Implementing evidence-based patient and family education on oral anticoagulation therapy: a community-based participatory project.

AIMS AND OBJECTIVES: This study aimed at developing and implementing evidence-based patient and family education on oral anticoagulation therapy. BACKGROUND: The number of persons with chronic diseases who live at home is increasing. They have to manage multiple diseases and complex treatments. One such treatment is oral anticoagulation therapy, a high risk variable dose medication. Adherence to oral anticoagulation therapy is jeopardised by limited information about the medications, their risk and complications, the impact of individual daily routine and the limited inclusion of family members in education. Hence, improved and tailored education is essential for patients and families to manage oral anticoagulation therapy at home. DESIGN AND METHODS: A community-based participatory research design combined with the Precede-Proceed model was used including a systematic literature review, posteducation analysis, an online nurse survey, a documentation analysis and patient/family interviews. The study was conducted between April 2010-December 2012 at a department of general internal medicine in a teaching hospital in Switzerland. Participants were the department's nursing and medical professionals including the patients and their families. RESULTS: The evidence-based patient and family education on oral anticoagulation therapy emerged comprising a learning assessment, teaching units, clarification of responsibilities of nurse professionals and documentation guidelines. CONCLUSION AND CLINICAL RELEVANCE: The inclusion of the whole department has contributed to the development and implementation of this evidence-based patient family education on oral anticoagulation therapy, which encompasses local characteristics and patient preferences. This education is now being used throughout the department.

Activating mutations of STAT5B and STAT3 in lymphomas derived from γδ-T or NK cells.

Lymphomas arising from NK or γδ-T cells are very aggressive diseases and little is known regarding their pathogenesis. Here we report frequent activating mutations of STAT3 and STAT5B in NK/T-cell lymphomas (n=51), γδ-T-cell lymphomas (n=43) and their cell lines (n=9) through next generation and/or Sanger sequencing. STAT5B N642H is particularly frequent in all forms of γδ-T-cell lymphomas. STAT3 and STAT5B mutations are associated with increased phosphorylated protein and a growth advantage to transduced cell lines or normal NK cells. Growth-promoting activity of the mutants can be partially inhibited by a JAK1/2 inhibitor. Molecular modelling and surface plasmon resonance measurements of the N642H mutant indicate a marked increase in binding affinity of the phosphotyrosine-Y699 with the mutant histidine. This is associated with the prolonged persistence of the mutant phosphoSTAT5B and marked increase of binding to target sites. Our findings suggest that JAK-STAT pathway inhibition may represent a therapeutic strategy.

Spectrum of digoxin-induced ocular toxicity: a case report and literature review.

BACKGROUND: Digoxin intoxication results in predominantly digestive, cardiac and neurological symptoms. This case is outstanding in that the intoxication occurred in a nonagenarian and induced severe, extensively documented visual symptoms as well as dysphagia and proprioceptive illusions. Moreover, it went undiagnosed for a whole month despite close medical follow-up, illustrating the difficulty in recognizing drug-induced effects in a polymorbid patient. CASE PRESENTATION: Digoxin 0.25 mg qd for atrial fibrillation was prescribed to a 91-year-old woman with an estimated creatinine clearance of 18 ml/min. Over the following 2-3 weeks she developed nausea, vomiting and dysphagia, snowy and blurry vision, photopsia, dyschromatopsia, aggravated pre-existing formed visual hallucinations and proprioceptive illusions. She saw her family doctor twice and visited the eye clinic once until, 1 month after starting digoxin, she was admitted to the emergency room. Intoxication was confirmed by a serum digoxin level of 5.7 ng/ml (reference range 0.8-2 ng/ml). After stopping digoxin, general symptoms resolved in a few days, but visual complaints persisted. Examination by the ophthalmologist revealed decreased visual acuity in both eyes, 4/10 in the right eye (OD) and 5/10 in the left eye (OS), decreased color vision as demonstrated by a score of 1/13 in both eyes (OU) on Ishihara pseudoisochromatic plates, OS cataract, and dry age-related macular degeneration (ARMD). Computerized static perimetry showed non-specific diffuse alterations suggestive of either bilateral retinopathy or optic neuropathy. Full-field electroretinography (ERG) disclosed moderate diffuse rod and cone dysfunction and multifocal ERG revealed central loss of function OU. Visual symptoms progressively improved over the next 2 months, but multifocal ERG did not. The patient was finally discharged home after a 5 week hospital stay. CONCLUSION: This case is a reminder of a complication of digoxin treatment to be considered by any treating physician. If digoxin is prescribed in a vulnerable patient, close monitoring is mandatory. In general, when facing a new health problem in a polymorbid patient, it is crucial to elicit a complete history, with all recent drug changes and detailed complaints, and to include a drug adverse reaction in the differential diagnosis.

