so it is not surprising that intestinal diseases are common among immunodeficient patients. Gastroenterologists therefore must be able to diagnose and treat patients with primary immunodeficiency. Immune-related gastrointestinal diseases can be classified as those that develop primarily via autoimmunity, infection, an inflammatory response, or malignancy. Immunodeficient and immunocompetent patients with gastrointestinal diseases present with similar symptoms. However, intestinal biopsy specimens from immunodeficient patients often have distinct histologic features, and these patients often fail to respond to conventional therapies. Therefore, early recognition of symptoms and referral to an immunologist for a basic immune evaluation is required to select appropriate treatments. Therapies for primary immunodeficiency comprise immunoglobulin replacement, antibiotics, and, in severe cases, bone marrow transplantation. Treatment of immunodeficient patients with concomitant gastrointestinal disease can be challenging, and therapy with immunomodulators often is required for severe disease. This review aims to guide gastroenterologists in the diagnosis and treatment of patients with primary immunodeficiency. PMID:23501398

The Ariadne principles: how to handle multimorbidity in primary care consultations.

PubMed

Muth, Christiane; van den Akker, Marjan; Blom, Jeanet W; Mallen, Christian D; Rochon, Justine; Schellevis, François G; Becker, Annette; Beyer, Martin; Gensichen, Jochen; Kirchner, Hanna; Perera, Rafael; Prados-Torres, Alexandra; Scherer, Martin; Thiem, Ulrich; van den Bussche, Hendrik; Glasziou, Paul P

2014-12-08

Multimorbidity is a health issue mostly dealt with in primary care practice. As a result of their generalist and patient-centered approach, long-lasting relationships with patients, and responsibility for continuity and coordination of care, family physicians are particularly well placed to manage patients with multimorbidity. However, conflicts arising from the application of multiple disease oriented guidelines and the burden of diseases and treatments often make consultations challenging. To provide orientation in decision making in multimorbidity during primary care consultations, we developed guiding principles and named them after the Greek mythological figure Ariadne. For this purpose, we convened a two-day expert workshop accompanied by an international symposium in October 2012 in Frankfurt, Germany. Against the background of the current state of knowledge presented and discussed at the symposium, 19 experts from North America, Europe, and Australia identified the key issues of concern in the management of multimorbidity in primary care in panel and small group sessions and agreed upon making use of formal and informal consensus methods. The proposed preliminary principles were refined during a multistage feedback process and discussed using a case example. The sharing of realistic treatment goals by physicians and patients is at the core of the Ariadne principles. These result from i) a thorough interaction assessment of the patient's conditions, treatments, constitution, and context; ii) the prioritization of health problems that take into account the patient's preferences - his or her most and least desired outcomes; and iii) individualized management realizes the best options of care in diagnostics, treatment, and prevention to achieve the goals. Goal attainment is followed-up in accordance with a re-assessment in planned visits. The occurrence of new or changed conditions, such as an increase in severity, or a changed context may trigger the (re-)start of the process. Further work is needed on the implementation of the formulated principles, but they were recognized and appreciated as important by family physicians and primary care researchers.Please see related article: http://www.biomedcentral.com/1741-7015/12/222.

Improving Care for Patients With or at Risk for Chronic Kidney Disease Using Electronic Medical Record Interventions: A Pragmatic Cluster-Randomized Trial Protocol

PubMed Central

Nash, Danielle M.; Ivers, Noah M.; Young, Jacqueline; Jaakkimainen, R. Liisa; Garg, Amit X.; Tu, Karen

2017-01-01

Background: Many patients with or at risk for chronic kidney disease (CKD) in the primary care setting are not receiving recommended care. Objective: The objective of this study is to determine whether a multifaceted, low-cost intervention compared with usual care improves the care of patients with or at risk for CKD in the primary care setting. Design: A pragmatic cluster-randomized trial, with an embedded qualitative process evaluation, will be conducted. Setting: The study population comes from the Electronic Medical Record Administrative data Linked Database®, which includes clinical data for more than 140 000 rostered adults cared for by 194 family physicians in 34 clinics across Ontario, Canada. The 34 primary care clinics will be randomized to the intervention or control group. Intervention: The intervention group will receive resources from the “CKD toolkit” to help improve care including practice audit and feedback, printed educational materials for physicians and patients, electronic decision support and reminders, and implementation support. Measurements: Patients with or at risk for CKD within participating clinics will be identified using laboratory data in the electronic medical records. Outcomes will be assessed after dissemination of the CKD tools and after 2 rounds of feedback on performance on quality indicators have been sent to the physicians using information from the electronic medical records. The primary outcome is the proportion of patients aged 50 to 80 years with nondialysis-dependent CKD who are on a statin. Secondary outcomes include process of care measures such as screening tests, CKD recognition, monitoring tests, angiotensin-converting enzyme inhibitor or angiotensin receptor blocker prescriptions, blood pressure targets met, and nephrologist referral. Hierarchical analytic modeling will be performed to account for clustering. Semistructured interviews will be conducted with a random purposeful sample of physicians in the intervention group to understand why the intervention achieved the observed effects. Conclusions: If our intervention improves care, then the CKD toolkit can be adapted and scaled for use in other primary care clinics which use electronic medical records. Trial Registration: ClinicalTrials.gov Identifier: NCT02274298 PMID:28607686

A nurse-facilitated depression screening program in an Army primary care clinic: an evidence-based project.

PubMed

Yackel, Edward E; McKennan, Madelyn S; Fox-Deise, Adrianna

2010-01-01

Depression, sometimes with suicidal manifestations, is a medical condition commonly seen in primary care clinics. Routine screening for depression and suicidal ideation is recommended of all adult patients in the primary care setting because it offers depressed patients a greater chance of recovery and response to treatment, yet such screening often is overlooked or omitted. The purpose of this study was to develop, to implement, and to test the efficacy of a systematic depression screening process to increase the identification of depression in family members of active duty soldiers older than 18 years at a military family practice clinic located on an Army infantry post in the Pacific. The Iowa Model of Evidence-Based Practice to Promote Quality Care was used to develop a practice guideline incorporating a decision algorithm for nurses to screen for depression. A pilot project to institute this change in practice was conducted, and outcomes were measured. Before implementation, approximately 100 patients were diagnosed with depression in each of the 3 months preceding the practice change. Approximately 130 patients a month were assigned a 311.0 Code 3 months after the practice change, and 140 patients per month received screenings and were assigned the correct International Classification of Diseases, Ninth Revision Code 311.0 at 1 year. The improved screening and coding for depression and suicidality added approximately 3 minutes to the patient screening process. The education of staff in the process of screening for depression and correct coding coupled with monitoring and staff feedback improved compliance with the identification and the documentation of patients with depression. Nurses were more likely than primary care providers to agree strongly that screening for depression enhances quality of care. Data gathered during this project support the integration of military and civilian nurse-facilitated screening for depression in the military primary care setting. The decision algorithm should be adapted and tested in other primary care environments.

The relationship between organizational climate and quality of chronic disease management.

PubMed

Benzer, Justin K; Young, Gary; Stolzmann, Kelly; Osatuke, Katerine; Meterko, Mark; Caso, Allison; White, Bert; Mohr, David C

2011-06-01

To test the utility of a two-dimensional model of organizational climate for explaining variation in diabetes care between primary care clinics. Secondary data were obtained from 223 primary care clinics in the Department of Veterans Affairs health care system. Organizational climate was defined using the dimensions of task and relational climate. The association between primary care organizational climate and diabetes processes and intermediate outcomes were estimated for 4,539 patients in a cross-sectional study. All data were collected from administrative datasets. The climate data were drawn from the 2007 VA All Employee Survey, and the outcomes data were collected as part of the VA External Peer Review Program. Climate data were aggregated to the facility level of analysis and merged with patient-level data. Relational climate was related to an increased likelihood of diabetes care process adherence, with significant but small effects for adherence to intermediate outcomes. Task climate was generally not shown to be related to adherence. The role of relational climate in predicting the quality of chronic care was supported. Future research should examine the mediators and moderators of relational climate and further investigate task climate. © Health Research and Educational Trust.

The increasing burden of potentially preventable liver disease among adult liver transplant recipients: A comparative analysis of liver transplant indication by era in Australia and New Zealand.

PubMed

Howell, Jessica; Balderson, Glenda; Hellard, Margaret; Gow, Paul; Strasser, Simone; Stuart, Katherine; Wigg, Alan; Jeffrey, Gary; Gane, Ed; Angus, Peter W

2016-02-01

Hepatitis C (HCV), hepatitis B (HBV), alcohol-related liver disease (ALD), and non-alcohol-related fatty liver disease (NAFLD) are leading indications for adult liver transplantation in Australia and New Zealand. However, these diseases are potentially preventable through effective primary and/or secondary prevention strategies. This study evaluates the relative contribution of potentially preventable liver diseases to liver transplant numbers in Australia and New Zealand over time. Prospectively recorded clinical, demographic, and outcome data were collected from the Australian and New Zealand Liver Transplant Registry for all primary adult liver transplants performed in Australia and New Zealand from 1 January 1985 until 31 December 2012. Potentially preventable liver disease was defined as HBV, HCV, NAFLD, ALD, and HCC. The etiology of liver disease leading to liver transplantation and the proportion of preventable liver disease-related liver transplantation was compared between Era 1 (1985-1993), Era 2 (1994-2003), and Era 3 (2004-2012). Overall, 1252 of 3266 adult primary liver transplants (38.3%) were performed for potentially preventable liver disease. There was a significant increase in the proportion of liver transplants because of preventable liver disease from 21.2% (93 of 439) in Era 1, to 49.8% (623 of 1252) in Era 2 and 63.5% (1000 of 1575) in Era 3 (P < 0.0001). Over time, there was a significant increase in HCV (P < 0.0001), ALD (P = 0.002), and NAFLD (P < 0.0001) as a primary indication for adult liver transplant, whereas HBV has significantly decreased from Era 1 to Era 3 as an indication for transplant (P < 0.0001). The number of transplants performed for HCC also increased across Eras (P < 0.0001), with 84% due to underlying potentially preventable liver disease. Since 2004, the majority of primary adult liver transplants within Australia and New Zealand have been because of potentially preventable liver diseases and the prevalence of these diseases has increased over time. This finding represents an opportunity for clinicians to make a significant impact on the overall burden of advanced liver disease in Australia and New Zealand by improving primary and secondary prevention measures. © 2015 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

Contemporary Approach to the Diagnosis and Management of Primary Angle-Closure Disease.

PubMed

Razeghinejad, M Reza; Myers, Jonathan S

2018-05-16

Primary angle closure disease spectrum varies from a narrow angle to advanced glaucoma. A variety of imaging technologies may assist the clinician in determining the pathophysiology and diagnosis of primary angle closure, but gonioscopy remains a mainstay of clinical evaluation. Laser iridotomy effectively eliminates the pupillary block component of angle closure; however, studies show that in many patients the iridocorneal angle remains narrow from underlying anatomic issues, and increasing lens size often leads to further narrowing over time. Recent studies have further characterized the role of the lens in angle closure disease, and cataract or clear lens extraction is increasingly used earlier in its management. As a first surgical step in angle closure glaucoma, lens extraction alone often effectively controls the pressure with less risk of complications than concurrent or stand alone glaucoma surgery, but may not be sufficient in more advanced or severe disease. We provide a comprehensive review on the primary angle-closure disease nomenclature, imaging, and current laser and surgical management. Copyright © 2018. Published by Elsevier Inc.

Bayesian inference for an emerging arboreal epidemic in the presence of control

PubMed Central

Parry, Matthew; Gibson, Gavin J.; Parnell, Stephen; Gottwald, Tim R.; Irey, Michael S.; Gast, Timothy C.; Gilligan, Christopher A.

2014-01-01

The spread of Huanglongbing through citrus groves is used as a case study for modeling an emerging epidemic in the presence of a control. Specifically, the spread of the disease is modeled as a susceptible-exposed-infectious-detected-removed epidemic, where the exposure and infectious times are not observed, detection times are censored, removal times are known, and the disease is spreading through a heterogeneous host population with trees of different age and susceptibility. We show that it is possible to characterize the disease transmission process under these conditions. Two innovations in our work are (i) accounting for control measures via time dependence of the infectious process and (ii) including seasonal and host age effects in the model of the latent period. By estimating parameters in different subregions of a large commercially cultivated orchard, we establish a temporal pattern of invasion, host age dependence of the dispersal parameters, and a close to linear relationship between primary and secondary infectious rates. The model can be used to simulate Huanglongbing epidemics to assess economic costs and potential benefits of putative control scenarios. PMID:24711393

Nursing Activities for Patients With Chronic Disease in Primary Care Settings: A Practice Analysis.

PubMed

Poitras, Marie-Eve; Chouinard, Maud-Christine; Gallagher, Frances; Fortin, Martin

Nurses in primary care organizations play a central role for patients with chronic disease. Lack of clarity in role description may be associated with underutilization of nurse competencies that could benefit the growing population of patients with chronic disease. The purpose of the research was to describe nursing activities in primary care settings with patients with chronic disease. A Web-based survey was sent to nurses practicing in Family Medicine Groups in the Canadian Province of Québec. Participants rated the frequency with which they carried out nursing activities in five domains: (a) global assessment, (b) care and case management, (c) health promotion, (d) nurse-physician collaboration, and (e) planning services for patients with chronic disease. Findings were summarized with descriptive statistics (means, standard deviations, and ranges). The survey was completed by 266 of the 322 nurses who received the survey (82.6%). Activities in the health promotion and global assessment of the patient domains were carried out most frequently. Planning services for patients with chronic disease were least frequently performed. This study provides a broad description of nursing activities with patients with chronic disease in primary care. The findings provide a baseline for clinicians and researchers to document and improve nursing activities for optimal practice for patients with chronic disease.

Reduced coronary flow and resistance reserve in primary scleroderma myocardial disease

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

Nitenberg, A.; Foult, J.M.; Kahan, A.

1986-08-01

The maximum coronary vasodilator capacity after intravenous dipyridamole (0.14 mg X kg-1 X min-1 X 4 minutes) was studied in seven patients with primary scleroderma myocardial disease and compared to that of seven control subjects. Hemodynamic data and left ventricular angiographic data were not different in the two groups. The coronary flow reserve was evaluated by the dipyridamole/basal coronary sinus blood flow ratio (D/B CSBF) and the coronary resistance reserve by the dipyridamole/basal coronary resistance ratio (D/B CR). Coronary reserve was greatly impaired in the group with primary scleroderma myocardial disease: D/B CSBF was lower than in the control groupmore » (2.54 +/- 1.37 vs 4.01 +/- 0.56, respectively; p less than 0.05) and D/B CR was higher than in the control group (0.47 +/- 0.25 vs 0.23 +/- 0.04, respectively; p less than 0.05). Such a decreased coronary flow and resistance reserve in patients with primary scleroderma myocardial disease was not explained by an alteration of left ventricular function. It may be an important contributing factor in the pathogenesis of primary scleroderma myocardial disease.« less

Pulmonary sporotrichosis: case series and systematic analysis of literature on clinico-radiological patterns and management outcomes.

PubMed

Aung, Ar Kar; Teh, Bing Mei; McGrath, Christopher; Thompson, Philip J

2013-07-01

Pulmonary infections by Sporothrix spp. manifest radiologically as cavitary or non-cavitary disease depending on whether the infection is primary pulmonary or multifocal sporotrichosis. Despite current guidelines, the optimal management for pulmonary sporotrichosis remains unclear. In order to clarify this, we present two cases of pulmonary sporotrichosis, as well as the results of a comprehensive literature review of treatment outcomes based on clinico-radiological presentation patterns of the disease. A literature search of all case reports in English language over the last 50 years (1960-2010) was conducted. Data on patient characteristics, risk factors, clinico-radiological patterns, treatment modalities and outcomes were collected and analyzed. A total of 86 cases were identified, i.e., 64 (74.4%) primary pulmonary and 22 (25.6%) multifocal sporotrichosis. Radiologically, primary pulmonary disease was commonly characterized by cavity formation which was lacking in multifocal infections (P = 0.0001). Immunosuppressant use was more common in multifocal sporotrichosis (P = 0.0001), while hemoptysis was more common in primary pulmonary form (P = 0.01). No other differences in patient characteristics or risk factors were noted. Extra-pulmonary multifocal sporotrichosis most commonly involved skin (81.8%) and joints (45.4%). For patients with cavitary primary pulmonary sporotrichosis, outcomes from medical therapy alone were inferior to surgical intervention (P = 0.02). However, for both primary pulmonary and multifocal sporotrichosis with non-cavitary disease, medical therapy alone provided good outcomes. Only 12 (16.7%) cases were treated with itraconazole. Treatment of pulmonary sporotrichosis should be guided by the clinico-radiological patterns of presentation. Medical therapy alone is likely sufficient for non-cavitary disease while early surgery should be considered for cavitary primary pulmonary sporotrichosis. The experience in treating cavitary disease with itraconazole alone is limited and further data are required.

28 CFR 79.62 - Criteria for eligibility for claims by ore transporters.

Code of Federal Regulations, 2010 CFR

2010-07-01

... beginning on January 1, 1942, and ending on December 31, 1971; and (c) The claimant contracted primary lung cancer, a nonmalignant respiratory disease, primary renal cancer, or chronic renal disease (including...

Enablers and inhibitors of the implementation of the Casalud Model, a Mexican innovative healthcare model for non-communicable disease prevention and control.

PubMed

Tapia-Conyer, Roberto; Saucedo-Martinez, Rodrigo; Mujica-Rosales, Ricardo; Gallardo-Rincon, Hector; Campos-Rivera, Paola Abril; Lee, Evan; Waugh, Craig; Guajardo, Lucia; Torres-Beltran, Braulio; Quijano-Gonzalez, Ursula; Soni-Gallardo, Lidia

2016-07-22

The Mexican healthcare system is under increasing strain due to the rising prevalence of non-communicable diseases (especially type 2 diabetes), mounting costs, and a reactive curative approach focused on treating existing diseases and their complications rather than preventing them. Casalud is a comprehensive primary healthcare model that enables proactive prevention and disease management throughout the continuum of care, using innovative technologies and a patient-centred approach. Data were collected over a 2-year period in eight primary health clinics (PHCs) in two states in central Mexico to identify and assess enablers and inhibitors of the implementation process of Casalud. We used mixed quantitative and qualitative data collection tools: surveys, in-depth interviews, and participant and non-participant observations. Transcripts and field notes were analyzed and coded using Framework Analysis, focusing on defining and describing enablers and inhibitors of the implementation process. We identified seven recurring topics in the analyzed textual data. Four topics were categorized as enablers: political support for the Casalud model, alignment with current healthcare trends, ongoing technical improvements (to ease adoption and support), and capacity building. Three topics were categorized as inhibitors: administrative practices, health clinic human resources, and the lack of a shared vision of the model. Enablers are located at PHCs and across all levels of government, and include political support for, and the technological validity of, the model. The main inhibitor is the persistence of obsolete administrative practices at both state and PHC levels, which puts the administrative feasibility of the model's implementation in jeopardy. Constructing a shared vision around the model could facilitate the implementation of Casalud as well as circumvent administrative inhibitors. In order to overcome PHC-level barriers, it is crucial to have an efficient and straightforward adaptation and updating process for technological tools. One of the key lessons learned from the implementation of the Casalud model is that a degree of uncertainty must be tolerated when quickly scaling up a healthcare intervention. Similar patient-centred technology-based models must remain open to change and be able to quickly adapt to changing circumstances.

[Primary and secondary prevention procedures of temporo-mandibular joint disease in the evolutive age].

PubMed

Ciavarella, D; Mastrovincenzo, M; Sabatucci, A; Campisi, G; Di Cosola, M; Suriano, M; Lo Muzio, L

2009-02-01

In the last years prevention of temporomandiboular joint (TMJ) disease had acquired great importance. According to the neuro-occlusal rehabilitation (RNO) it is possible to say that TMJ disease starts since first years of life. So it is important both for dentist and for pediatric know what are the conditions and the atypical functions which predispose to this pathology. The aim of this work was to show how it is possible to intercept since primary teeth and the correct norms of primary and secondary prevention.

Comparison of primary care models in the prevention of cardiovascular disease - a cross sectional study

PubMed Central

2011-01-01

Background Primary care providers play an important role in preventing and managing cardiovascular disease. This study compared the quality of preventive cardiovascular care delivery amongst different primary care models. Methods This is a secondary analysis of a larger randomized control trial, known as the Improved Delivery of Cardiovascular Care (IDOCC) through Outreach Facilitation. Using baseline data collected through IDOCC, we conducted a cross-sectional study of 82 primary care practices from three delivery models in Eastern Ontario, Canada: 43 fee-for-service, 27 blended-capitation and 12 community health centres with salary-based physicians. Medical chart audits from 4,808 patients with or at high risk of developing cardiovascular disease were used to examine each practice's adherence to ten evidence-based processes of care for diabetes, chronic kidney disease, dyslipidemia, hypertension, weight management, and smoking cessation care. Generalized estimating equation models adjusting for age, sex, rurality, number of cardiovascular-related comorbidities, and year of data collection were used to compare guideline adherence amongst the three models. Results The percentage of patients with diabetes that received two hemoglobin A1c tests during the study year was significantly higher in community health centres (69%) than in fee-for-service (45%) practices (Adjusted Odds Ratio (AOR) = 2.4 [95% CI 1.4-4.2], p = 0.001). Blended capitation practices had a significantly higher percentage of patients who had their waistlines monitored than in fee-for-service practices (19% vs. 5%, AOR = 3.7 [1.8-7.8], p = 0.0006), and who were recommended a smoking cessation drug when compared to community health centres (33% vs. 16%, AOR = 2.4 [1.3-4.6], p = 0.007). Overall, quality of diabetes care was higher in community health centres, while smoking cessation care and weight management was higher in the blended-capitation models. Fee-for-service practices had the greatest gaps in care, most noticeably in diabetes care and weight management. Conclusions This study adds to the evidence suggesting that primary care delivery model impacts quality of care. These findings support current Ontario reforms to move away from the traditional fee-for-service practice. Trial Registration ClinicalTrials.gov: NCT00574808 PMID:22008366

Oral primary care: an analysis of its impact on the incidence and mortality rates of oral cancer.

PubMed

Rocha, Thiago Augusto Hernandes; Thomaz, Erika Bárbara Abreu Fonseca; da Silva, Núbia Cristina; de Sousa Queiroz, Rejane Christine; de Souza, Marta Rovery; Barbosa, Allan Claudius Queiroz; Thumé, Elaine; Rocha, João Victor Muniz; Alvares, Viviane; de Almeida, Dante Grapiuna; Vissoci, João Ricardo Nickenig; Staton, Catherine Ann; Facchini, Luiz Augusto

2017-10-30

Oral cancer is a potentially fatal disease, especially when diagnosed in advanced stages. In Brazil, the primary health care (PHC) system is responsible for promoting oral health in order to prevent oral diseases. However, there is insufficient evidence to assess whether actions of the PHC system have some effect on the morbidity and mortality from oral cancer. The purpose of this study was to analyze the effect of PHC structure and work processes on the incidence and mortality rates of oral cancer after adjusting for contextual variables. An ecological, longitudinal and analytical study was carried out. Data were obtained from different secondary data sources, including three surveys that were nationally representative of Brazilian PHC and carried out over the course of 10 years (2002-2012). Data were aggregated at the state level at different times. Oral cancer incidence and mortality rates, standardized by age and gender, served as the dependent variables. Covariables (sociodemographic, structure of basic health units, and work process in oral health) were entered in the regression models using a hierarchical approach based on a theoretical model. Analysis of mixed effects with random intercept model was also conducted (alpha = 5%). The oral cancer incidence rate was positively association with the proportion of of adults over 60 years (β = 0.59; p = 0.010) and adult smokers (β = 0.29; p = 0.010). The oral cancer related mortality rate was positively associated with the proportion of of adults over 60 years (β = 0.24; p < 0.001) and the performance of preventative and diagnostic actions for oral cancer (β = 0.02; p = 0.002). Mortality was inversely associated with the coverage of primary care teams (β = -0.01; p < 0.006) and PHC financing (β = -0.52 -9 ; p = 0.014). In Brazil, the PHC structure and work processes have been shown to help reduce the mortality rate of oral cancer, but not the incidence rate of the disease. We recommend expanding investments in PHC in order to prevent oral cancer related deaths.

Auditing chronic disease care: Does it make a difference?

PubMed

Essel, Vivien; van Vuuren, Unita; De Sa, Angela; Govender, Srini; Murie, Katie; Schlemmer, Arina; Gunst, Colette; Namane, Mosedi; Boulle, Andrew; de Vries, Elma

2015-06-26

An integrated audit tool was developed for five chronic diseases, namely diabetes, hypertension, asthma, chronic obstructive pulmonary disease and epilepsy. Annual audits have been done in the Western Cape Metro district since 2009. The year 2012 was the first year that all six districts in South Africa's Western Cape Province participated in the audit process. To determine whether clinical audits improve chronic disease care in health districts over time. Western Cape Province, South Africa. Internal audits were conducted of primary healthcare facility processes and equipment availability as well as a folder review of 10 folders per chronic condition per facility. Random systematic sampling was used to select the 10 folders for the folder review. Combined data for all facilities gave a provincial overview and allowed for comparison between districts. Analysis was done comparing districts that have been participating in the audit process from 2009 to 2010 ('2012 old') to districts that started auditing recently ('2012 new'). The number of facilities audited has steadily increased from 29 in 2009 to 129 in 2012. Improvements between different years have been modest, and the overall provincial average seemed worse in 2012 compared to 2011. However, there was an improvement in the '2012 old' districts compared to the '2012 new' districts for both the facility audit and the folder review, including for eight clinical indicators, with '2012 new' districts being less likely to record clinical processes (OR 0.25, 95% CI 0.21-0.31). These findings are an indication of the value of audits to improve care processes over the long term. It is hoped that this improvement will lead to improved patient outcomes.

Auditing chronic disease care: Does it make a difference?

PubMed Central

van Vuuren, Unita; De Sa, Angela; Govender, Srini; Murie, Katie; Schlemmer, Arina; Gunst, Colette; Namane, Mosedi; Boulle, Andrew; de Vries, Elma

2015-01-01

Background An integrated audit tool was developed for five chronic diseases, namely diabetes, hypertension, asthma, chronic obstructive pulmonary disease and epilepsy. Annual audits have been done in the Western Cape Metro district since 2009. The year 2012 was the first year that all six districts in South Africa's Western Cape Province participated in the audit process. Aim To determine whether clinical audits improve chronic disease care in health districts over time. Setting Western Cape Province, South Africa. Methods Internal audits were conducted of primary healthcare facility processes and equipment availability as well as a folder review of 10 folders per chronic condition per facility. Random systematic sampling was used to select the 10 folders for the folder review. Combined data for all facilities gave a provincial overview and allowed for comparison between districts. Analysis was done comparing districts that have been participating in the audit process from 2009 to 2010 (‘2012 old’) to districts that started auditing recently (‘2012 new’). Results The number of facilities audited has steadily increased from 29 in 2009 to 129 in 2012. Improvements between different years have been modest, and the overall provincial average seemed worse in 2012 compared to 2011. However, there was an improvement in the ‘2012 old’ districts compared to the ‘2012 new’ districts for both the facility audit and the folder review, including for eight clinical indicators, with ‘2012 new’ districts being less likely to record clinical processes (OR 0.25, 95% CI 0.21–0.31). Conclusion These findings are an indication of the value of audits to improve care processes over the long term. It is hoped that this improvement will lead to improved patient outcomes. PMID:26245615

A mobile phone user interface for image-based dietary assessment

NASA Astrophysics Data System (ADS)

Ahmad, Ziad; Khanna, Nitin; Kerr, Deborah A.; Boushey, Carol J.; Delp, Edward J.

2014-02-01

Many chronic diseases, including obesity and cancer, are related to diet. Such diseases may be prevented and/or successfully treated by accurately monitoring and assessing food and beverage intakes. Existing dietary assessment methods such as the 24-hour dietary recall and the food frequency questionnaire, are burdensome and not generally accurate. In this paper, we present a user interface for a mobile telephone food record that relies on taking images, using the built-in camera, as the primary method of recording. We describe the design and implementation of this user interface while stressing the solutions we devised to meet the requirements imposed by the image analysis process, yet keeping the user interface easy to use.

A Mobile Phone User Interface for Image-Based Dietary Assessment

PubMed Central

Ahmad, Ziad; Khanna, Nitin; Kerr, Deborah A.; Boushey, Carol J.; Delp, Edward J.

2016-01-01

Many chronic diseases, including obesity and cancer, are related to diet. Such diseases may be prevented and/or successfully treated by accurately monitoring and assessing food and beverage intakes. Existing dietary assessment methods such as the 24-hour dietary recall and the food frequency questionnaire, are burdensome and not generally accurate. In this paper, we present a user interface for a mobile telephone food record that relies on taking images, using the built-in camera, as the primary method of recording. We describe the design and implementation of this user interface while stressing the solutions we devised to meet the requirements imposed by the image analysis process, yet keeping the user interface easy to use. PMID:28572696

A Mobile Phone User Interface for Image-Based Dietary Assessment.

PubMed

Ahmad, Ziad; Khanna, Nitin; Kerr, Deborah A; Boushey, Carol J; Delp, Edward J

2014-02-02

Many chronic diseases, including obesity and cancer, are related to diet. Such diseases may be prevented and/or successfully treated by accurately monitoring and assessing food and beverage intakes. Existing dietary assessment methods such as the 24-hour dietary recall and the food frequency questionnaire, are burdensome and not generally accurate. In this paper, we present a user interface for a mobile telephone food record that relies on taking images, using the built-in camera, as the primary method of recording. We describe the design and implementation of this user interface while stressing the solutions we devised to meet the requirements imposed by the image analysis process, yet keeping the user interface easy to use.

Astrogliopathology in neurological, neurodevelopmental and psychiatric disorders

PubMed Central

Verkhratsky, Alexei; Parpura, Vladimir

2015-01-01

Astroglial cells represent a main element in the maintenance of homeostasis and providing defense to the brain. Consequently, their dysfunction underlies many, if not all, neurological, neuropsychiatric and neurodegenerative disorders. General astrogliopathy is evident in diametrically opposing morpho-functional changes in astrocytes, i.e. their hypertrophy along with reactivity or atrophy with asthenia. Neurological disorders with astroglial participation can be genetic, of which Alexander disease is a primary sporadic astrogliopathy, environmentally caused, such as heavy metal encephalopathies, or neurodevelopmental in origin. Astroglia also play a role in major neuropsychiatric disorders, ranging from schizophrenia to depression, as well as in additive disorders. Furthermore, astroglia contribute to neurodegenerative processes seen in amyotrophic lateral sclerosis, Alzheimer’s and Huntington’s diseases. PMID:25843667

Patient-derived Mammosphere and Xenograft Tumour Initiation Correlates with Progression to Metastasis.

PubMed

Eyre, Rachel; Alférez, Denis G; Spence, Kath; Kamal, Mohamed; Shaw, Frances L; Simões, Bruno M; Santiago-Gómez, Angélica; Sarmiento-Castro, Aida; Bramley, Maria; Absar, Mohammed; Saad, Zahida; Chatterjee, Sumohan; Kirwan, Cliona; Gandhi, Ashu; Armstrong, Anne C; Wardley, Andrew M; O'Brien, Ciara S; Farnie, Gillian; Howell, Sacha J; Clarke, Robert B

2016-12-01

Breast cancer specific mortality results from tumour cell dissemination and metastatic colonisation. Identification of the cells and processes responsible for metastasis will enable better prevention and control of metastatic disease, thus reducing relapse and mortality. To better understand these processes, we prospectively collected 307 patient-derived breast cancer samples (n = 195 early breast cancers (EBC) and n = 112 metastatic samples (MBC)). We assessed colony-forming activity in vitro by growing isolated cells in both primary (formation) and secondary (self-renewal) mammosphere culture, and tumour initiating activity in vivo through subcutaneous transplantation of fragments or cells into mice. Metastatic samples formed primary mammosphere colonies significantly more frequently than early breast cancers and had significantly higher primary mammosphere colony formation efficiency (0.9 % vs. 0.6 %; p < 0.0001). Tumour initiation in vivo was significantly higher in metastatic than early breast cancer samples (63 % vs. 38 %, p = 0.04). Of 144 breast cancer samples implanted in vivo, we established 20 stable patient-derived xenograft (PDX) models at passage 2 or greater. Lung metastases were detected in mice from 14 PDX models. Mammosphere colony formation in vitro significantly correlated with the ability of a tumour to metastasise to the lungs in vivo (p = 0.05), but not with subcutaneous tumour initiation. In summary, the breast cancer stem cell activities of colony formation and tumour initiation are increased in metastatic compared to early samples, and predict metastasis in vivo. These results suggest that breast stem cell activity will predict for poor outcome tumours, and therapy targeting this activity will improve outcomes for patients with metastatic disease.

A scoping literature review of collaboration between primary care and public health.

PubMed

Martin-Misener, Ruth; Valaitis, Ruta; Wong, Sabrina T; Macdonald, Marjorie; Meagher-Stewart, Donna; Kaczorowski, Janusz; O-Mara, Linda; Savage, Rachel; Austin, Patricia

2012-10-01

The purpose of this scoping literature review was to determine what is known about: 1) structures and processes required to build successful collaborations between primary care (PC) and public health (PH); 2) outcomes of such collaborations; and 3) markers of their success. Collaboration between PC and PH is believed to enable more effective individual and population services than what might be achieved by either alone. The study followed established methods for a scoping literature review and was guided by a framework that identifies systemic, organizational and interactional determinants for collaboration. The review was restricted to articles published between 1988 and 2008. Published quantitative and qualitative primary studies, evaluation research, systematic and other types of reviews, as well as descriptive accounts without an explicit research design, were included if they addressed either the structures or processes to build collaboration or the outcomes or markers of such collaboration, and were published in English. The combined search strategy yielded 6125 articles of which 114 were included. Systemic-level factors influencing collaboration included: government involvement, policy and fit with local needs; funding and resource factors, power and control issues; and education and training. Lack of a common agenda; knowledge and resource limitations; leadership, management and accountability issues; geographic proximity of partners; and shared protocols, tools and information sharing were influential at the organizational level. Interpersonal factors included having a shared purpose; philosophy and beliefs; clear roles and positive relationships; and effective communication and decision-making strategies. Reported benefits of collaboration included: improved chronic disease management; communicable disease control; and maternal child health. More research is needed to explore the conditions and contexts in which collaboration between PC and PH makes most sense and potential gains outweigh the associated risks and costs.

The ocular pathology of Norrie disease in a fetus of 11 weeks' gestational age.

PubMed

Parsons, M A; Curtis, D; Blank, C E; Hughes, H N; McCartney, A C

1992-01-01

The ocular pathology of Norrie disease was studied for the first time in a fetus of 11 weeks' gestation, following prenatal diagnosis using genetic markers for Norrie disease and elective abortion. The eyes were histologically normal, with no evidence of primary neuroectodermal maldevelopment of the retina, previously postulated to be the cause of the ocular changes. We believe that the retinal and other manifestations of Norrie disease are the result of a primary abnormality of vascular proliferation, probably in relation to persistent hyperplastic primary vitreous after approximately 14 weeks' gestation. We postulate that the ocular and otological effects of Norrie disease may be due to a genetically mediated abnormality of secretion of, or sensitivity to, angiogenic growth factors at endodermal-neuroectodermal interfaces during fetal and postnatal development.

Ruling out coronary artery disease in primary care: development and validation of a simple prediction rule.

PubMed

Bösner, Stefan; Haasenritter, Jörg; Becker, Annette; Karatolios, Konstantinos; Vaucher, Paul; Gencer, Baris; Herzig, Lilli; Heinzel-Gutenbrunner, Monika; Schaefer, Juergen R; Abu Hani, Maren; Keller, Heidi; Sönnichsen, Andreas C; Baum, Erika; Donner-Banzhoff, Norbert

2010-09-07

Chest pain can be caused by various conditions, with life-threatening cardiac disease being of greatest concern. Prediction scores to rule out coronary artery disease have been developed for use in emergency settings. We developed and validated a simple prediction rule for use in primary care. We conducted a cross-sectional diagnostic study in 74 primary care practices in Germany. Primary care physicians recruited all consecutive patients who presented with chest pain (n = 1249) and recorded symptoms and findings for each patient (derivation cohort). An independent expert panel reviewed follow-up data obtained at six weeks and six months on symptoms, investigations, hospital admissions and medications to determine the presence or absence of coronary artery disease. Adjusted odds ratios of relevant variables were used to develop a prediction rule. We calculated measures of diagnostic accuracy for different cut-off values for the prediction scores using data derived from another prospective primary care study (validation cohort). The prediction rule contained five determinants (age/sex, known vascular disease, patient assumes pain is of cardiac origin, pain is worse during exercise, and pain is not reproducible by palpation), with the score ranging from 0 to 5 points. The area under the curve (receiver operating characteristic curve) was 0.87 (95% confidence interval [CI] 0.83-0.91) for the derivation cohort and 0.90 (95% CI 0.87-0.93) for the validation cohort. The best overall discrimination was with a cut-off value of 3 (positive result 3-5 points; negative result

Development of a core set of quality indicators for paediatric primary care practices in Europe, COSI-PPC-EU.