Effectiveness of a primary care-based intervention to reduce sitting time in overweight and obese patients (SEDESTACTIV): a randomized controlled trial; rationale and study design

Background: There is growing evidence suggesting that prolonged sitting has negative effects on people's weight, chronic diseases and mortality. Interventions to reduce sedentary time can be an effective strategy to increase daily energy expenditure. The purpose of this study is to evaluate the effectiveness of a six-month primary care intervention to reduce daily of sitting time in overweight and mild obese sedentary patients. Method/Design: The study is a randomized controlled trial (RCT). Professionals from thirteen primary health care centers (PHC) will randomly invite to participate mild obese or overweight patients of both gender, aged between 25 and 65 years old, who spend 6 hours at least daily sitting. A total of 232 subjects will be randomly allocated to an intervention (IG) and control group (CG) (116 individuals each group). In addition, 50 subjects with fibromyalgia will be included. Primary outcome is: (1) sitting time using the activPAL device and the Marshall questionnaire. The following parameters will be also assessed: (2) sitting time in work place (Occupational Sitting and Physical Activity Questionnaire), (3) health-related quality of life (EQ-5D), (4) evolution of stage of change (Prochaska and DiClemente's Stages of Change Model), (5) physical inactivity (catalan version of Brief Physical Activity Assessment Tool), (6) number of steps walked (pedometer and activPAL), (7) control based on analysis (triglycerides, total cholesterol, HDL, LDL, glycemia and, glycated haemoglobin in diabetic patients) and (8) blood pressure and anthropometric variables. All parameters will be assessed pre and post intervention and there will be a follow up three, six and twelve months after the intervention. A descriptive analysis of all variables and a multivariate analysis to assess differences among groups will be undertaken. Multivariate analysis will be carried out to assess time changes of dependent variables. All the analysis will be done under the intention to treat principle. Discussion: If the SEDESTACTIV intervention shows its effectiveness in reducing sitting time, health professionals would have a low-cost intervention tool for sedentary overweight and obese patients management.

Extraintestinal Manifestations of Inflammatory Bowel Disease.

Extraintestinal manifestations (EIM) in inflammatory bowel disease (IBD) are frequent and may occur before or after IBD diagnosis. EIM may impact the quality of life for patients with IBD significantly requiring specific treatment depending on the affected organ(s). They most frequently affect joints, skin, or eyes, but can also less frequently involve other organs such as liver, lungs, or pancreas. Certain EIM, such as peripheral arthritis, oral aphthous ulcers, episcleritis, or erythema nodosum, are frequently associated with active intestinal inflammation and usually improve by treatment of the intestinal activity. Other EIM, such as uveitis or ankylosing spondylitis, usually occur independent of intestinal inflammatory activity. For other not so rare EIM, such as pyoderma gangrenosum and primary sclerosing cholangitis, the association with the activity of the underlying IBD is unclear. Successful therapy of EIM is essential for improving quality of life of patients with IBD. Besides other options, tumor necrosis factor antibody therapy is an important therapy for EIM in patients with IBD.

Non-invasive diagnostic and prognostic evaluation of liver cirrhosis and portal hypertension.