PubMed

Ewald, Dominik A; Huss, Gottfried; Auras, Silke; Caceres, Juan Ruiz-Canela; Hadjipanayis, Adamos; Geraedts, Max

2018-06-01

Paediatric ambulatory healthcare systems in Europe are, because of historical reasons, diverse and show strikingly different outcomes. All across Europe, the benchmarking of structures, processes and outcomes could reveal opportunities for improving Paediatric Primary Care (PPC). The aim of this study was to develop a set of Quality Indicators (QIs) to assess and monitor PPC in Europe. In a three-step process, we used the available external evidence and European expert consensus in a modified RAND/UCLA Appropriateness Method (RAM) to develop an indicator set. (1) A broad literature and online research of published QI and guidelines yielded an inventory of 1516 QI. (2) A collaborative panel of paediatric senior experts from the European Academy of Paediatrics (EAP) and the European Confederation of Primary Care Paediatricians (ECPCP) from 15 European countries participated in a first consensus process to reduce the initial indicator inventory by eliminating not PPC-focused indicators and duplicates. (3) In a second consensus process, the panel rated the QI regarding validity and feasibility. The final QI set "COSI-PPC-EU" consists of 42 indicators in five categories of PPC: (A) health promotion/prevention/screening (13 QI), (B) acute care (9 QI), (C) chronic care (8 QI), (D) practice management (3 QI) and (E) patient safety (9 QI). COSI-PPC-EU represents a consented set of a limited number of valid quality indicators for the application in paediatric primary care in different healthcare systems throughout Europe. What is Known: • Paediatric ambulatory healthcare systems in Europe are diverse and show strikingly different outcomes. • There are known gaps in quality performance measures of paediatric primary care in Europe. Pre-existing sets of quality indicators are predominantly limited to national populations, specific diseases and hospital care. What is New: • A set of 42 quality indicators for primary paediatric care in Europe was developed in a multi-country collaborative effort. The method combined a systematic literature review and a consensus process among European paediatric experts. • The quality indicator set can facilitate quality improvement of PPC. After studying the feasibility, providers can use COSI-PPC-EU to monitor, compare and improve performance of practices, regions and countries.

The role of the fallopian tube in the origin of ovarian cancer

PubMed Central

Erickson, Britt K.; Conner, Michael G.; Landen, Charles N.

2014-01-01

Advanced cases of epithelial ovarian, primary peritoneal, and primary tubal malignancies have a relatively poor prognosis and collectively remain the most deadly of all gynecologic malignancies. Although traditionally thought of as one disease process, ongoing research suggests that there is not 1 single site or cell type from which these cancers arise. A majority of the serous tumors appear to originate from dysplastic lesions in the distal fallopian tube. Therefore, what we have traditionally considered “ovarian” cancer may in fact be tubal in origin. In this article, we will review epithelial ovarian cancer classification and genetics, theories regarding cells of origin with a focus on tubal intraepithelial carcinoma, and implications for prevention and screening. PMID:23583217

Reducing heart disease through the vegetarian diet using primary prevention.

PubMed

Sticher, Megan A; Smith, Christine B; Davidson, Susan

2010-03-01

To evaluate research on the vegetarian diet for its safety, effectiveness in reducing heart disease, special considerations, contraindications, and its association with decreased cardiovascular disease risk. Selected research and evidence-based dietary guidelines found by searching CINAHL, PubMed, Ovid databases, and the World Wide Web. A carefully planned vegetarian diet with adequate supplementation may be effective for primary prevention of heart disease. The vegetarian diet is cost effective, safe, and relatively easy to implement. Improved dietary choices can help improve many chronic conditions. Guidelines for proper nutrition within a vegetarian lifestyle are readily accessible to patients and professionals alike. Referral to a dietitian is an appropriate option in primary care settings.

Pathogenic Leptospira interrogans Exoproteins Are Primarily Involved in Heterotrophic Processes

PubMed Central

Eshghi, Azad; Pappalardo, Elisa; Hester, Svenja; Thomas, Benjamin; Pretre, Gabriela

2015-01-01

Leptospirosis is a life-threatening and emerging zoonotic disease with a worldwide annual occurrence of more than 1 million cases. Leptospirosis is caused by spirochetes belonging to the genus Leptospira. The mechanisms of disease manifestation in the host remain elusive, and the roles of leptospiral exoproteins in these processes have yet to be determined. Our aim in this study was to assess the composition and quantity of exoproteins of pathogenic Leptospira interrogans and to construe how these proteins contribute to disease pathogenesis. Label-free quantitative mass spectrometry of proteins obtained from Leptospira spirochetes cultured in vitro under conditions mimicking infection identified 325 exoproteins. The majority of these proteins are conserved in the nonpathogenic species Leptospira biflexa, and proteins involved in metabolism and energy-generating functions were overrepresented and displayed the highest relative abundance in culture supernatants. Conversely, proteins of unknown function, which represent the majority of pathogen-specific proteins (presumably involved in virulence mechanisms), were underrepresented. Characterization of various L. interrogans exoprotein mutants in the animal infection model revealed host mortality rates similar to those of hosts infected with wild-type L. interrogans. Collectively, these results indicate that pathogenic Leptospira exoproteins primarily function in heterotrophic processes (the processes by which organisms utilize organic substances as nutrient sources) to maintain the saprophytic lifestyle rather than the virulence of the bacteria. The underrepresentation of proteins homologous to known virulence factors, such as toxins and effectors in the exoproteome, also suggests that disease manifesting from Leptospira infection is likely caused by a combination of the primary and potentially moonlight functioning of exoproteins. PMID:25987703

The value of animal to study immunopathology of primary human Sjögren's syndrome symptoms

PubMed Central

Donate, Amy; Voigt, Alexandria; Nguyen, Cuong Q.

2018-01-01

Sjögren’s syndrome (SjS) is a complex chronic autoimmune disease of multifactorial etiology that results in eventual loss of secretory function in the exocrine glands. The challenges towards finding a therapeutic prevention or treatment for SjS are due primarily to a lack of understanding in the pathophysiological and clinical progression of the disease. In order to circumnavigate this problem, there is a need for appropriate animal models that resemble the major phenotypes of human SjS and deliver a clear underlying biological or molecular mechanism capable of defining various aspects for the disease. Here, we present an overview of SjS mouse models that are providing insight into the autoimmune process of SjS and advance our focus on potential diagnostic and therapeutic targets. PMID:24506531

Comparative biology of the neuronal ceroid-lipofuscinoses (NCL): an overview.

PubMed

Jolly, R D

1995-06-05

Multiple forms of ceroid-lipofuscinosis occur in human beings and animals. They are characterized by brain and retinal atrophy associated with selective necrosis of neurons. This neurodegenerative disease appears associated with the disease process rather than storage of fluorescent lipopigment per se, and there is now growing evidence that pathogenesis may involve mitochondria rather than a primary defect of lysosomal catabolism. Of the forms of ceroid-lipofuscinosis studied, most but not all reflect accumulation of subunit c of mitochondrial ATP synthase. If there is a common denominator between all forms other than the presence of fluorescent lipopigment, then it may be the accumulation of hydrophobic protein. Analogous diseases in animals can be expected to reflect the same spectrum of biochemical changes, and they warrant in-depth study to help understand the pathogenesis and heterogeneity of the group.

[Etiological analysis of 264 cases with chronic kidney disease stage 2 to 5 in children].

PubMed

Miao, Qianfan; Shen, Qian; Xu, Hong; Sun, Li; Tang, Xiaoshan; Fang, Xiaoyan; Liu, Haimei; Zhai, Yihui; Bi, Yunli; Wang, Xiang; Chen, Hong

2015-09-01

To study and summarize the etiology of children patients with chronic kidney disease (CKD) stage 2 to 5 seen in Children's Hospital of Fudan University from Jan. 2004 to Dec. 2013. By complying with the NKF-K/DOQI guidelines, we collected data of 264 cases of children patients with CKD stage 2-5 from Jan. 2004 to Dec. 2013 in the medical record system of Children's Hospital of Fudan University. And we retrospectively analyzed their age and CKD stage at first diagnosis, primary diseases, complications, etc. In the collected 264 cases, 52 cases (19.7%) were diagnosed at stage 2, 67 (25.4%) at stage 3, 52 (19.7%) at stage 4 and 93 (35.2%) at stage 5. For disease causes, 116 cases (43.9%) had congenital anomalies of the kidney and urinary tract (CAKUT), 61 cases (23.1%) had glomerular disease, 15 (5.7%) had hereditary kidney disease, 14 (5.3%) had other diseases and in 58 cases (22.0%) the causes of disease were unknown. In the group with age between 0 and 3.0 and 3.1 and 6.0 years, 57.1% (24 cases) and 60.0% (30 cases) had primary disease with CAKUT. In the group with age older than 10 years, 49.2% (30 cases) had primary disease with glomerular disease and 32.0% (32 cases) with unknown causes. The major cause of CKD stage 2-5 in children in our hospital during the last ten years was CAKUT (43.9%), followed by glomerular disease (23.1%). The primary diseases of CKD were significantly different between the 2 age groups. CAKUT was more common in infants and preschool children while for adolescents, glomerular disease was the major cause.

Wait times to rheumatology care for patients with rheumatic diseases: a data linkage study of primary care electronic medical records and administrative data.

PubMed

Widdifield, Jessica; Bernatsky, Sasha; Thorne, J Carter; Bombardier, Claire; Jaakkimainen, R Liisa; Wing, Laura; Paterson, J Michael; Ivers, Noah; Butt, Debra; Lyddiatt, Anne; Hofstetter, Catherine; Ahluwalia, Vandana; Tu, Karen

2016-01-01

The Wait Time Alliance recently established wait time benchmarks for rheumatology consultations in Canada. Our aim was to quantify wait times to primary and rheumatology care for patients with rheumatic diseases. We identified patients from primary care practices in the Electronic Medical Record Administrative data Linked Database who had referrals to Ontario rheumatologists over the period 2000-2013. To assess the full care pathway, we identified dates of symptom onset, presentation in primary care and referral from electronic medical records. Dates of rheumatologist consultations were obtained by linking with physician service claims. We determined the duration of each phase of the care pathway (symptom onset to primary care encounter, primary care encounter to referral, and referral to rheumatologist consultation) and compared them with established benchmarks. Among 2430 referrals from 168 family physicians, 2015 patients (82.9%) were seen by 146 rheumatologists within 1 year of referral. Of the 2430 referrals, 2417 (99.5%) occurred between 2005 and 2013. The main reasons for referral were osteoarthritis (32.4%) and systemic inflammatory rheumatic diseases (30.6%). Wait times varied by diagnosis and geographic region. Overall, the median wait time from referral to rheumatologist consultation was 74 (interquartile range 27-101) days; it was 66 (interquartile range 18-84) days for systemic inflammatory rheumatic diseases. Wait time benchmarks were not achieved, even for the most urgent types of referral. For systemic inflammatory rheumatic diseases, most of the delays occurred before referral. Rheumatology wait times exceeded established benchmarks. Targeted efforts are needed to promote more timely access to both primary and rheumatology care. Routine linkage of electronic medical records with administrative data may help fill important gaps in knowledge about waits to primary and specialty care.

Protein kinase Cɛ inhibition restores megakaryocytic differentiation of hematopoietic progenitors from primary myelofibrosis patients.

PubMed

Masselli, E; Carubbi, C; Gobbi, G; Mirandola, P; Galli, D; Martini, S; Bonomini, S; Crugnola, M; Craviotto, L; Aversa, F; Vitale, M

2015-11-01

Among the three classic Philadelphia chromosome-negative myeloproliferative neoplasms, primary myelofibrosis (PMF) is the most severe in terms of disease biology, survival and quality of life. Abnormalities in the process of differentiation of PMF megakaryocytes (MKs) are a hallmark of the disease. Nevertheless, the molecular events that lead to aberrant megakaryocytopoiesis have yet to be clarified. Protein kinase Cɛ (PKCɛ) is a novel serine/threonine kinase that is overexpressed in a variety of cancers, promoting aggressive phenotype, invasiveness and drug resistance. Our previous findings on the role of PKCɛ in normal (erythroid and megakaryocytic commitment) and malignant (acute myeloid leukemia) hematopoiesis prompted us to investigate whether it could be involved in the pathogenesis of PMF MK-impaired differentiation. We demonstrate that PMF megakaryocytic cultures express higher levels of PKCɛ than healthy donors, which correlate with higher disease burden but not with JAK2V617F mutation. Inhibition of PKCɛ function (by a negative regulator of PKCɛ translocation) or translation (by target small hairpin RNA) leads to reduction in PMF cell growth, restoration of PMF MK differentiation and inhibition of PKCɛ-related anti-apoptotic signaling (Bcl-xL). Our data suggest that targeting PKCɛ directly affects the PMF neoplastic clone and represent a proof-of-concept for PKCɛ inhibition as a novel therapeutic strategy in PMF.

Disorders of erythrocyte hydration.

PubMed

Gallagher, Patrick G

2017-12-21

The erythrocyte contains a network of pathways that regulate salt and water content in the face of extracellular and intracellular osmotic perturbations. This allows the erythrocyte to maintain a narrow range of cell hemoglobin concentration, a process critical for normal red blood cell function and survival. Primary disorders that perturb volume homeostasis jeopardize the erythrocyte and may lead to its premature destruction. These disorders are marked by clinical, laboratory, and physiologic heterogeneity. Recent studies have revealed that these disorders are also marked by genetic heterogeneity. They have implicated roles for several proteins, PIEZO1, a mammalian mechanosensory protein; GLUT1, the glucose transporter; SLC4A1, the anion transporter; RhAG, the Rh-associated glycoprotein; KCNN4, the Gardos channel; and ABCB6, an adenosine triphosphate-binding cassette family member, in the maintenance of erythrocyte volume homeostasis. Secondary disorders of erythrocyte hydration include sickle cell disease, thalassemia, hemoglobin CC, and hereditary spherocytosis, where cellular dehydration may be a significant contributor to disease pathology and clinical complications. Understanding the pathways regulating erythrocyte water and solute content may reveal innovative strategies to maintain normal volume in disorders associated with primary or secondary cellular dehydration. These mechanisms will serve as a paradigm for other cells and may reveal new therapeutic targets for disease prevention and treatment beyond the erythrocyte. © 2017 by The American Society of Hematology.

A new computer-based counselling system for the promotion of physical activity in patients with chronic diseases--results from a pilot study.

PubMed

Becker, Annette; Herzberg, Dominikus; Marsden, Nicola; Thomanek, Sabine; Jung, Hartmut; Leonhardt, Corinna

2011-05-01

To develop a computer-based counselling system (CBCS) for the improvement of attitudes towards physical activity in chronically ill patients and to pilot its efficacy and acceptance in primary care. The system is tailored to patients' disease and motivational stage. During a pilot study in five German general practices, patients answered questions before, directly and 6 weeks after using the CBCS. Outcome criteria were attitudes and self-efficacy. Qualitative interviews were performed to identify acceptance indicators. Seventy-nine patients participated (mean age: 64.5 years, 53% males; 38% without previous computer experience). Patients' affective and cognitive attitudes changed significantly, self-efficacy showed only minor changes. Patients mentioned no difficulties in interacting with the CBCS. However, perception of the system's usefulness was inconsistent. Computer-based counselling for physical activity related attitudes in patients with chronic diseases is feasible, but the circumstances of use with respect to the target group and its integration into the management process have to be clarified in future studies. This study adds to the understanding of computer-based counselling in primary health care. Acceptance indicators identified in this study will be validated as part of a questionnaire on technology acceptability in a subsequent study. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

A Life Participation Approach to Primary Progressive Aphasia Intervention.

PubMed

Rogalski, Emily J; Khayum, Becky

2018-07-01

Primary progressive aphasia (PPA) is a clinical neurodegenerative dementia syndrome characterized by deficits in spoken and written word retrieval, word usage, and/or word comprehension. Currently, there are no effective treatments to reverse or halt the underlying disease process; however, speech-language therapy may be helpful. The Communication Bridge Care Model was developed to address the unique communication and quality of life needs of individuals living with PPA. The core elements include person-centered care with dyadic instruction for disease education, and counseling, along with tailored levels of impairment- and compensatory-based communication strategy training. Our multicomponent approach incorporates guidance from the Life Participation Approach for Aphasia, including client-directed assessment and interventions that aim to maximize functional communication and participation in desired life activities. The direct and indirect use of technology is integrated into our tailored model of care to facilitate achievement of the client's functional goals. Here, we describe how to practically apply the Communication Bridge Care Model across treatment settings, including case examples from the Communication Bridge research study. This approach to care provides an opportunity to maximize communication effectiveness and quality of life for individuals living with PPA throughout the course of disease. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Functionally different α-synuclein inclusions yield insight into Parkinson’s disease pathology

PubMed Central

Raiss, Christian C.; Braun, Theresa S.; Konings, Irene B. M.; Grabmayr, Heinrich; Hassink, Gerco C.; Sidhu, Arshdeep; le Feber, Joost; Bausch, Andreas R.; Jansen, Casper; Subramaniam, Vinod; Claessens, Mireille M. A. E.

2016-01-01

The formation of α-synuclein (α-S) amyloid aggregates, called Lewy bodies (LBs), is a hallmark of Parkinson’s disease (PD). The function of LBs in the disease process is however still unclear; they have been associated with both neuroprotection and toxicity. To obtain insight into this contradiction, we induced the formation of α-S inclusions, using three different induction methods in SH-SY5Y cells and rat-derived primary neuronal cells. Using confocal and STED microscopy we observed induction-dependent differences in α-S inclusion morphology, location and function. The aggregation of α-S in functionally different compartments correlates with the toxicity of the induction method measured in viability assays. The most cytotoxic treatment largely correlates with the formation of proteasome-associated, juxta-nuclear inclusions. With less toxic methods cytosolic deposits that are not associated with the proteasome are more prevalent. The distribution of α-S over at least two different types of inclusions is not limited to cell models, but is also observed in primary neuronal cells and in human mesencephalon. The existence of functionally different LBs, in vivo and in vitro, gives important insights in the impact of Lewy Body formation on neuronal functioning and may thereby provide a platform for discovering therapeutics. PMID:26984067

[Clinical and therapeutical considerations regarding the diagnosis and treatment in meconial disease].

PubMed

Sabetay, C; Ciobanu, O; Zavate, A; Ciucă, M; Malos, A; Marin-Diu, B

2010-01-01

The meconium disease represents a problem of great impact over the vital prognosis of the newborn, the mortality of this disease being rated in various studies between 30 and 50%. The meconial disease that reunites the meconial ileus and the meconial peritonitis is often associated with cystic fibrosis a disease of general impact over the entire organism increasing the gravity and influencing the vital prognosis of these patients. The authors' purpose is to evaluate the results obtained after the treatment of the meconial disease in the Pediatric Surgery Clinic of the Emergency Hospital of Craiova over a period of 10 years. The study has been made on a number of 16 cases of meconial ileus, plug and peritonitis analising the difficulty of the diagnostic process, the preoperative care as well as the possibilities of surgical treatment. The surgical treatment is composed of multiple procedures including simple suture of the bowel defect and segmentary bowel resections with primary anastomosis and/or secondary anastomosis after ileostoma. The mortality on the studied cases was of 37.5% despite recent progresses achieved in postoperative care of these type of patients.

Nonalcoholic Fatty Liver Disease Management: Dietary and Lifestyle Modifications.