Cirrhosis is the final stage of most of chronic liver diseases, and is almost invariably complicated by portal hypertension, which is the most important cause of morbidity and mortality in these patients. This review will focus on the non-invasive methods currently used in clinical practice for diagnosing liver cirrhosis and portal hypertension. The first-line techniques include physical examination, laboratory parameters, transient elastography and Doppler-US. More sophisticated imaging methods which are less commonly employed are CT scan and MRI, and new technologies which are currently under evaluation are MR elastography and acoustic radiation force imaging (ARFI). Even if none of them can replace the invasive measurement of hepatic venous pressure gradient and the endoscopic screening of gastroesophageal varices, they notably facilitate the clinical management of patients with cirrhosis and portal hypertension, and provide valuable prognostic information.

Incidence and Risk Factors of Abdominal Complications After Lung Transplantation.

BACKGROUND: Due to the underlying diseases and the need for immunosuppression, patients after lung transplantation are particularly at risk for gastrointestinal (GI) complications that may negatively influence long-term outcome. The present study assessed the incidences and impact of GI complications after lung transplantation and aimed to identify risk factors. METHODS: Retrospective analysis of all 227 consecutively performed single- and double-lung transplantations at the University hospitals of Lausanne and Geneva was performed between January 1993 and December 2010. Logistic regressions were used to test the effect of potentially influencing variables on the binary outcomes overall, severe, and surgery-requiring complications, followed by a multiple logistic regression model. RESULTS: Final analysis included 205 patients for the purpose of the present study, and 22 patients were excluded due to re-transplantation, multiorgan transplantation, or incomplete datasets. GI complications were observed in 127 patients (62 %). Gastro-esophageal reflux disease was the most commonly observed complication (22.9 %), followed by inflammatory or infectious colitis (20.5 %) and gastroparesis (10.7 %). Major GI complications (Dindo/Clavien III-V) were observed in 83 (40.5 %) patients and were fatal in 4 patients (2.0 %). Multivariate analysis identified double-lung transplantation (p = 0.012) and early (1993-1998) transplantation period (p = 0.008) as independent risk factors for developing major GI complications. Forty-three (21 %) patients required surgery such as colectomy, cholecystectomy, and fundoplication in 6.8, 6.3, and 3.9 % of the patients, respectively. Multivariate analysis identified Charlson comorbidity index of ≥3 as an independent risk factor for developing GI complications requiring surgery (p = 0.015). CONCLUSION: GI complications after lung transplantation are common. Outcome was rather encouraging in the setting of our transplant center.

Targeted γ-Secretase Inhibition To Control the Notch Pathway in Renal Diseases.

Notch is a membrane inserted protein activated by the membrane-inserted γ-secretase proteolytic complex. The Notch pathway is a potential therapeutic target for the treatment of renal diseases but also controls the function of other cells, requiring cell-targeting of Notch antagonists. Toward selective targeting, we have developed the γ-secretase inhibitor-based prodrugs 13a and 15a as substrates for γ-glutamyltranspeptidase (γ-GT) and/or γ-glutamylcyclotransferase (γ-GCT) as well as aminopeptidase A (APA), which are overexpressed in renal diseases, and have evaluated them in experimental in vitro and in vivo models. In nondiseased mice, the cleavage product from Ac-γ-Glu-γ-secretase inhibitor prodrug 13a (γ-GT-targeting and γ-GCT-targeting) but not from Ac-α-Glu-γ-secretase inhibitor prodrug 15a (APA-targeting) accumulated in kidneys when compared to blood and liver. Potential nephroprotective effects of the γ-secretase inhibitor targeted prodrugs were investigated in vivo in a mouse model of acute kidney injury, demonstrating that the expression of Notch1 and cleaved Notch1 could be selectively down-regulated upon treatment with the Ac-γ-Glu-γ-secretase-inhibitor 13a.

Birth Weight, Working Memory and Epigenetic Signatures in IGF2 and Related Genes: A MZ Twin Study.

Neurodevelopmental disruptions caused by obstetric complications play a role in the etiology of several phenotypes associated with neuropsychiatric diseases and cognitive dysfunctions. Importantly, it has been noticed that epigenetic processes occurring early in life may mediate these associations. Here, DNA methylation signatures at IGF2 (insulin-like growth factor 2) and IGF2BP1-3 (IGF2-binding proteins 1-3) were examined in a sample consisting of 34 adult monozygotic (MZ) twins informative for obstetric complications and cognitive performance. Multivariate linear regression analysis of twin data was implemented to test for associations between methylation levels and both birth weight (BW) and adult working memory (WM) performance. Familial and unique environmental factors underlying these potential relationships were evaluated. A link was detected between DNA methylation levels of two CpG sites in the IGF2BP1 gene and both BW and adult WM performance. The BW-IGF2BP1 methylation association seemed due to non-shared environmental factors influencing BW, whereas the WM-IGF2BP1 methylation relationship seemed mediated by both genes and environment. Our data is in agreement with previous evidence indicating that DNA methylation status may be related to prenatal stress and later neurocognitive phenotypes. While former reports independently detected associations between DNA methylation and either BW or WM, current results suggest that these relationships are not confounded by each other.

Animal modelling for inherited central vision loss.

Disease-causing variants of a large number of genes trigger inherited retinal degeneration leading to photoreceptor loss. Because cones are essential for daylight and central vision such as reading, mobility, and face recognition, this review focuses on a variety of animal models for cone diseases. The pertinence of using these models to reveal genotype/phenotype correlations and to evaluate new therapeutic strategies is discussed. Interestingly, several large animal models recapitulate human diseases and can serve as a strong base from which to study the biology of disease and to assess the scale-up of new therapies. Examples of innovative approaches will be presented such as lentiviral-based transgenesis in pigs and adeno-associated virus (AAV)-gene transfer into the monkey eye to investigate the neural circuitry plasticity of the visual system. The models reported herein permit the exploration of common mechanisms that exist between different species and the identification and highlighting of pathways that may be specific to primates, including humans.

A role of Eye Vergence in Covert Attention

Covert spatial attention produces biases in perceptual and neural responses in the absence of overt orienting movements. The neural mechanism that gives rise to these effects is poorly understood. Here we report the relation between fixational eye movements, namely eye vergence, and covert attention. Visual stimuli modulate the angle of eye vergence as a function of their ability to capture attention. This illustrates the relation between eye vergence and bottom-up attention. In visual and auditory cue/no-cue paradigms, the angle of vergence is greater in the cue condition than in the no-cue condition. This shows a top-down attention component. In conclusion, observations reveal a close link between covert attention and modulation in eye vergence during eye fixation. Our study suggests a basis for the use of eye vergence as a tool for measuring attention and may provide new insights into attention and perceptual disorders.

Evaluation of preoperative computed tomography angiography in association with conventional angiography versus computed tomography angiography only, in the endovascular treatment of aortic diseases

Objective To evaluate the association of conventional angiography (AG) with computed tomography angiography (CTA) as compared with CTA only, preoperatively, in the treatment of aortic diseases. Materials and Methods Retrospective study involving patients submitted to endovascular treatment of aortic diseases, in the period from January 2009 to July 2010, with use of preoperative CTA + conventional AG or CTA only. The patients were divided into two groups, namely: G1 – thoracic aortic diseases; and G2 – abdominal aortic diseases. G1 was subdivided into 1A (preoperative AG + CTA) and 1B (preoperative CTA). G2 was subdivided into 2C (CTA + AG) and 2D (CTA only). Results The authors evaluated 156 patients. In subgroups 1A and 1B, the rate of technical success was, respectively, 100% and 94.7% (p = 1.0); and the rate of therapeutic success was, respectively, 81% and 58% (p = 0.13). A higher number of complications were observed in subgroup 1B (p = 0.057). The accuracy in the calculation of the prosthesis was higher in subgroup 1A (p = 0.065). In their turn, the rate of technical success in subgroups 2C and 2D was, respectively, 92.3% and 98.6% (p = 0.17). The rate of therapeutic success was 73% and 98.6% (p = 0.79). Conclusion Preoperative conventional AG should be reserved for cases where CTA cannot provide all the information in the planning of a therapeutic intervention.