PubMed

Nguyen, Vi; George, Jacob

2015-08-01

Nonalcoholic fatty liver disease (NAFLD) encompasses a spectrum of abnormalities that can range from bland liver fat (steatosis), to hepatic inflammation and liver injury (steatohepatitis). It is estimated that NAFLD will become the principal cause of liver disease in Western nations and the leading indication for liver transplantation. Advancements in disease recognition and management are therefore paramount. Although the development of new, reliable drug therapies is vital, lifestyle interventions remain the most effective treatment modality. In addition to weight loss as a primary measure of treatment success, there is growing recognition that other endpoints, including the prevention or delay of diabetes onset, reduced cardiovascular events, prevention of cancer, and improved overall mortality, are equally important outcomes that can be independently modified by lifestyle change. Moreover, NAFLD is inextricably part of a complex, systemic disease process that is linked with deeply entrenched maladaptive lifestyle behaviors. Thus, a holistic, multidisciplinary, and individualized approach to disease management will be the key to achieving any realistic population-level change. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Mitigating amphibian chytridiomycosis in nature

USGS Publications Warehouse

Garner, Trenton W. J.; Schmidt, Benedikt R.; Martel, An; Pasmans, Frank; Muths, Erin L.; Cunningham, Andrew A.; Weldon, Che; Fisher, Matthew C.; Bosch, Jaime

2016-01-01

Amphibians across the planet face the threat of population decline and extirpation caused by the disease chytridiomycosis. Despite consensus that the fungal pathogens responsible for the disease are conservation issues, strategies to mitigate their impacts in the natural world are, at best, nascent. Reducing risk associated with the movement of amphibians, non-amphibian vectors and other sources of infection remains the first line of defence and a primary objective when mitigating the threat of disease in wildlife. Amphibian-associated chytridiomycete fungi and chytridiomycosis are already widespread, though, and we therefore focus on discussing options for mitigating the threats once disease emergence has occurred in wild amphibian populations. All strategies have shortcomings that need to be overcome before implementation, including stronger efforts towards understanding and addressing ethical and legal considerations. Even if these issues can be dealt with, all currently available approaches, or those under discussion, are unlikely to yield the desired conservation outcome of disease mitigation. The decision process for establishing mitigation strategies requires integrated thinking that assesses disease mitigation options critically and embeds them within more comprehensive strategies for the conservation of amphibian populations, communities and ecosystems.

Hydroclimatic drivers, Water-borne Diseases, and Population Vulnerability in Bengal Delta

NASA Astrophysics Data System (ADS)

Akanda, A. S.; Jutla, A. S.

2012-04-01

Water-borne diarrheal disease outbreaks in the Bengal Delta region, such as cholera, rotavirus, and dysentery, show distinct seasonal peaks and spatial signatures in their origin and progression. However, the mechanisms behind these seasonal phenomena, especially the role of regional climatic and hydrologic processes behind the disease outbreaks, are not fully understood. Overall diarrheal disease prevalence and the population vulnerability to transmission mechanisms thus remain severely underestimated. Recent findings suggest that diarrheal incidence in the spring is strongly associated with scarcity of freshwater flow volumes, while the abundance of water in monsoon show strong positive correlation with autumn diarrheal burden. The role of large-scale ocean-atmospheric processes that tend to modulate meteorological, hydrological, and environmental conditions over large regions and the effects on the ecological states conducive to the vectors and triggers of diarrheal outbreaks over large geographic regions are not well understood. We take a large scale approach to conduct detailed diagnostic analyses of a range of climate, hydrological, and ecosystem variables to investigate their links to outbreaks, occurrence, and transmission of the most prevalent water-borne diarrheal diseases. We employ satellite remote sensing data products to track coastal ecosystems and plankton processes related to cholera outbreaks. In addition, we investigate the effect of large scale hydroclimatic extremes (e.g., droughts and floods, El Nino) to identify how diarrheal transmission and epidemic outbreaks are most likely to respond to shifts in climatic, hydrologic, and ecological changes over coming decades. We argue that controlling diarrheal disease burden will require an integrated predictive surveillance approach - a combination of prediction and prevention - with recent advances in climate-based predictive capabilities and demonstrated successes in primary and tertiary prevention in endemic regions.

mtDNA Mutations and Their Role in Aging, Diseases and Forensic Sciences

PubMed Central

Zapico, Sara C.; Ubelaker, Douglas H.

2013-01-01

Mitochondria are independent organelles with their own DNA. As a primary function, mitochondria produce the energy for the cell through Oxidative Phosphorylation (OXPHOS) in the Electron Transport Chain (ETC). One of the toxic products of this process is Reactive Oxygen Species (ROS), which can induce oxidative damage in macromolecules like lipids, proteins and DNA. Mitochondrial DNA (mtDNA) is less protected and has fewer reparation mechanisms than nuclear DNA (nDNA), and as such is more exposed to oxidative, mutation-inducing damage. This review analyzes the causes and consequences of mtDNA mutations and their relationship with the aging process. Neurodegenerative diseases, related with the aging, are consequences of mtDNA mutations resulting in a decrease in mitochondrial function. Also described are “mitochondrial diseases”, pathologies produced by mtDNA mutations and whose symptoms are related with mitochondrial dysfunction. Finally, mtDNA haplogroups are defined in this review; these groups are important for determination of geographical origin of an individual. Additionally, different haplogroups exhibit variably longevity and risk of certain diseases. mtDNA mutations in aging and haplogroups are of special interest to forensic science research. Therefore this review will help to clarify the key role of mtDNA mutations in these processes and support further research in this area. PMID:24307969

Implantable cardioverter defibrillator use for primary prevention in ischaemic and non-ischaemic heart disease-indications in the post-DANISH trial era: results of the European Heart Rhythm Association survey.

PubMed

Haugaa, Kristina H; Tilz, Roland; Boveda, Serge; Dobreanu, Dan; Sciaraffia, Elena; Mansourati, Jacques; Papiashvili, Giorgi; Dagres, Nikolaos

2017-04-01

Implantable cardioverter-defibrillator (ICD) is the standard of care for prevention of sudden cardiac death (SCD) in high-risk patients. For primary prevention of SCD, in patients with ischaemic heart disease, there is more robust data on the effect of ICD therapy compared with patients with non-ischaemic heart disease, but current real-life practice may differ substantially. The aim of this European Heart Rhythm Association survey was to evaluate the clinical practice regarding implantation of ICD for primary prevention among European countries in patients with non-ischaemic and ischaemic heart disease. Furthermore, we wanted to investigate the impact of the results of the recently published DANISH trial on clinical practice among European countries. In total, 48 centres from 17 different countries responded to the questionnaire. The majority did not implant ICD for primary prevention on a regular basis in patients with non-ischaemic heart disease despite current guidelines. Also, centres have changed their indications after the recent report on the efficacy of ICD in these patients. In patients with ischaemic heart disease, the guidelines for primary prevention ICD were followed on a regular basis, and no relevant change in indications were reported. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions, please email: journals.permissions@oup.com.

The Transcriptional Profile of Mesenchymal Stem Cell Populations in Primary Osteoporosis Is Distinct and Shows Overexpression of Osteogenic Inhibitors

PubMed Central

Benisch, Peggy; Schilling, Tatjana; Klein-Hitpass, Ludger; Frey, Sönke P.; Seefried, Lothar; Raaijmakers, Nadja; Krug, Melanie; Regensburger, Martina; Zeck, Sabine; Schinke, Thorsten; Amling, Michael; Ebert, Regina; Jakob, Franz

2012-01-01

Primary osteoporosis is an age-related disease characterized by an imbalance in bone homeostasis. While the resorptive aspect of the disease has been studied intensely, less is known about the anabolic part of the syndrome or presumptive deficiencies in bone regeneration. Multipotent mesenchymal stem cells (MSC) are the primary source of osteogenic regeneration. In the present study we aimed to unravel whether MSC biology is directly involved in the pathophysiology of the disease and therefore performed microarray analyses of hMSC of elderly patients (79–94 years old) suffering from osteoporosis (hMSC-OP). In comparison to age-matched controls we detected profound changes in the transcriptome in hMSC-OP, e.g. enhanced mRNA expression of known osteoporosis-associated genes (LRP5, RUNX2, COL1A1) and of genes involved in osteoclastogenesis (CSF1, PTH1R), but most notably of genes coding for inhibitors of WNT and BMP signaling, such as Sclerostin and MAB21L2. These candidate genes indicate intrinsic deficiencies in self-renewal and differentiation potential in osteoporotic stem cells. We also compared both hMSC-OP and non-osteoporotic hMSC-old of elderly donors to hMSC of ∼30 years younger donors and found that the transcriptional changes acquired between the sixth and the ninth decade of life differed widely between osteoporotic and non-osteoporotic stem cells. In addition, we compared the osteoporotic transcriptome to long term-cultivated, senescent hMSC and detected some signs for pre-senescence in hMSC-OP. Our results suggest that in primary osteoporosis the transcriptomes of hMSC populations show distinct signatures and little overlap with non-osteoporotic aging, although we detected some hints for senescence-associated changes. While there are remarkable inter-individual variations as expected for polygenetic diseases, we could identify many susceptibility genes for osteoporosis known from genetic studies. We also found new candidates, e.g. MAB21L2, a novel repressor of BMP-induced transcription. Such transcriptional changes may reflect epigenetic changes, which are part of a specific osteoporosis-associated aging process. PMID:23028809

Modeling human endothelial cell transformation in vascular neoplasias

PubMed Central

Wen, Victoria W.; MacKenzie, Karen L.

2013-01-01

Endothelial cell (EC)-derived neoplasias range from benign hemangioma to aggressive metastatic angiosarcoma, which responds poorly to current treatments and has a very high mortality rate. The development of treatments that are more effective for these disorders will be expedited by insight into the processes that promote abnormal proliferation and malignant transformation of human ECs. The study of primary endothelial malignancy has been limited by the rarity of the disease; however, there is potential for carefully characterized EC lines and animal models to play a central role in the discovery, development and testing of molecular targeted therapies for vascular neoplasias. This review describes molecular alterations that have been identified in EC-derived neoplasias, as well as the processes that underpin the immortalization and tumorigenic conversion of ECs. Human EC lines, established through the introduction of defined genetic elements or by culture of primary tumor tissue, are catalogued and discussed in relation to their relevance as models of vascular neoplasia. PMID:24046386

Team composition and chronic disease management within primary healthcare practices in eastern Ontario: an application of the Measuring Organizational Attributes of Primary Health Care Survey.

PubMed

Lukewich, Julia; Edge, Dana S; VanDenKerkhof, Elizabeth; Williamson, Tyler; Tranmer, Joan

2018-04-15

Various organizational-level attributes are being implemented in primary healthcare to improve healthcare delivery. There is a need to describe the distribution and nature of these attributes and explore differences across practices.AimThe aim of this study was to better understand organizational attributes of primary care teams, focusing specifically on team composition, nursing roles, and strategies that support chronic disease management. We employed a cross-sectional survey design. Team composition, nursing roles, availability of health services, and chronic disease management activities were described using the 'Measuring Organizational Attributes of Primary Health Care Survey.'FindingsA total of 76% (n=26 out of 34) of practice locations completed the survey, including family health teams (FHT; n=21) and community health centers (CHC; n=4). Nurse practitioners (NPs) and registered nurses (RNs) were the most common non-physician providers, and CHCs had a greater proportion of non-physician providers than FHTs. There was overlap in roles performed by NPs and RNs, and registered practical nurses engaged in fewer roles compared with NPs and RNs. A greater proportion of FHTs had systematic chronic disease management services for hypertension, depression and Alzheimer's disease compared with CHC practices. The 'Measuring Organizational Attributes of Primary Health Care Survey' was a useful tool to highlight variability in organizational attributes across PHC practices. Nurses are prominent within PHC practices, engaging in a wide range of roles related to chronic disease management, suggesting a need to better understand their contributions to patient care to optimize their roles.

Role for limited neck exploration in young adults with apparently sporadic primary hyperparathyroidism.

PubMed

Adam, Laura A; Smith, Brian J; Calva-Cerqueira, Daniel; Howe, James R; Lal, Geeta

2008-07-01

The risk of multiglandular disease (MGD) dictates the extent of exploration in patients with primary hyperparathyroidism (PHPT). Historically, young patients with PHPT were more likely to have MGD, but the existing literature is sparse and conflicting. We hypothesized that young adults (ages 16-40 years) without familial PHPT have a disease process similar to that in older patients. A 22-year retrospective chart review was performed on patients who underwent neck exploration for PHPT at our tertiary care center. Altogether, 708 charts were reviewed for demographics, family history, laboratory values, operative findings, pathology, and outcomes. As a group, young adults comprised 14.0% of the total population and were more likely to have preexisting familial disorders of PHPT (p < 0.01), therapeutic failure (p < 0.01), failure to identify an abnormal parathyroid at operation (p < 0.01), and higher reoperative rates (p = 0.02); they were less likely to have single-gland disease (p = 0.04). Young adults without a family history of the disease demonstrated no disease differences except for a higher rate of symptoms (p < 0.01). Additional analysis found that patients with a family history of hypercalcemia, a sole family member with PHPT, or nephrolithiasis ("possible" family history) were more likely to have MGD (relative risk 2.0). In this largest single-institution study of young adults with sporadic PHPT, we conclude that sporadic PHPT in young adults represents a disease entity similar to that in older patients, with no increased risk for MGD, and hence they can be managed with a similar surgical approach. Further studies are needed to assess the role of a "possible" family history as a risk factor for MGD.

Presymptomatic and longitudinal neuroimaging in neurodegeneration--from snapshots to motion picture: a systematic review.

PubMed

Schuster, Christina; Elamin, Marwa; Hardiman, Orla; Bede, Peter

2015-10-01

Recent quantitative neuroimaging studies have been successful in capturing phenotype and genotype-specific changes in dementia syndromes, amyotrophic lateral sclerosis, Parkinson's disease and other neurodegenerative conditions. However, the majority of imaging studies are cross-sectional, despite the obvious superiority of longitudinal study designs in characterising disease trajectories, response to therapy, progression rates and evaluating the presymptomatic phase of neurodegenerative conditions. The aim of this work is to perform a systematic review of longitudinal imaging initiatives in neurodegeneration focusing on methodology, optimal statistical models, follow-up intervals, attrition rates, primary study outcomes and presymptomatic studies. Longitudinal imaging studies were identified from 'PubMed' and reviewed from 1990 to 2014. The search terms 'longitudinal', 'MRI', 'presymptomatic' and 'imaging' were utilised in combination with one of the following degenerative conditions; Alzheimer's disease, amyotrophic lateral sclerosis/motor neuron disease, frontotemporal dementia, Huntington's disease, multiple sclerosis, Parkinson's disease, ataxia, HIV, alcohol abuse/dependence. A total of 423 longitudinal imaging papers and 103 genotype-based presymptomatic studies were identified and systematically reviewed. Imaging techniques, follow-up intervals and attrition rates showed significant variation depending on the primary diagnosis. Commonly used statistical models included analysis of annualised percentage change, mixed and random effect models, and non-linear cumulative models with acceleration-deceleration components. Although longitudinal imaging studies have the potential to provide crucial insights into the presymptomatic phase and natural trajectory of neurodegenerative processes a standardised design is required to enable meaningful data interpretation. 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.

Labor characteristics and program costs of a successful diabetes disease management program.

PubMed

Rothman, Russell L; So, Stephanie A; Shin, John; Malone, Robert M; Bryant, Betsy; Dewalt, Darren A; Pignone, Michael P; Dittus, Robert S

2006-05-01

Organizations have invested in disease management programs to improve quality and to reduce costs, but little is known about the labor characteristics and the program costs necessary to implement a program. To examine the labor characteristics and the program costs of a successful diabetes disease management program. We performed a labor and cost analysis within a randomized controlled trial of a primary care-based diabetes disease management intervention. Participants included 217 patients with type 2 diabetes mellitus and poor glycemic control (glycosylated hemoglobin levels, > or = 8.0%). The intervention group received 12 months of intensive management from clinical pharmacists and a diabetes care coordinator who provided education, applied algorithms for medication management, and addressed barriers to care. The control group attended a single session led by pharmacists, followed by usual care from their primary providers. The process outcomes included the number of patient care-related activities, time spent per patient, and number of drug titrations or additions. The program costs were calculated based on Bureau of Labor Statistics wage data using a sensitivity analysis. The disease management team performed a mean of 4.0 care-related activities for a mean of 38.6 minutes per patient per month for intervention patients and performed a mean of 1.1 care-related activities for a mean of 10.7 minutes per patient per month for control patients (P < .001). Intervention patients had a median of 7 drug titrations or additions during the study. The incremental program cost for the intervention was 36.97 dollars (sensitivity analysis, 6.22 dollars-88.56 dollars) per patient per month. A successful diabetes disease management program can be integrated into an academic clinic for modest labor and cost.

Motility Disorders in Children.

PubMed

Nurko, Samuel

2017-06-01

Gastrointestinal motility disorders in the pediatric population are common and can range from benign processes to more serious disorders. Performing and interpreting motility evaluations in children present unique challenges. There are primary motility disorders but abnormal motility may be secondary due to other disease processes. Diagnostic studies include radiographic scintigraphic and manometry studies. Although recent advances in the genetics, biology, and technical aspects are having an important impact and have allowed for a better understanding of the pathophysiology and therapy for gastrointestinal motility disorders in children, further research is needed to be done to have better understanding of the pathophysiology and for better therapies. Copyright © 2017 Elsevier Inc. All rights reserved.

Primary hyperparathyroidism may masquerade as rickets-osteomalacia in vitamin D replete children.

PubMed

Ganie, Mohd Ashraf; Raizada, Nishant; Chawla, Himika; Singh, Arun Kumar; Aggarwala, Sandeep; Bal, Chandra Sekhar

2016-10-01

Primary hyperparathyroidism, typically a disease of the middle aged and the old, is less commonly seen in children. In children the disease has a bimodal age distribution with calcium sensing receptor mutation presenting in infancy as hypercalcemic crises and parathyroid adenoma or hyperplasia presenting later in childhood with bone disease. The childhood parathyroid adenomas are often familial with multiglandular disease and manifest with severe bone disease unlike adults. We report a series of four male patients with juvenile primary hyperparathyroidism, three of whom presented with bone disease masquerading as rickets-osteomalacia. One patient had asymptomatic hypercalcemia with short stature. Parathyroid adenoma was detected in all the four cases and all of them underwent resection of parathyroid adenomas confirmed on histopathology. Post-surgery all the cases had initial hypocalcaemia followed by normocalcemia. One case developed pancreatitis after surgery even after achieving normocalcemia. We conclude that parathyroid adenomas, although uncommon in children, are an important cause of skeletal disease that may initially be confused with hypovitaminosis D.

Medical treatment of primary biliary cirrhosis and primary sclerosing cholangitis.

PubMed

Holtmeier, J; Leuschner, U

2001-01-01

Treatment of primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC) with ursodeoxycholic acid (UDCA) has been in common use since 1985. In PBC, treatment with UDCA improves laboratory data, liver histology, enables a longer transplantation-free interval and prolongs disease survival. Because UDCA is unable to cure the disease newer drugs or combination therapies are still needed. Studies with UDCA and immunosuppressants such as prednisone, budesonide and azathioprine have shown that in selected patients combination therapy may be superior to UDCA monotherapy. PSC is treated successfully with UDCA and endoscopic dilatation of the bile duct strictures. Treatment of extrahepatic manifestations of cholestatic liver disease such as pruritus, fatigue, osteoporosis and steatorrhea can be problematic and time-consuming. Copyright 2001 S. Karger AG, Basel

Primary Prevention of Congenital Anomalies: Special Focus on Environmental Chemicals and other Toxicants, Maternal Health and Health Services and Infectious Diseases.

PubMed

Taruscio, Domenica; Baldi, Francesca; Carbone, Pietro; Neville, Amanda J; Rezza, Giovanni; Rizzo, Caterina; Mantovani, Alberto

2017-01-01

Congenital anomalies (CA) represent an important fraction of rare diseases, due to the critical role of non-genetic factors in their pathogenesis. CA are the main group of rare diseases in which primary prevention measures will have a beneficial impact. Indeed, since 2013 the European Union has endorsed a body of evidence-based recommendations for CA primary prevention; the recommendations aim at facilitating the inclusion of primary prevention actions the National Rare Disease Plans of EU Member States and encompass different public health fields, from environment through to maternal diseases and lifestyles.The chapter overviews and discusses the assessment of main risk factors for CA, such as environmental toxicants, maternal health and lifestyles and infections, with a special attention to issues that are emerging or need more knowledge.Overall, the availability of CA registries is important for estimating the health burden of CA, identifying possible hotspots, assessing the impact of interventions and addressing further, fit-to-purpose research.The integration of relevant public health actions that are already in place (e.g., control of noxious chemicals, vaccination programmes, public health services addressing chronic maternal conditions) can increase the affordability and sustainability of CA primary prevention. In developing countries with less primary prevention in place and limited overall resources, a first recognition phase may be pivotal in order to identify priority targets. In the meanwhile, policy makers should be made aware that primary prevention of RD supports publicly endorsed societal values like the knowledge-based promotion of health, empowerment, equity and social inclusiveness.

Graves' disease associated with infectious mononucleosis due to primary Epstein-Barr virus infection: report of 3 cases.

PubMed

Akahori, Hiroshi; Takeshita, Yumie; Saito, Reina; Kaneko, Shuichi; Takamura, Toshinari

2010-01-01

Although the etiology of Graves' disease is still not clear, it is generally suggested that environmental factors such as infections contribute to the development of Graves' disease. We report here three cases of Graves' disease which presented simultaneously with infectious mononucleosis due to primary EBV infection. Acute EBV infection might play an important role in the onset of Graves' disease. These three women complained of a sore throat or neck pain, resembling subacute thyroiditis. In the case of thyrotoxicosis accompanied by sore throat or neck pain, Graves' disease must be distinguished from subacute thyroiditis.

EULAR Sjögren's syndrome disease activity index (ESSDAI): a user guide

PubMed Central

Seror, Raphaèle; Bowman, Simon J; Brito-Zeron, Pilar; Theander, Elke; Bootsma, Hendrika; Tzioufas, Athanasios; Gottenberg, Jacques-Eric; Ramos-Casals, Manel; Dörner, Thomas; Ravaud, Philippe; Vitali, Claudio; Mariette, Xavier

2015-01-01

The EULAR Sjögren's syndrome (SS) disease activity index (ESSDAI) is a systemic disease activity index that was designed to measure disease activity in patients with primary SS. With the growing use of the ESSDAI, some domains appear to be more challenging to rate than others. The ESSDAI is now in use as a gold standard to measure disease activity in clinical studies, and as an outcome measure, even a primary outcome measure, in current randomised clinical trials. Therefore, ensuring an accurate and reproducible rating of each domain, by providing a more detailed definition of each domain, has emerged as an urgent need. The purpose of the present article is to provide a user guide for the ESSDAI. This guide provides definitions and precisions on the rating of each domain. It also includes some minor improvement of the score to integrate advance in knowledge of disease manifestations. This user guide may help clinicians to use the ESSDAI, and increase the reliability of rating and consequently of the ability to detect true changes over time. This better appraisal of ESSDAI items, along with the recent definition of disease activity levels and minimal clinically important change, will improve the assessment of patients with primary SS and facilitate the demonstration of effectiveness of treatment for patients with primary SS. PMID:26509054

Cognitive Function, Coping, and Depressive Symptoms in Children and Adolescents with Sickle Cell Disease.

PubMed

Prussien, Kemar V; DeBaun, Michael R; Yarboi, Janet; Bemis, Heather; McNally, Colleen; Williams, Ellen; Compas, Bruce E

2018-06-01

The objective of this study was to investigate the association between cognitive functioning, coping, and depressive symptoms in children and adolescents with sickle cell disease (SCD). Forty-four children (M age = 9.30, SD = 3.08; 56.8% male) with SCD completed cognitive assessments measuring working memory (Wechsler Intelligence Scale for Children-Fourth Edition) and verbal comprehension (Wechsler Abbreviated Scale of Intelligence-Second Edition). Participants' primary caregivers completed questionnaires assessing their child's coping and depressive symptoms. Verbal comprehension was significantly positively associated with secondary control coping (cognitive reappraisal, acceptance, distraction), and both working memory and secondary control coping were negatively associated with depressive symptoms. In partial support of the primary study hypothesis, verbal comprehension had an indirect association with depressive symptoms through secondary control coping, whereas working memory had a direct association with depressive symptoms. The results provide new evidence for the associations between cognitive function and coping, and the association of both of these processes with depressive symptoms in children with SCD. Findings provide potential implications for clinical practice, including interventions to improve children's cognitive functioning to attenuate depressive symptoms.

Health system challenges of NCDs in Tunisia.

PubMed

Ben Romdhane, Habiba; Tlili, Faten; Skhiri, Afef; Zaman, Shahaduz; Phillimore, Peter

2015-01-01

The objective of this study was to present a qualitative 'situation analysis' of the healthcare system in Tunisia, as it applies to management of cardiovascular disease (CVD) and diabetes. A primary concern was the institutional capacity to manage non-communicable diseases (NCDs). Research took place during 2010 (analysis of official documents, semi-structured interviews with key informants, and case studies in four clinics). Walt and Gilson's framework (1994) for policy analysis was used: content, actors, context, and process. Problems of integration and coordination have compounded funding pressures. Despite its importance in Tunisian healthcare, primary health is ill-equipped to manage NCDs. With limited funds, and no referral or health information system, staff morale in the public sector was low. Private healthcare has been the main development filling the void. This study highlights major gaps in the implementation of a comprehensive approach to NCDs, which is an urgent task across the region. In strategic planning, research on the health system is vital; but the capacity within Ministries of Health to use research has first to be built, with a commitment to grounding policy change in evidence.

Primary Sclerosing Cholangitis

MedlinePlus

... Grants & Grant History Research Resources Research at NIDDK Technology Advancement & Transfer Meetings & Workshops Health Information Diabetes Digestive Diseases Kidney Disease Weight Management Liver Disease Urologic Diseases Endocrine Diseases Diet & Nutrition ...

Identification, summary and comparison of tools used to measure organizational attributes associated with chronic disease management within primary care settings

PubMed Central

Lukewich, Julia; Corbin, Renée; VanDenKerkhof, Elizabeth G; Edge, Dana S; Williamson, Tyler; Tranmer, Joan E

2014-01-01

Rationale, aims and objectives Given the increasing emphasis being placed on managing patients with chronic diseases within primary care, there is a need to better understand which primary care organizational attributes affect the quality of care that patients with chronic diseases receive. This study aimed to identify, summarize and compare data collection tools that describe and measure organizational attributes used within the primary care setting worldwide. Methods Systematic search and review methodology consisting of a comprehensive and exhaustive search that is based on a broad question to identify the best available evidence was employed. Results A total of 30 organizational attribute data collection tools that have been used within the primary care setting were identified. The tools varied with respect to overall focus and level of organizational detail captured, theoretical foundations, administration and completion methods, types of questions asked, and the extent to which psychometric property testing had been performed. The tools utilized within the Quality and Costs of Primary Care in Europe study and the Canadian Primary Health Care Practice-Based Surveys were the most recently developed tools. Furthermore, of the 30 tools reviewed, the Canadian Primary Health Care Practice-Based Surveys collected the most information on organizational attributes. Conclusions There is a need to collect primary care organizational attribute information at a national level to better understand factors affecting the quality of chronic disease prevention and management across a given country. The data collection tools identified in this review can be used to establish data collection strategies to collect this important information. PMID:24840066

Primary Biliary Cholangitis: advances in management and treatment of the disease.

PubMed

Invernizzi, Pietro; Floreani, Annarosa; Carbone, Marco; Marzioni, Marco; Craxi, Antonio; Muratori, Luigi; Vespasiani Gentilucci, Umberto; Gardini, Ivan; Gasbarrini, Antonio; Kruger, Paola; Mennini, Francesco Saverio; Ronco, Virginia; Lanati, Elena; Canonico, Pier Luigi; Alvaro, Domenico

2017-08-01

Primary Biliary Cholangitis, previously known as Primary Biliary Cirrhosis, is a rare disease, which mainly affects women in their fifth to seventh decades of life. It is a chronic autoimmune disease characterized by a progressive damage of interlobular bile ducts leading to ductopenia, chronic cholestasis and bile acids retention. Even if the disease usually presents a long asymptomatic phase and a slow progression, in many patients it may progress faster toward cirrhosis and its complications. The 10year mortality is greater than in diseases such as human immunodeficiency virus/Hepatitis C Virus coinfection and breast cancer. Ursodeoxycholic acid is the only treatment available today, but even if effective in counteracting the disease progression for the majority of patients, in approximately 40% is not able to decrease effectively the alkaline phosphatase, a surrogate marker of disease activity. Recently, obeticholic acid received the European Medicines Agency conditional approval, as add on treatment in patients non responders or intolerant to ursodeoxycholic acid. The present paper illustrates the opinion of a working group, composed by clinical pharmacologists, gastroenterologists/hepatologists with specific expertise on Primary Biliary Cholangitis and patient associations, on the state of the art and future perspectives of the disease management. The agreement on the document was reached through an Expert Meeting. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Mad dogs, vampires, and zombie ants: a multidisciplinary approach to teaching neuroscience, behavior, and microbiology.

PubMed

Esteban, David J; Holloway, Kevin S

2015-01-01

Viruses, parasites, and some bacteria use host organisms to complete their lifecycle. These infectious agents are able to hijack host processes to replicate and transmit to the next host. While we tend to think of infections as just making us sick, they are also capable of changing host behavior. In fact, many infectious agents are able to mediate host behavior in ways that can enhance transmission of the disease. In this course we explore the process of host behavior mediation by infectious agents, combining aspects of multiple fields including neurobiology, animal behavior, infectious disease microbiology, and epidemiology. The goals for this course are: 1) To explore the neurological and behavioral effects of infectious organisms on their hosts, in particular pathogen mediation of host behavior to the benefit of the pathogen, 2) to introduce students to primary literature in a multidisciplinary field, and 3) when applicable, to address cultural/historical/mythological perspectives that might alter societal norms and pressures and influence the impact of the biological processes of behavior modification by infections.

Mad Dogs, Vampires, and Zombie Ants: A Multidisciplinary Approach to Teaching Neuroscience, Behavior, and Microbiology

PubMed Central

Esteban, David J.; Holloway, Kevin S.

2015-01-01

Viruses, parasites, and some bacteria use host organisms to complete their lifecycle. These infectious agents are able to hijack host processes to replicate and transmit to the next host. While we tend to think of infections as just making us sick, they are also capable of changing host behavior. In fact, many infectious agents are able to mediate host behavior in ways that can enhance transmission of the disease. In this course we explore the process of host behavior mediation by infectious agents, combining aspects of multiple fields including neurobiology, animal behavior, infectious disease microbiology, and epidemiology. The goals for this course are: 1) To explore the neurological and behavioral effects of infectious organisms on their hosts, in particular pathogen mediation of host behavior to the benefit of the pathogen, 2) to introduce students to primary literature in a multidisciplinary field, and 3) when applicable, to address cultural/historical/mythological perspectives that might alter societal norms and pressures and influence the impact of the biological processes of behavior modification by infections. PMID:25838806

Tick-borne infections in human and animal population worldwide

PubMed Central

Brites-Neto, José; Duarte, Keila Maria Roncato; Martins, Thiago Fernandes

2015-01-01

The abundance and activity of ectoparasites and its hosts are affected by various abiotic factors, such as climate and other organisms (predators, pathogens and competitors) presenting thus multiples forms of association (obligate to facultative, permanent to intermittent and superficial to subcutaneous) developed during long co-evolving processes. Ticks are ectoparasites widespread globally and its eco epidemiology are closely related to the environmental conditions. They are obligatory hematophagous ectoparasites and responsible as vectors or reservoirs at the transmission of pathogenic fungi, protozoa, viruses, rickettsia and others bacteria during their feeding process on the hosts. Ticks constitute the second vector group that transmit the major number of pathogens to humans and play a role primary for animals in the process of diseases transmission. Many studies on bioecology of ticks, considering the information related to their population dynamics, to the host and the environment, comes possible the application and efficiency of tick control measures in the prevention programs of vector-borne diseases. In this review were considered some taxonomic, morphological, epidemiological and clinical fundamental aspects related to the tick-borne infections that affect human and animal populations. PMID:27047089

Abnormalities of peptide metabolism in Alzheimer disease.

PubMed

Panchal, Maï; Rholam, Mohamed; Brakch, Noureddine

2004-10-01

The steady-state level of peptide hormones represents a balance between their biosynthesis and proteolytic processing by convertases and their catabolism by proteolytic enzymes. Low levels of neuropeptide Y, somatostatin and corticotropin-releasing factor, described in Alzheimer disease (AD), were related to a defect in proteolytic processing of their protein precursors. In contrast the abundance of beta-amyloid peptides, the major protein constituents of senile plaques is likely related to inefficient catabolism. Therefore, attention is mainly focused on convertases that generate active peptides and counter-regulatory proteases that are involved in their catabolism. Some well-described proteases such as NEP are thought to be involved in beta-amyloid catabolism. The search of other possible candidates represents a primary effort in the field. A variety of vascular risk factors such as diabetes, hypertension and arteriosclerosis suggest that the functional vascular defect contributes to AD pathology. It has also been described that beta-amyloid peptides potentiate endothelin-1 induced vasoconstriction. In this review, we will critically evaluate evidence relating proteases implicated in amyloid protein precursor proteolytic processing and beta-amyloid catabolism.

Immunocytochemical investigation of immune cells within human primary and permanent tooth pulp.

PubMed

Rodd, H D; Boissonade, F M

2006-01-01

The aim of this study was to determine whether there are any differences in the number and distribution of immune cells within human primary and permanent tooth pulp, both in health and disease. The research took the form of a quantitative immunocytochemical study. One hundred and twenty-four mandibular first permanent molars and second primary molars were obtained from children requiring dental extractions under general anaesthesia. Following exodontia, 10-microm-thick frozen pulp sections were processed for indirect immunofluorescence. Triple-labelling regimes were employed using combinations of the following: (1) protein gene product 9.5, a general neuronal marker; (2) leucocyte common antigen (LCA); and (3) Ulex europaeus I lectin, a marker of vascular endothelium. Image analysis was then used to determine the percentage area of immunostaining for LCA. Leucocytes were significantly more abundant in the pulp horn and mid-coronal region of intact and carious primary teeth, as compared to permanent teeth (P < 0.05, anova). Both dentitions demonstrated the presence of well-localized inflammatory cell infiltrates and marked aborization of pulpal nerves in areas of dense leucocyte accumulation. Primary and permanent tooth pulps appear to have a similar potential to mount inflammatory responses to gross caries The management of the compromised primary tooth pulp needs to be reappraised in the light of these findings.

PRIMARY CILIARY DYSKINESIA: DIAGNOSTIC AND PHENOTYPIC FEATURES

EPA Science Inventory

Primary ciliary dyskinesia (PCD) is a genetic disease characterized by abnormalities in ciliary structure/function. We hypothesized that the major clinical and biologic phenotypic markers of the disease could be evaluated by studying a cohort of subjects suspected of having PCD. ...

What is the best strategy for investigating abnormal liver function tests in primary care? Implications from a prospective study.

PubMed

Lilford, Richard J; Bentham, Louise M; Armstrong, Matthew J; Neuberger, James; Girling, Alan J

2013-06-20

Evaluation of predictive value of liver function tests (LFTs) for the detection of liver-related disease in primary care. A prospective observational study. 11 UK primary care practices. Patients (n=1290) with an abnormal eight-panel LFT (but no previously diagnosed liver disease). Patients were investigated by recording clinical features, and repeating LFTs, specific tests for individual liver diseases, and abdominal ultrasound scan. Patients were characterised as having: hepatocellular disease; biliary disease; tumours of the hepato-biliary system and none of the above. The relationship between LFT results and disease categories was evaluated by stepwise regression and logistic discrimination, with adjustment for demographic and clinical factors. True and False Positives generated by all possible LFT combinations were compared with a view towards optimising the choice of analytes in the routine LFT panel. Regression methods showed that alanine aminotransferase (ALT) was associated with hepatocellular disease (32 patients), while alkaline phosphatase (ALP) was associated with biliary disease (12 patients) and tumours of the hepatobiliary system (9 patients). A restricted panel of ALT and ALP was an efficient choice of analytes, comparing favourably with the complete panel of eight analytes, provided that 48 False Positives can be tolerated to obtain one additional True Positive. Repeating a complete panel in response to an abnormal reading is not the optimal strategy. The LFT panel can be restricted to ALT and ALP when the purpose of testing is to exclude liver disease in primary care.

Impact of Antithrombotic Therapy in Atrial Fibrillation on the Presentation of Coronary Artery Disease

PubMed Central

Chan, Pak Hei; Li, Wen Hua; Hai, Jo Jo; Tse, Hung Fat; Siu, Chung Wah

2015-01-01

Background Little is known about whether atrial fibrillation is a presentation of coronary disease. There is a paucity of knowledge about their causal relationship and also the impact of different antithrombotic strategies on the subsequent presentation of symptomatic coronary disease. Methods and Results We studied 7,526 Chinese patients diagnosed with non-valvular atrial fibrillation and no documented history of coronary artery disease. The primary endpoint was the new occurrence of coronary artery disease—either stable coronary artery disease or acute coronary syndrome. After a mean follow-up of 3.2±3.5 years (24,071 patient-years), a primary endpoint occurred in 987 patients (13.1%). The overall annual incidence of coronary artery disease was 4.10%/year. No significant differences in age, sex, and mean CHA2DS2-VASc score were observed between patients with and without the primary endpoint. When stratified according to the antithrombotic strategies applied for stroke prevention, the annual incidence of coronary artery disease was 5.49%/year, 4.45%/year and 2.16%/year respectively in those prescribed no antithrombotic therapy, aspirin, and warfarin. Similar trends were observed in patients with acute coronary syndromes. Diabetes mellitus, smoking history and renal failure requiring dialysis were predictors for primary endpoint in all antithrombotic therapies. Conclusion In patients with non-valvular atrial fibrillation, there is a modest association with coronary artery disease. Patients prescribed warfarin had the lowest risk of new onset coronary artery disease. PMID:26098876

A randomised controlled trial of a consumer-focused e-health strategy for cardiovascular risk management in primary care: the Consumer Navigation of Electronic Cardiovascular Tools (CONNECT) study protocol.

PubMed

Redfern, Julie; Usherwood, T; Harris, M F; Rodgers, A; Hayman, N; Panaretto, K; Chow, C; Lau, A Y S; Neubeck, L; Coorey, G; Hersch, F; Heeley, E; Patel, A; Jan, S; Zwar, N; Peiris, D

2014-01-31

Fewer than half of all people at highest risk of a cardiovascular event are receiving and adhering to best practice recommendations to lower their risk. In this project, we examine the role of an e-health-assisted consumer-focused strategy as a means of overcoming these gaps between evidence and practice. Consumer Navigation of Electronic Cardiovascular Tools (CONNECT) aims to test whether a consumer-focused e-health strategy provided to Aboriginal and Torres Strait Islander and non-indigenous adults, recruited through primary care, at moderate-to-high risk of a cardiovascular disease event will improve risk factor control when compared with usual care. Randomised controlled trial of 2000 participants with an average of 18 months of follow-up to evaluate the effectiveness of an integrated consumer-directed e-health portal on cardiovascular risk compared with usual care in patients with cardiovascular disease or who are at moderate-to-high cardiovascular disease risk. The trial will be augmented by formal economic and process evaluations to assess acceptability, equity and cost-effectiveness of the intervention. The intervention group will participate in a consumer-directed e-health strategy for cardiovascular risk management. The programme is electronically integrated with the primary care provider's software and will include interactive smart phone and Internet platforms. The primary outcome is a composite endpoint of the proportion of people meeting the Australian guideline-recommended blood pressure (BP) and cholesterol targets. Secondary outcomes include change in mean BP and fasting cholesterol levels, proportion meeting BP and cholesterol targets separately, self-efficacy, health literacy, self-reported point prevalence abstinence in smoking, body mass index and waist circumference, self-reported physical activity and self-reported medication adherence. Primary ethics approval was received from the University of Sydney Human Research Ethics Committee and the Aboriginal Health and Medical Research Council. Results will be disseminated via the usual scientific forums including peer-reviewed publications and presentations at international conferences ACTRN12613000715774.

Genomic analysis of Fusarium verticillioides.

PubMed

Brown, D W; Butchko, R A E; Proctor, R H

2008-09-01

Fusarium verticillioides (teleomorph Gibberella moniliformis) can be either an endophyte of maize, causing no visible disease, or a pathogen-causing disease of ears, stalks, roots and seedlings. At any stage, this fungus can synthesize fumonisins, a family of mycotoxins structurally similar to the sphingolipid sphinganine. Ingestion of fumonisin-contaminated maize has been associated with a number of animal diseases, including cancer in rodents, and exposure has been correlated with human oesophageal cancer in some regions of the world, and some evidence suggests that fumonisins are a risk factor for neural tube defects. A primary goal of the authors' laboratory is to eliminate fumonisin contamination of maize and maize products. Understanding how and why these toxins are made and the F. verticillioides-maize disease process will allow one to develop novel strategies to limit tissue destruction (rot) and fumonisin production. To meet this goal, genomic sequence data, expressed sequence tags (ESTs) and microarrays are being used to identify F. verticillioides genes involved in the biosynthesis of toxins and plant pathogenesis. This paper describes the current status of F. verticillioides genomic resources and three approaches being used to mine microarray data from a wild-type strain cultured in liquid fumonisin production medium for 12, 24, 48, 72, 96 and 120h. Taken together, these approaches demonstrate the power of microarray technology to provide information on different biological processes.

Identification of luminal breast cancers that establish a tumor-supportive macroenvironment defined by proangiogenic platelets and bone marrow-derived cells.

PubMed

Kuznetsov, Hanna S; Marsh, Timothy; Markens, Beth A; Castaño, Zafira; Greene-Colozzi, April; Hay, Samantha A; Brown, Victoria E; Richardson, Andrea L; Signoretti, Sabina; Battinelli, Elisabeth M; McAllister, Sandra S

2012-12-01

Breast cancer recurrence rates vary following treatment, suggesting that tumor cells disseminate early from primary sites but remain indolent indefinitely before progressing to symptomatic disease. The reasons why some indolent disseminated tumors erupt into overt disease are unknown. We discovered a novel process by which certain luminal breast cancer (LBC) cells and patient tumor specimens (LBC "instigators") establish a systemic macroenvironment that supports outgrowth of otherwise-indolent disseminated tumors ("responders"). Instigating LBCs secrete cytokines that are absorbed by platelets, which are recruited to responding tumor sites where they aid vessel formation. Instigator-activated bone marrow cells enrich responding tumor cell expression of CD24, an adhesion molecule for platelets, and provide a source of VEGF receptor 2(+) tumor vessel cells. This cascade results in growth of responder adenocarcinomas and is abolished when platelet activation is inhibited by aspirin. These findings highlight the macroenvironment as an important component of disease progression that can be exploited therapeutically. Currently, processes that mediate progression of otherwise indolent tumors are not well understood, making it difficult to accurately predict which cancer patients are likely to relapse. Our findings highlight the macroenvironment as an important component of disease progression that can be exploited to more accurately identify patients who would benefit from adjuvant therapy. ©2012 AACR.

Circadian rhythms, Wnt/beta-catenin pathway and PPAR alpha/gamma profiles in diseases with primary or secondary cardiac dysfunction

PubMed Central

Lecarpentier, Yves; Claes, Victor; Duthoit, Guillaume; Hébert, Jean-Louis

2014-01-01

Circadian clock mechanisms are far-from-equilibrium dissipative structures. Peroxisome proliferator-activated receptors (PPAR alpha, beta/delta, and gamma) play a key role in metabolic regulatory processes, particularly in heart muscle. Links between circadian rhythms (CRs) and PPARs have been established. Mammalian CRs involve at least two critical transcription factors, CLOCK and BMAL1 (Gekakis et al., 1998; Hogenesch et al., 1998). PPAR gamma plays a major role in both glucose and lipid metabolisms and presents circadian properties which coordinate the interplay between metabolism and CRs. PPAR gamma is a major component of the vascular clock. Vascular PPAR gamma is a peripheral regulator of cardiovascular rhythms controlling circadian variations in blood pressure and heart rate through BMAL1. We focused our review on diseases with abnormalities of CRs and with primary or secondary cardiac dysfunction. Moreover, these diseases presented changes in the Wnt/beta-catenin pathway and PPARs, according to two opposed profiles. Profile 1 was defined as follows: inactivation of the Wnt/beta-catenin pathway with increased expression of PPAR gamma. Profile 2 was defined as follows: activation of the Wnt/beta-catenin pathway with decreased expression of PPAR gamma. A typical profile 1 disease is arrhythmogenic right ventricular cardiomyopathy, a genetic cardiac disease which presents mutations of the desmosomal proteins and is mainly characterized by fatty acid accumulation in adult cardiomyocytes mainly in the right ventricle. The link between PPAR gamma dysfunction and desmosomal genetic mutations occurs via inactivation of the Wnt/beta-catenin pathway presenting oscillatory properties. A typical profile 2 disease is type 2 diabetes, with activation of the Wnt/beta-catenin pathway and decreased expression of PPAR gamma. CRs abnormalities are present in numerous pathologies such as cardiovascular diseases, sympathetic/parasympathetic dysfunction, hypertension, diabetes, neurodegenerative diseases, cancer which are often closely inter-related. PMID:25414671

Long-term oxygen therapy in Japan: history, present status, and current problems.

PubMed

Kida, Kozui; Motegi, Takashi; Ishii, Takeo; Hattori, Kumiko

2013-01-01

Historically, the progress of long term-oxygen therapy (LTOT) in Japan has been characterized by collaboration among academic groups, policy makers, and industrial companies. The public health insurance program has covered the cost of LTOT since 1985. Thomas Petty's group in Denver enthusiastically carried out the public implementation of LTOT and conveyed the concept of pulmonary rehabilitation for the processing with LTOT. Although the target diseases of LTOT in Japan tended to be chronic obstructive pulmonary disease or sequelae of primary lung tuberculosis, it was soon applied for cardiac diseases as well as other pulmonary diseases. Together with increasing medical costs for geriatric patients, the political conversion from hospital based care of a traditional style to home care system has been performed, with two background reasons: the improvement of quality of life of patients and the reduction of the medical expense. Presently, LTOT plays a pivotal role in the successful implementation of home respiratory care for elderly patients. In addition, this promotes comprehensive pulmonary rehabilitation, a team approach, and close liaisons between primary care and hospitals. Currently, the total number of patients using LTOT exceeds 150,000. In Japan, LTOT resulted in an advancement in the medical care as well as in administrative decision to introduce it as a nationwide system after analyzing the results of opinion polls of patients with respiratory failure. However, the recent great earthquake in East Japan revealed that many unresolved problems remain for these patients, and these issues are of great concern.

[Liver involvement in coeliac disease].

PubMed

Riestra, S; Fernández, E; Rodrigo, L

1999-12-01

Coeliac disease is a gluten-sensitive enteropathy in which, genetic, immunologic and environmental factors are implied. Several extradigestive diseases have been described in association with coeliac disease, which share most of the times an immunologic mechanism. The liver is damaged in coeliac disease, and it has been considered by some authors as an extraintestinal manifestation of the disease. In the present revision we discuss the different hepatic diseases related with the coeliac disease, as well as the best approach to diagnosis and therapy of choice. At diagnosis, it is very frequent to find an asymptomatic hipertransaminasemia, which frequently disappears after gluten suppression; the morphological substratum found in this alteration is a non-specific reactive hepatitis in the majority of cases. Coeliac disease is a demonstrated cause of cryptogenic hipertransaminasemia. In a small percentage of patient with coeliac disease an association has been found with other immunological liver diseases, such as primary biliary cirrhosis, primary sclerosing cholangitis and autoimmune hepatitis. Few studies exist that include a large number of patient, and the results on occasions are discordant. Nevertheless, the strongest association is with autoimmune hepatitis and with primary biliary cirrhosis. Several communications of isolated cases of rare hepatic diseases, which probably, only reflect a fortuitous association, have been cited in the literature.

The effect of comorbidities upon ocular and systemic health-related quality of life.

PubMed

Real, F J; Brown, G C; Brown, H C; Brown, M M

2008-06-01

The purpose of the study was to assess whether, and to what degree, comorbidities affect patient quality of life. A cross-sectional, quality-of-life study of 170 consecutive vitreoretinal patients compared the utility associated with a participant's primary (most incapacitating) disease and the utility associated with a grouping of all of the participants' diseases. The ocular diseases present included diabetic retinopathy (44%), macular degeneration (30%), lattice degeneration/retinal tear (14%), retinal vascular obstruction (5%), uveitis, macular oedema, macular pucker (5%) and others (2%). Participants underwent interviewer-administered, time trade-off utility questions for each disease, then for a compilation of all diseases. Their primary disease was defined by the lowest utility reported for a single disease, while other health conditions were considered comorbidities. A two-tailed, paired t test was used to compare the means of the primary disease utilities and compilation utilities. The study was powered to have a 90% chance of detecting an 8% difference in mean utility between the two utility groups The mean lowest utility for the most disabling single health condition (primary disease) was 0.82 (SD 0.22; 95% CI 0.79 to 0.85. The mean utility for the grouping together of all diseases was 0.80 (SD 0.24, 95% CI 0.76 to 0.84). No significant difference was found between the mean utilities of the two groups (p = 0.56). The overall health-related quality of life of a patient in an ophthalmic population with serious diseases appears to be primarily determined by the single disease that most adversely affects the individual's quality of life. This conclusion has significant implications in clinical care and when considering the use of comorbidities in cost-utility analyses.

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

PubMed

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

2010-02-18

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

International Classification of Primary Care-2 coding of primary care data at the general out-patients' clinic of General Hospital, Lagos, Nigeria.

PubMed

Olagundoye, Olawunmi Abimbola; van Boven, Kees; van Weel, Chris

2016-01-01

Primary care serves as an integral part of the health systems of nations especially the African continent. It is the portal of entry for nearly all patients into the health care system. Paucity of accurate data for health statistics remains a challenge in the most parts of Africa because of inadequate technical manpower and infrastructure. Inadequate quality of data systems contributes to inaccurate data. A simple-to-use classification system such as the International Classification of Primary Care (ICPC) may be a solution to this problem at the primary care level. To apply ICPC-2 for secondary coding of reasons for encounter (RfE), problems managed and processes of care in a Nigerian primary care setting. Furthermore, to analyze the value of selected presented symptoms as predictors of the most common diagnoses encountered in the study setting. Content analysis of randomly selected patients' paper records for data collection at the end of clinic sessions conducted by family physicians at the general out-patients' clinics. Contents of clinical consultations were secondarily coded with the ICPC-2 and recorded into excel spreadsheets with fields for sociodemographic data such as age, sex, occupation, religion, and ICPC elements of an encounter: RfE/complaints, diagnoses/problems, and interventions/processes of care. Four hundred and one encounters considered in this study yielded 915 RfEs, 546 diagnoses, and 1221 processes. This implies an average of 2.3 RfE, 1.4 diagnoses, and 3.0 processes per encounter. The top 10 RfE, diagnoses/common illnesses, and processes were determined. Through the determination of the probability of the occurrence of certain diseases beginning with a RfE/complaint, the top five diagnoses that resulted from each of the top five RfE were also obtained. The top five RfE were: headache, fever, pain general/multiple sites, visual disturbance other and abdominal pain/cramps general. The top five diagnoses were: Malaria, hypertension uncomplicated, visual disturbance other, peptic ulcer, and upper respiratory infection. From the determination of the posterior probability given the top five RfE, malaria, hypertension, upper respiratory infection, refractive error, and conjuctivitis were the five most frequent diagnoses that resulted from a complaint of a headache. The study demonstrated that ICPC-2 can be applied to primary care data in the Nigerian context to generate information about morbidity and services provided. It also provided an empirical basis to support diagnosis and prognostication in a primary care setting. In developing countries where the transition to electronic health records is still evolving and fraught with limitations, more reliable data collection can be achieved from paper records through the application of the ICPC-2.

[Increasing participation of primary care in the management of people with human immunodeficiency virus: hospital care professionals express their views].

PubMed

Ortega López, Angela; Morales Asencio, José Miguel; Rengel Díaz, Cristóbal; Peñas Cárdenas, Eloísa María; González Rodríguez, María José; Prado de la Sierra, Rut

2014-04-01

To determine the opinions of infectious diseases professionals on the possibilities of monitoring patients with HIV in Primary Care. Qualitative study using in-depth interviews. Infectious Diseases Unit in the University Hospital "Virgen de la Victoria" in Málaga. Health professionals with more than one year experience working in infectious diseases. A total of 25 respondents: 5 doctors, 15 nurses and 5 nursing assistants. Convenience sample. Semi-structured interviews were used that were later transcribed verbatim. Content analysis was performed according to the Taylor and Bogdan approach with computer support. Validation of information was made through additional analysis, expert participation, and feedback of part of the results to the participants. Hospital care professionals considered the disease-related complexity of HIV, treatment and social aspects that may have an effect on the organizational level of care. Professionals highlighted the benefits of specialized care, although opinions differed between doctors and nurses as regards follow up in Primary Care. Some concerns emerged about the level of training, confidentiality and workload in Primary Care, although they mentioned potential advantages related to accessibility of patients. Physicians perceive difficulties in following up HIV patients in Primary Care, even for those patients with a good control of their disease. Nurses and nursing assistants are more open to this possibility due to the proximity to home and health promotion in Primary Care. Copyright © 2013 Elsevier España, S.L. All rights reserved.

Simultaneous Primary Hodgkin's Lymphoma of the Sigmoid Colon and Papillary Thyroid Carcinoma in an HIV-Positive Patient.

PubMed

Liszewski, Walter; Sittig, Mark; Kandil, Emad; Van Sickels, Nicholas; Safah, Hana

2015-01-01

Primary Hodgkin's lymphoma of the colon is a rare phenomenon previously only reported in patients with chronic diverticulitis or inflammatory bowel disease. Herein we report a case of primary Hodgkin's lymphoma of the sigmoid colon in an HIV-positive patient without a history of inflammatory bowel disease or chronic diverticulitis that was later complicated by the discovery of concurrent papillary thyroid carcinoma.

Common mutation underlying primary hyperoxaluria type1 in three Indian children

PubMed Central

Chanchlani, R.; Sinha, A.; Gulati, A.; Agarwal, V.; Bagga, A.

2012-01-01

Primary hyperoxaluria is an autosomal recessive disorder caused by deficiency of alanine-glyoxylate aminotransferase, which is encoded by the AGXT gene. We report three Indian children with primary hyperoxaluria type1 having a common mutation in this gene. All patients had evidence of chronic kidney disease at the time of diagnosis, with subsequent progression to end-stage renal disease. The detection of an identical mutation in the AGXT gene suggests that specific genetic screening for this mutation may be useful when considering the diagnosis of primary hyperoxaluria type1. PMID:23439734

Common mutation underlying primary hyperoxaluria type1 in three Indian children.

PubMed

Chanchlani, R; Sinha, A; Gulati, A; Agarwal, V; Bagga, A

2012-11-01

Primary hyperoxaluria is an autosomal recessive disorder caused by deficiency of alanine-glyoxylate aminotransferase, which is encoded by the AGXT gene. We report three Indian children with primary hyperoxaluria type1 having a common mutation in this gene. All patients had evidence of chronic kidney disease at the time of diagnosis, with subsequent progression to end-stage renal disease. The detection of an identical mutation in the AGXT gene suggests that specific genetic screening for this mutation may be useful when considering the diagnosis of primary hyperoxaluria type1.

Early Disseminated Lyme Disease Causing False-Positive Serology for Primary Epstein-Barr Virus Infection: Report of 2 Cases.

PubMed

Pavletic, Adriana J; Marques, Adriana R

2017-07-15

False-positive serology for Lyme disease was reported in patients with acute infectious mononucleosis. Here we describe 2 patients with early disseminated Lyme disease who were misdiagnosed with infectious mononucleosis based on false-positive tests for primary Epstein-Barr virus infection. Published by Oxford University Press for the Infectious Diseases Society of America 2017. This work is written by (a) US Government employee(s) and is in the public domain in the US.

Effect of steroid replacement on thyroid function and thyroid autoimmunity in Addison's disease with primary hypothyroidism

PubMed Central

Sahoo, Jaya Prakash; Selviambigapathy, Jayakumar; Kamalanathan, Sadishkumar; Nagarajan, K.; Vivekanandan, Muthupillai

2016-01-01

Background: Steroid replacement without thyroxine supplementation normalizes thyroid function test (TFT) in some but not all Addison's disease patients with primary hypothyroidism. Both autoimmune and nonautoimmune mechanisms contribute to this improvement in TFT. However, the documentation of the change in thyroid autoimmunity after cortisol replacement is very limited in the literature. The aim of this study was to determine the effect of steroid replacement on TFT and anti-thyroid peroxidase antibody (anti-TPO-Ab) titer in Addison's disease with primary hypothyroidism. Materials and Methods: This observational study was conducted in a tertiary care center in South India. Six Addison's disease patients with primary hypothyroidism, who were only on steroid replacement, were included in the study. Low serum cortisol (<83 nmol/L) with high plasma adrenocorticotropic hormone (>22 pmol/L) and/or hyperpigmentation of skin/mucous membranes was considered as the diagnostic criteria for Addison's disease. Primary hypothyroidism (both overt and subclinical) was defined as high thyroid stimulating hormone (TSH) with/without low free thyroxine (fT4). TFT and anti-TPO-Ab were performed before and after steroid replacement in all of them. Results: Poststeroid replacement, there was a normalization of TSH in all but one subjects. In overt hypothyroidism patients, fT4 also normalized. The improvement in TFT was not associated with decreasing titer of the anti-TPO-Ab in all six patients. However, there was a significant difference in TSH after steroid replacement compared to the baseline status. Conclusions: The concept of normalization of primary hypothyroidism with cortisol replacement in patients with Addison's disease should be recognized to avoid iatrogenic thyrotoxicosis caused by thyroxine replacement. Both autoimmune and nonautoimmune mechanisms contribute to these alterations. PMID:27042409

Effect of steroid replacement on thyroid function and thyroid autoimmunity in Addison's disease with primary hypothyroidism.

PubMed

Sahoo, Jaya Prakash; Selviambigapathy, Jayakumar; Kamalanathan, Sadishkumar; Nagarajan, K; Vivekanandan, Muthupillai

2016-01-01

Steroid replacement without thyroxine supplementation normalizes thyroid function test (TFT) in some but not all Addison's disease patients with primary hypothyroidism. Both autoimmune and nonautoimmune mechanisms contribute to this improvement in TFT. However, the documentation of the change in thyroid autoimmunity after cortisol replacement is very limited in the literature. The aim of this study was to determine the effect of steroid replacement on TFT and anti-thyroid peroxidase antibody (anti-TPO-Ab) titer in Addison's disease with primary hypothyroidism. This observational study was conducted in a tertiary care center in South India. Six Addison's disease patients with primary hypothyroidism, who were only on steroid replacement, were included in the study. Low serum cortisol (<83 nmol/L) with high plasma adrenocorticotropic hormone (>22 pmol/L) and/or hyperpigmentation of skin/mucous membranes was considered as the diagnostic criteria for Addison's disease. Primary hypothyroidism (both overt and subclinical) was defined as high thyroid stimulating hormone (TSH) with/without low free thyroxine (fT4). TFT and anti-TPO-Ab were performed before and after steroid replacement in all of them. Poststeroid replacement, there was a normalization of TSH in all but one subjects. In overt hypothyroidism patients, fT4 also normalized. The improvement in TFT was not associated with decreasing titer of the anti-TPO-Ab in all six patients. However, there was a significant difference in TSH after steroid replacement compared to the baseline status. The concept of normalization of primary hypothyroidism with cortisol replacement in patients with Addison's disease should be recognized to avoid iatrogenic thyrotoxicosis caused by thyroxine replacement. Both autoimmune and nonautoimmune mechanisms contribute to these alterations.

Contribution of Benson's Relaxation Technique and Brief Psycho-Educational Intervention on Quality of Life of Primary Caregivers of Iranian Children with Chronic Diseases.

PubMed

Mowla, Forough; Khanjari, Sedigheh; Inanlou, Mehrnoush

Chronic diseases leave a significant effect on not only the afflicted children but also their parents. Chronic diseases in children may also influence their parents' or primary caregivers' quality of life (QoL). To determine the effectiveness of a Brief Psycho-educational Intervention (BPI) and Benson's Relaxation Technique (BRT) on the QoL of primary caregivers of children with chronic diseases. The present quasi-experimental pre-test post-test design was conducted on 100 parents with children who had one chronic disease (50 in each of the control and intervention groups) and were admitted to two state-run pediatric hospitals in Tehran, Iran in 2014. The primary caregivers' QoL was assessed using the SF-36 questionnaire before (T1) and four weeks after the intervention (T2). The training was done in four 60-70minute sessions over one week with a 4-week follow-up. Paired t-test, independent t-test, chi-square and Fisher's exact tests were used to analyze the data. On average, large effect sizes (ES≥0.80) were observed after interventions in SF-36 subscales that measured the effect of emotional roles. Small (0.20-0.49) to moderate (0.50-0.79) ESs were found in subscales measuring physical functioning, physical-role, bodily pain, vitality, social functioning and mental health. General health scores remained relatively unchanged at T2. These results suggested that BPI and BRT were effective strategies to improve the QoL of primary caregivers. Furthermore, interventions with low cost, and good safety and outcome could improve the QoL of primary caregivers of children with chronic diseases. Copyright © 2017 Elsevier Inc. All rights reserved.

One size does not fit all: face emotion processing impairments in semantic dementia, behavioural-variant frontotemporal dementia and Alzheimer's disease are mediated by distinct cognitive deficits.

PubMed

Miller, Laurie A; Hsieh, Sharpley; Lah, Suncica; Savage, Sharon; Hodges, John R; Piguet, Olivier

2012-01-01

Patients with frontotemporal dementia (both behavioural variant [bvFTD] and semantic dementia [SD]) as well as those with Alzheimer's disease (AD) show deficits on tests of face emotion processing, yet the mechanisms underlying these deficits have rarely been explored. We compared groups of patients with bvFTD (n = 17), SD (n = 12) or AD (n = 20) to an age- and education-matched group of healthy control subjects (n = 36) on three face emotion processing tasks (Ekman 60, Emotion Matching and Emotion Selection) and found that all three patient groups were similarly impaired. Analyses of covariance employed to partial out the influences of language and perceptual impairments, which frequently co-occur in these patients, provided evidence of different underlying cognitive mechanisms. These analyses revealed that language impairments explained the original poor scores obtained by the SD patients on the Ekman 60 and Emotion Selection tasks, which involve verbal labels. Perceptual deficits contributed to Emotion Matching performance in the bvFTD and AD patients. Importantly, all groups remained impaired on one task or more following these analyses, denoting a primary emotion processing disturbance in these dementia syndromes. These findings highlight the multifactorial nature of emotion processing deficits in patients with dementia.

Complex interactions between potentially pathogenic, opportunistic, and resident bacteria emerge during infection on a reef-building coral.

PubMed

Gignoux-Wolfsohn, Sarah A; Aronson, Felicia M; Vollmer, Steven V

2017-07-01

Increased bacterial diversity on diseased corals can obscure disease etiology and complicate our understanding of pathogenesis. To untangle microbes that may cause white band disease signs from microbes responding to disease, we inoculated healthy Acropora cervicornis corals with an infectious dose from visibly diseased corals. We sampled these dosed corals and healthy controls over time for sequencing of the bacterial 16S region. Endozoicomonas were associated with healthy fragments from 4/10 colonies, dominating microbiomes before dosing and decreasing over time only in corals that displayed disease signs, suggesting a role in disease resistance. We grouped disease-associated bacteria by when they increased in abundance (primary vs secondary) and whether they originated in the dose (colonizers) or the previously healthy corals (responders). We found that all primary responders increased in all dosed corals regardless of final disease state and are therefore unlikely to cause disease signs. In contrast, primary colonizers in the families Pasteurellaceae and Francisellaceae increased solely in dosed corals that ultimately displayed disease signs, and may be infectious foreign bacteria involved in the development of disease signs. Moving away from a static comparison of diseased and healthy bacterial communities, we provide a framework to identify key players in other coral diseases. © FEMS 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Biosecurity procedures for the environmental management of carcasses burial sites in Korea.

PubMed

Kim, Geon-Ha; Pramanik, Sudipta

2016-12-01

Avian influenza and foot-and-mouth disease are two main contagious pathogenic viral disease which are responsible for the massive burials of livestock in Korea since burial is the primary measure to control these outbreaks. Biosecurity is a set of preventive measures designed to prevent the risk of spreading of these infectious diseases. The main objective of this paper is to discuss about the requirements of biosecurity and develop protocol outlines for environmental management of burial sites in Korea. Current practice prescribes to minimize the potential for on-farm pollution and the spread of the infectious diseases. Specific biosecurity procedures such as proper assessment of leachate quality, safe handling and disposal of leachate, adequate leachate pollution monitoring, necessary seasonal management of burial site, and appropriate sterilization process must be carried out to prevent the indirect transmission of pathogens from the burial sites. Policy makers should acquire robust knowledge of biosecurity for establishing more effective future legislation for carcasses disposal in Korea.

Therapy of spondylarthropathy in inflammatory bowel disease.

PubMed

Generini, S; Fiori, G; Matucci Cerinic, M

2002-01-01

Musculoskeletal manifestations represent the most common extra-intestinal complication of inflammatory bowel diseases (IBD) and are usually included in the clinical spectrum of the spondyloarthropathies (SpA). Although control of intestinal inflammation often ameliorates articular symptoms, sometimes arthropathy is independent of the gut disease course and may require the same therapeutic options which apply to primary SpA diseases, but with caution so as not aggravate the IBD. At the moment, salicylates (sulphasalazine and mesalazine) and selective COX-2 inhibitors (which are preferable to traditional NSAIDs although they cannot be assumed to be safe for the gastrointestinal tract) are the first choice treatment. Several immunosuppressive and biological agents including methotrexate, thalidomide and TNFalpha antagonists have efficacy for both articular and intestinal inflammation and are currently in use for the induction of remission and for maintenance in more severe cases. New combination therapies and novel biologically-driven treatments, targeted to specific pathophysiological processes, might offer less toxicity and the potential for better treatment outcomes.

Combined defects in oxidative phosphorylation and fatty acid β-oxidation in mitochondrial disease

PubMed Central

Nsiah-Sefaa, Abena; McKenzie, Matthew

2016-01-01

Mitochondria provide the main source of energy to eukaryotic cells, oxidizing fats and sugars to generate ATP. Mitochondrial fatty acid β-oxidation (FAO) and oxidative phosphorylation (OXPHOS) are two metabolic pathways which are central to this process. Defects in these pathways can result in diseases of the brain, skeletal muscle, heart and liver, affecting approximately 1 in 5000 live births. There are no effective therapies for these disorders, with quality of life severely reduced for most patients. The pathology underlying many aspects of these diseases is not well understood; for example, it is not clear why some patients with primary FAO deficiencies exhibit secondary OXPHOS defects. However, recent findings suggest that physical interactions exist between FAO and OXPHOS proteins, and that these interactions are critical for both FAO and OXPHOS function. Here, we review our current understanding of the interactions between FAO and OXPHOS proteins and how defects in these two metabolic pathways contribute to mitochondrial disease pathogenesis. PMID:26839416

Episodic memory impairment in Addison's disease: results from a telephonic cognitive assessment.

PubMed

Henry, Michelle; Thomas, Kevin G F; Ross, Ian L

2014-06-01

Patients with Addison's disease frequently self-report memory and attention difficulties, even when on standard replacement therapy. However, few published studies examine, using objective measures and assessing across multiple domains, the cognitive functioning of Addison's disease patients relative to healthy controls. The primary aim of this study was to investigate whether the previously reported subjective cognitive deficits in Addison's disease are confirmed by objective measures. Conducting comprehensive neuropsychological assessments of patients with relatively rare clinical disorders, such as Addison's disease, is challenging because access to those patients is often limited, and because their medical condition might prevent extended testing sessions. Brief telephonic cognitive assessments are a useful tool in such circumstances. Hence, we administered the Brief Test of Adult Cognition by Telephone to 27 Addison's disease patients and 27 matched healthy controls. The instrument provides objective assessment of episodic memory, working memory, executive functioning, reasoning, and speed of processing. Statistical analyses confirmed that, as expected, patients performed significantly more poorly than controls on the episodic memory subtest. There were, however, no significant between-group differences on the attention, executive functioning, reasoning, and speed of processing subtests. Furthermore, patients with a longer duration of illness performed more poorly across all domains of cognition. We conclude that, for Addison's disease patients, previously reported subjective cognitive deficits are matched by objective impairment, but only in the domain of episodic memory. Future research might investigate (a) whether these memory deficits are material-specific (i.e., whether non-verbal memory is also affected), and (b) the neurobiological mechanisms underlying these deficits.

Coexistence of Multiple Sclerosis and Brain Tumor: An Uncommon Diagnostic Challenge.

PubMed

Abrishamchi, Fatemeh; Khorvash, Fariborz

2017-01-01

Nonneoplastic demyelinating processes of the brain with mass effect on magnetic resonance imaging can cause diagnostic difficulties. It requires differential diagnosis between the tumefactive demyelinating lesion and the coexistence of neoplasm. We document the case of 41-year-old woman with clinical and radiological findings suggestive of multiple sclerosis. Additional investigations confirmed the coexistence of astrocytoma. This report emphasizes the importance of considering brain tumors in the differential diagnosis of primary demyelinating disease presenting with a cerebral mass lesion.

Collection of family health history for assessment of chronic disease risk in primary care.

PubMed

Powell, Karen P; Christianson, Carol A; Hahn, Susan E; Dave, Gaurav; Evans, Leslie R; Blanton, Susan H; Hauser, Elizabeth; Agbaje, Astrid; Orlando, Lori A; Ginsburg, Geoffrey S; Henrich, Vincent C

2013-01-01

Family health history can predict a patient's risk for common complex diseases. This project assessed the completeness of family health history data in medical charts and evaluated the utility of these data for performing risk assessments in primary care. Family health history data were collected and analyzed to determine the presence of quality indicators that are necessary for effective and accurate assessment of disease risk. More than 99% of the 390 paper charts analyzed contained information about family health history, which was usually scattered throughout the chart. Information on the health of the patient's parents was collected more often than information on the health of other relatives. Key information that was often not collected included age of disease onset, affected side of the family, and second-degree relatives affected. Less than 4% of patient charts included family health histories that were informative enough to accurately assess risk for common complex diseases. Limitations of this study include the small number of charts reviewed per provider, the fact that the sample consisted of primary care providers in a single geographic location, and the inability to assess ethnicity, consanguinity, and other indicators of the informativeness of family health history. The family health histories collected in primary care are usually not complete enough to assess the patient's risk for common complex diseases. This situation could be improved with use of tools that analyze the family health history information collected and provide risk-stratified decision support recommendations for primary care.

Effect of an imaging-based streamlined electronic healthcare process on quality and costs.

PubMed

Bui, Alex A T; Taira, Ricky K; Goldman, Dana; Dionisio, John David N; Aberle, Denise R; El-Saden, Suzie; Sayre, James; Rice, Thomas; Kangarloo, Hooshang

2004-01-01

A streamlined process of care supported by technology and imaging may be effective in managing the overall healthcare process and costs. This study examined the effect of an imaging-based electronic process of care on costs and rates of hospitalization, emergency room (ER) visits, specialist diagnostic referrals, and patient satisfaction. A healthcare process was implemented for an employer group, highlighting improved patient access to primary care plus routine use of imaging and teleconsultation with diagnostic specialists. An electronic infrastructure supported patient access to physicians and communication among healthcare providers. The employer group, a self-insured company, manages a healthcare plan for its employees and their dependents: 4,072 employees were enrolled in the test group, and 7,639 in the control group. Outcome measures for expenses and frequency of hospitalizations, ER visits, traditional specialist referrals, primary care visits, and imaging utilization rates were measured using claims data over 1 year. Homogeneity tests of proportions were performed with a chi-square statistic, mean differences were tested by two-sample t-tests. Patient satisfaction with access to healthcare was gauged using results from an independent firm. Overall per member/per month costs post-implementation were lower in the enrolled population (126 dollars vs 160 dollars), even though occurrence of chronic/expensive diseases was higher in the enrolled group (18.8% vs 12.2%). Lower per member/per month costs were seen for inpatient (33.29 dollars vs 35.59 dollars); specialist referrals (21.36 dollars vs 26.84 dollars); and ER visits (3.68 dollars vs 5.22 dollars). Moreover, the utilization rate for hospital admissions, ER visits, and traditional specialist referrals were significantly lower in the enrolled group, although primary care and imaging utilization were higher. Comparison to similar employer groups showed that the company's costs were lower than national averages (119.24 dollars vs 146.32 dollars), indicating that the observed result was not attributable to normalization effects. Patient satisfaction with access to healthcare ranked in the top 21st percentile. A streamlined healthcare process supported by technology resulted in higher patient satisfaction and cost savings despite improved access to primary care and higher utilization of imaging.

Clinical performance improvement series. Classic CQI integrated with comprehensive disease management as a model for performance improvement.

PubMed

Joshi, M S; Bernard, D B

1999-08-01

In recent years, health and disease management has emerged as an effective means of delivering, integrating, and improving care through a population-based approach. Since 1997 the University of Pennsylvania Health System (UPHS) has utilized the key principles and components of continuous quality improvement (CQI) and disease management to form a model for health care improvement that focuses on designing best practices, using best practices to influence clinical decision making, changing processes and systems to deploy and deliver best practices, and measuring outcomes to improve the process. Experience with 28 programs and more than 14,000 patients indicates significant improvement in outcomes, including high physician satisfaction, increased patient satisfaction, reduced costs, and improved clinical process and outcome measures across multiple diseases. DIABETES DISEASE MANAGEMENT: In three months a UPHS multidisciplinary diabetes disease management team developed a best practice approach for the treatment of all patients with diabetes in the UPHS. After the program was pilot tested in three primary care physician sites, it was then introduced progressively to additional practice sites throughout the health system. The establishment of the role of the diabetes nurse care managers (certified diabetes educators) was central to successful program deployment. Office-based coordinators ensure incorporation of the best practice protocols into routine flow processes. A disease management intranet disseminates programs electronically. Outcomes of the UPHS health and disease management programs so far demonstrate success across multiple dimensions of performance-service, clinical quality, access, and value. The task of health care leadership today is to remove barriers and enable effective implementation of key strategies, such as health and disease management. Substantial effort and resources must be dedicated to gain physician buy-in and achieve compliance. The challenge is to provide leadership support, to reward and recognize best practice performers, and to emphasize the use of data for feedback and improvement. As these processes are implemented successfully, and evidence of improved outcomes is documented, it is likely that this approach will be more widely embraced and that organizationwide performance improvement will increase significantly. Health care has traditionally invested extraordinary resources in developing best practice approaches, including guidelines, education programs, or other tangible products and services. Comparatively little time, effort, and resources have been targeted to implementation and use, the stage at which most efforts fail. CQI's emphasis on data, rapid diffusion of innovative programs, and rapid cycle improvements enhance the implementation and effectiveness of disease management.

Primordial and primary prevention programs for cardiovascular diseases: from risk assessment through risk communication to risk reduction. A review of the literature

PubMed Central

Lancarotte, Inês; Nobre, Moacyr Roberto

2016-01-01

The aim of this study was to identify and reflect on the methods employed by studies focusing on intervention programs for the primordial and primary prevention of cardiovascular diseases. The PubMed, EMBASE, SciVerse Hub-Scopus, and Cochrane Library electronic databases were searched using the terms ‘effectiveness AND primary prevention AND risk factors AND cardiovascular diseases’ for systematic reviews, meta-analyses, randomized clinical trials, and controlled clinical trials in the English language. A descriptive analysis of the employed strategies, theories, frameworks, applied activities, and measurement of the variables was conducted. Nineteen primary studies were analyzed. Heterogeneity was observed in the outcome evaluations, not only in the selected domains but also in the indicators used to measure the variables. There was also a predominance of repeated cross-sectional survey design, differences in community settings, and variability related to the randomization unit when randomization was implemented as part of the sample selection criteria; furthermore, particularities related to measures, limitations, and confounding factors were observed. The employed strategies, including their advantages and limitations, and the employed theories and frameworks are discussed, and risk communication, as the key element of the interventions, is emphasized. A methodological process of selecting and presenting the information to be communicated is recommended, and a systematic theoretical perspective to guide the communication of information is advised. The risk assessment concept, its essential elements, and the relevant role of risk perception are highlighted. It is fundamental for communication that statements targeting other people’s understanding be prepared using systematic data. PMID:27982169

Decreased endothelin receptor B expression in large primary uveal melanomas is associated with early clinical metastasis and short survival

PubMed Central

Smith, S L; Damato, B E; Scholes, A G M; Nunn, J; Field, J K; Heighway, J

2002-01-01

The most devastating aspect of cancer is the metastasis of tumour cells to organs distant from the original tumour site. The major problem facing oncologists treating uveal melanoma, the most common cancer of the eye, is metastatic disease. To lower mortality, it is necessary to increase our understanding of the molecular genetic alterations involved in this process. Using suppression subtractive hybridisation, we have analysed differential gene expression between four primary tumours from patients who have developed clinical metastasis and four primary tumours from patients with no evidence of metastasis to date. We have identified endothelin receptor type B as differentially expressed between these tumours and confirmed this observation using comparative multiplex RT–PCR. In a further 33 tumours, reduced endothelin receptor type B expression correlated with death from metastatic disease. Reduced expression also correlated with other known prognostic indicators, including the presence of epithelioid cells, chromosome 3 allelic imbalance and chromosome 8q allelic imbalance. Endothelin receptor type B expression was also reduced in four out of four primary small cell lung carcinomas compared to normal bronchial epithelium. We also show that the observed down-regulation of endothelin receptor type B in uveal melanoma was not due to gene deletion. Our findings suggest a role for endothelin receptor type B in the metastasis of uveal melanoma and, potentially, in the metastasis of other neural crest tumours. British Journal of Cancer (2002) 87, 1308–1313. doi:10.1038/sj.bjc.6600620 www.bjcancer.com © 2002 Cancer Research UK PMID:12439722

Development of a decision support tool for primary care management of patients with abnormal liver function tests without clinically apparent liver disease: a record-linkage population cohort study and decision analysis (ALFIE).

PubMed

Donnan, P T; McLernon, D; Dillon, J F; Ryder, S; Roderick, P; Sullivan, F; Rosenberg, W

2009-04-01

To determine the natural history of abnormalities in liver function tests (LFTs), derive predictive algorithms for liver disease and identify the most cost-effective strategies for further investigation. MEDLINE database from 1966 to September 2006, EMBASE, CINAHL and the Cochrane Library. Population-based retrospective cohort study set in primary care in Tayside, Scotland, between 1989 and 2003. Participants were patients with no obvious signs of liver disease and registered with a general practitioner (GP). The study followed up those with an incident batch of LFTs in primary care to subsequent liver disease or mortality over a maximum of 15 years. The health technologies being assessed were primary care LFTs, viral and autoantibody tests, ultrasound and liver biopsy. Measures used were the epidemiology of liver disease in Tayside (ELDIT) database, time-to-event modelling, predictive algorithms derived using the Weibull survival model, decision analyses from an NHS perspective, cost-utility analyses, and one-way and two-way sensitivity analyses. A total of 95,977 patients had 364,194 initial LFTs, with a median follow-up of 3.7 years. Of these, 21.7% had at least one abnormal liver function test (ALFT) and 1090 (1.14%) developed liver disease. Elevated transaminases were strongly associated with diagnosed liver disease, with hazard ratios (HRs) of 4.23 [95% CI (confidence interval) 3.55-5.04] for mild levels and 12.67 (95% CI 9.74-16.47) for severe levels versus normal. For gamma-glutamyltransferase (GGT), these HRs were 2.54 (95% CI 2.17-2.96) and 13.44 (10.71-16.87) respectively. Low albumin was strongly associated with all cause mortality, with ratios of 2.65 (95% CI 2.47-2.85) for mild levels and 4.99 (95% CI 4.26-5.84) for severe levels. Sensitivity for predicting events over 5 years was low and specificity was high. Follow-up time was split into baseline to 3 months, 3 months to 1 year and over 1 year. All LFTs were predictive of liver disease, and high probability of liver disease was associated with being female, methadone use, alcohol dependency and deprivation. The shorter-term models had overall c-statistics of 0.85 and 0.72 for outcome of liver disease at 3 months and 1 year respectively, and 0.88 and 0.82 for all cause mortality at 3 months and 1 year respectively. Calibration was good for models predicting liver disease. Discrimination was low for models predicting events at over 1 year. In cost-utility analyses, retesting dominated referral as an option. However, using the predictive algorithms to identify the top percentile at high risk of liver disease, retesting had an incremental cost-utility ratio of 7588 pounds relative to referral. GGT should be included in the batch of LFTs in primary care. If the patient in primary care has no obvious liver disease and a low or moderate risk of liver disease, retesting in primary care is the most cost-effective option. If the patient with ALFTs in primary care has a high risk of liver disease, retesting depends on the willingness to pay of the NHS. Cut-offs are arbitrary and in developing decision aids it is important to treat the LFT results as continuous variables.

Frequency of primary glomerular disease in northeastern China.

PubMed

Wu, Yi-Qi; Wang, Zheng; Xu, Hua-Feng; Jin, Xiao-Ming; Zhou, Hai-Zhou

2011-08-01

Most frequently reported Chinese renal biopsy data have originated from southeastern China. The present study analyzed the renal biopsy data from northeastern China. The records of 1550 consecutive native patients who were diagnosed with primary glomerular diseases (PGD) after renal biopsy at our hospital during 2005-2009 were used. These patients were divided into four age groups for stratified analysis: <15, 15-44, 45-59, and ≥60 years old. Among PGD, minimal change disease (MCD) was the most common histologically diagnosed disease (30.7%), followed by IgA nephropathy (IgAN), mesangial proliferative glomerulonephritis (MsPGN), membranous nephropathy (MN), membranoproliferative glomerulonephritis (MPGN), focal segmental glomerulosclerosis (FSGS), and endocapillary proliferative glomerulonephritis (EnPGN). MCD was the disease most frequently observed (43.7%) in the <15-year-old group. MsPGN was the most common disease in the elderly group (38.1%). MsPGN was more prevalent in females (27.8%), whereas MCD was more prevalent in males (35.3%). Primary glomerular diseases constituted the most commonly encountered group of diseases with a high prevalence of MCD, which predominantly affected males and young adults. The prevalence of MCD was high in northeastern China. Further study is necessary to expand the epidemiologic data available for renal disease in China.

Modelling the effects of booster dose vaccination schedules and recommendations for public health immunization programs: the case of Haemophilus influenzae serotype b.

PubMed

Charania, Nadia A; Moghadas, Seyed M

2017-09-13

Haemophilus influenzae serotype b (Hib) has yet to be eliminated despite the implementation of routine infant immunization programs. There is no consensus regarding the number of primary vaccine doses and an optimal schedule for the booster dose. We sought to evaluate the effect of a booster dose after receiving the primary series on the long-term disease incidence. A stochastic model of Hib transmission dynamics was constructed to compare the long-term impact of a booster vaccination and different booster schedules after receiving the primary series on the incidence of carriage and symptomatic disease. We parameterized the model with available estimates for the efficacy of Hib conjugate vaccine and durations of both vaccine-induced and naturally acquired immunity. We found that administering a booster dose substantially reduced the population burden of Hib disease compared to the scenario of only receiving the primary series. Comparing the schedules, the incidence of carriage for a 2-year delay (on average) in booster vaccination was comparable or lower than that observed for the scenario of booster dose within 1 year after primary series. The temporal reduction of symptomatic disease was similar in the two booster schedules, suggesting no superiority of one schedule over the other in terms of reducing the incidence of symptomatic disease. The findings underscore the importance of a booster vaccination for continued decline of Hib incidence. When the primary series provides a high level of protection temporarily, delaying the booster dose (still within the average duration of protection conferred by the primary series) may be beneficial to maintain longer-term protection levels and decelerate the decline of herd immunity in the population.

Gout and rheumatoid arthritis, both to keep in mind in cardiovascular risk management: A primary care retrospective cohort study.

PubMed

Janssens, Hein J E M; Arts, Paul G J; Schalk, Bianca W M; Biermans, Marion C J

2017-01-01

To assess in one time window cardiovascular risks for both patients with gout and patients with rheumatoid arthritis in a Dutch primary care population. Retrospective matched cohort study with data from the electronic health records of 51 Dutch general practices. Participants were patients aged 30 years or older with an incident diagnosis of gout (n=2655) or rheumatoid arthritis (n=513), and matched non-disease controls (n=7891 and n=1850 respectively). At disease incidence date, patients and controls were compared for prevalence of hypertension, diabetes mellitus, hypercholesterolemia, and prior cardiovascular diseases. Patients without prior cardiovascular disease were followed for a first cardiovascular disease, and compared to controls using Kaplan-Meier survival curves and Cox proportional hazard analyses. Compared to controls, gout patients suffered more from hypertension (44.8%), diabetes (20.1%), hypercholesterolemia (13.7%), and prior cardiovascular disease (30%) (P<0.01), whereas rheumatoid arthritis patients (hypertension 28.5%; diabetes 11.7%; hypercholesterolemia 7.4%; prior cardiovascular disease 11.3%) did not (P>0.05). After adjustment, both gout and rheumatoid arthritis patients without prior cardiovascular disease were more likely to get a cardiovascular disease: hazard ratio (95% confidence interval) 1.44 (1.18 to 1.76), and 2.06 (1.34 to 3.16) respectively. This primary care study indicates that gout and rheumatoid arthritis are both independent risk factors for cardiovascular diseases, rheumatoid arthritis to some greater extent, whereas gout patients at first diagnosis had already an increased cardiovascular risk profile. It gives strong arguments for implementation of both rheumatic diseases in primary care guidelines on cardiovascular risk management. Copyright © 2016 Société française de rhumatologie. Published by Elsevier SAS. All rights reserved.

Effect of an educational intervention on the clinical competence for primary healthcare of rheumatic diseases in Mexican physicians.

PubMed

Cabrera-Pivaral, Carlos E; Ramírez-García, Sergio A; Zavala-González, Marco A

2016-01-01

To measure the effect of an educational intervention on clinical competences for diagnosis and treatment of rheumatic diseases in primary healthcare physicians working in the Guadalajara Metropolitan Area, Jalisco, Mexico. Quasi-experimental study conducted in physicians from two primary health care units. The study was carried out in a 40 physicians sample, 21 in Group "A" (intervention) and 19 in Group "B" (control). The clinical competence for diagnosis and treatment of rheumatic diseases was measured in both groups by means of an instrument previously designed and validated (Kuder-Richardson reliability index =0,94). Clinical competence average score prior to intervention was 47 for Group "A" and 42 for Group "B", while after the intervention it was 72 and 47 respectively, which shows statistically significant differences (Wilcoxon test, p<0,05). Clinical competence for diagnosis and treatment of rheumatic diseases in primary healthcare physicians is low; however, it can be improved by implementing educational interventions based on a constructivist approach.

Is Primary-Process Cognition a Feature of Hypnosis?

PubMed

Finn, Michael T; Goldman, Jared I; Lyon, Gyrid B; Nash, Michael R

2017-01-01

The division of cognition into primary and secondary processes is an important part of contemporary psychoanalytic metapsychology. Whereas primary processes are most characteristic of unconscious thought and loose associations, secondary processes generally govern conscious thought and logical reasoning. It has been theorized that an induction into hypnosis is accompanied by a predomination of primary-process cognition over secondary-process cognition. The authors hypothesized that highly hypnotizable individuals would demonstrate more primary-process cognition as measured by a recently developed cognitive-perceptual task. This hypothesis was not supported. In fact, low hypnotizable participants demonstrated higher levels of primary-process cognition. Exploratory analyses suggested a more specific effect: felt connectedness to the hypnotist seemed to promote secondary-process cognition among low hypnotizable participants.

Lexical decision with pseudohomophones and reading in the semantic variant of primary progressive aphasia: A double dissociation.

PubMed

Boukadi, Mariem; Potvin, Karel; Macoir, Joël; Jr Laforce, Robert; Poulin, Stéphane; Brambati, Simona M; Wilson, Maximiliano A

2016-06-01

The co-occurrence of semantic impairment and surface dyslexia in the semantic variant of primary progressive aphasia (svPPA) has often been taken as supporting evidence for the central role of semantics in visual word processing. According to connectionist models, semantic access is needed to accurately read irregular words. They also postulate that reliance on semantics is necessary to perform the lexical decision task under certain circumstances (for example, when the stimulus list comprises pseudohomophones). In the present study, we report two svPPA cases: M.F. who presented with surface dyslexia but performed accurately on the lexical decision task with pseudohomophones, and R.L. who showed no surface dyslexia but performed below the normal range on the lexical decision task with pseudohomophones. This double dissociation between reading and lexical decision with pseudohomophones is in line with the dual-route cascaded (DRC) model of reading. According to this model, impairments in visual word processing in svPPA are not necessarily associated with the semantic deficits characterizing this disease. Our findings also call into question the central role given to semantics in visual word processing within the connectionist account. Copyright © 2016 Elsevier Ltd. All rights reserved.

From whole body to cellular models of hepatic triglyceride metabolism: man has got to know his limitations

PubMed Central

Green, Charlotte J.; Pramfalk, Camilla; Morten, Karl J.

2014-01-01

The liver is a main metabolic organ in the human body and carries out a vital role in lipid metabolism. Nonalcoholic fatty liver disease (NAFLD) is one of the most common liver diseases, encompassing a spectrum of conditions from simple fatty liver (hepatic steatosis) through to cirrhosis. Although obesity is a known risk factor for hepatic steatosis, it remains unclear what factor(s) is/are responsible for the primary event leading to retention of intrahepatocellular fat. Studying hepatic processes and the etiology and progression of disease in vivo in humans is challenging, not least as NAFLD may take years to develop. We present here a review of experimental models and approaches that have been used to assess liver triglyceride metabolism and discuss their usefulness in helping to understand the aetiology and development of NAFLD. PMID:25352434

Activation of IRF1 in Human Adipocytes Leads to Phenotypes Associated with Metabolic Disease.

PubMed

Friesen, Max; Camahort, Raymond; Lee, Youn-Kyoung; Xia, Fang; Gerszten, Robert E; Rhee, Eugene P; Deo, Rahul C; Cowan, Chad A

2017-05-09

The striking rise of obesity-related metabolic disorders has focused attention on adipocytes as critical mediators of disease phenotypes. To better understand the role played by excess adipose in metabolic dysfunction it is crucial to decipher the transcriptional underpinnings of the low-grade adipose inflammation characteristic of diseases such as type 2 diabetes. Through employing a comparative transcriptomics approach, we identified IRF1 as differentially regulated between primary and in vitro-derived genetically matched adipocytes. This suggests a role as a mediator of adipocyte inflammatory phenotypes, similar to its function in other tissues. Utilizing adipose-derived mesenchymal progenitors we subsequently demonstrated that expression of IRF1 in adipocytes indeed contributes to upregulation of inflammatory processes, both in vitro and in vivo. This highlights IRF1's relevance to obesity-related inflammation and the resultant metabolic dysregulation. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Carbon dioxide-sensing in organisms and its implications for human disease

PubMed Central

Cummins, Eoin P.; Selfridge, Andrew C.; Sporn, Peter H.; Sznajder, Jacob I.; Taylor, Cormac T.

2013-01-01

The capacity of organisms to sense changes in the levels of internal and external gases and to respond accordingly is central to a range of physiologic and pathophysiologic processes. Carbon dioxide, a primary product of oxidative metabolism is one such gas that can be sensed by both prokaryotic and eukaryotic cells and in response to altered levels, elicit the activation of multiple adaptive pathways. The outcomes of activating CO2-sensitive pathways in various species include increased virulence of fungal and bacterial pathogens, prey-seeking behavior in insects as well as taste perception, lung function, and the control of immunity in mammals. In this review, we discuss what is known about the mechanisms underpinning CO2 sensing across a range of species and consider the implications of this for physiology, disease progression, and the possibility of developing new therapeutics for inflammatory and infectious disease. PMID:24045706

Addressing non-communicable diseases in Malaysia: an integrative process of systems and community

PubMed Central

2014-01-01

The prevalence of non-communicable diseases (NCDs) and NCD risk factors in Malaysia have risen substantially in the last two decades. The Malaysian Ministry of Health responded by implementing, “The National Strategic Plan for Non-Communicable Diseases (NSP-NCD) 2010-2014”, and the “NCD Prevention 1Malaysia” (NCDP-1M) programme. This paper outlines the primary health system context in which the NCDP-1M is framed. We also discuss the role of community in facilitating the integration of this programme, and outline some of the key challenges in addressing the sustainability of the plan over the next few years. The paper thus provides an analysis of an integration of a programme that involved a multi-sectoral approach with the view to contributing to a broader discourse on the development of responsive health systems. PMID:25080846

[Evidence based risk assessment of coronary heart disease].

PubMed

Filzmaier, K

2010-06-01

Coronary heart disease (CHD) poses a special challenge for risk assessments. Various kinds of diagnostic or therapeutic procedures, concomitant diseases, risk factors and symptoms need to be connected logically in order to assess the risk of each individual applicant. "Reinsurance manuals" are available to risk assessors in life insurance for this purpose. Using these manuals, the risk assessor can calculate the risk loadings for applicants with specific pre-existing conditions, e.g., CHD. Various tasks thus fall to the reinsurer, which must be able to give grounds for the increased risk loadings, provide the manuals with a process-oriented structure and simultaneously support the primary insurer's business objectives via an intelligent risk assessment. Taking CHD as an example, the following article explains how these tasks can be solved with the aid of medical and mathematical approaches, and how the insurability of applicants with CHD can be extended via the re-evaluation of risks.

Role of the mitochondrial DNA replication machinery in mitochondrial DNA mutagenesis, aging and age-related diseases

PubMed Central

DeBalsi, Karen L.; Hoff, Kirsten E.; Copeland, William C.

2016-01-01

As regulators of bioenergetics in the cell and the primary source of endogenous reactive oxygen species (ROS), dysfunctional mitochondria have been implicated for decades in the process of aging and age-related diseases. Mitochondrial DNA (mtDNA) is replicated and repaired by nuclear-encoded mtDNA polymerase γ (Pol γ) and several other associated proteins, which compose the mtDNA replication machinery. Here, we review evidence that errors caused by this replication machinery and failure to repair these mtDNA errors results in mtDNA mutations. Clonal expansion of mtDNA mutations results in mitochondrial dysfunction, such as decreased electron transport chain (ETC) enzyme activity and impaired cellular respiration. We address the literature that mitochondrial dysfunction, in conjunction with altered mitochondrial dynamics, is a major driving force behind aging and age-related diseases. Additionally, interventions to improve mitochondrial function and attenuate the symptoms of aging are examined. PMID:27143693