Health Migration Policies and Ethical Controversies: the Case of African Nurses in the UK

The United Kingdom (UK) for last few decades has been faced with a growing need for health personnel and has therefore attracted professionals, particularly overseas nurses. The country has been characterised by a historical migration policy favourable to the recruitment of foreign health staff. However, in the context of deep shortage and high level of diseases and health system weakness, the international health professional recruitment from Sub Saharan Africa has created unprecedented ethical controversies which have pushed the UK to the centre of discussions because of its liberal policies towards international recruitment that have been considered as aggressive. While the 'brain drain' controversy is well known, less attention has been devoted to the specific international health migration controversy and the pivotal role of the UK in the diffusion of ethical code of practice. Using mainly the perspective of the policy analysis of controversy (Roe 1994) and the analysis of discourses (de Haas 2008), our paper comes back respectively to the nature of the controversy and the pivotal role of the UK. It also analyses how the implementation of UK ethical policies - Code of Practice, banned countries list of recruitment, restrictive immigration policies - have been considered as inefficient and unethical in their contents and their targets.

A feasability study of the analysis of the economic outcomes of specialized nutrition in obesity and weight management in Switzerland

The increasing prevalence of obesity and its associated complications requires specialized care to improve outcomes and control health care costs. Obesity is associated with numerous serious and costly medical problems requiring specialized care in managing health. The economic burden of obesity includes increased inpatient and outpatient medical expenditures as well as employer-related issues of absenteeism and associate costs. The objectives of this study are: - To describe the health consequences and the economic burden of obesity, - To review the existing treatment - To argue in favor of a specialized nutritional intervention that has shown to improve health and reduce obesity related health care costs. Therefore, expose the possibility of introducing the specialized nutrition in Switzerland and the feasibility of this project considering the medical trends and reimbursement system in Switzerland The benefits and outcomes for the patients will be the significant weight loss which reduces the severity and risk factors for complications and the improved health and quality of life. Weight loss will be a combination of a diet, exercise and behavioral interventions which are the basic recommendations for obesity treatment in addition to the specialized nutritional support. By nutritional support, we mean products that are intended to provide nutritional support in the dietary management of people with specific diseases and conditions when adequate intake of regular foods is compromised. These products are called, Food for special medical purposes FSMP. They are not intended to treat, cure, prevent, mitigate or have a direct impact on disease in a manner similar to drugs or other medical treatments and should be used under medical supervision. They also provide a low cost alternative to surgery. From a health care system perspective, the specialized nutrition will drive its advantage by reducing the utilization of medical services for obesity associated complications like medication, physician's consultations and surgical interventions arriving to a cost effective care for the hospitals, the health care organizations and the third party payers which are the health insurances. [Author, p. 4]

Mechanisms of protein homeostasis in health, aging and disease.

When emerging from the ribosomes, new polypeptides need to fold properly, eventually translocate, and then assemble into stable, yet functionally flexible complexes. During their lifetime, native proteins are often exposed to stresses that can partially unfold and convert them into stably misfolded and aggregated species, which can in turn cause cellular damage and propagate to other cells. In animal cells, especially in aged neurons, toxic aggregates may accumulate, induce cell death and lead to tissue degeneration via different mechanisms, such as apoptosis as in Parkinson's and Alzheimer's diseases and aging in general. The main cellular mechanisms effectively controlling protein homeostasis in youth and healthy adulthood are: (1) the molecular chaperones, acting as aggregate unfolding and refolding enzymes, (2) the chaperone-gated proteases, acting as aggregate unfolding and degrading enzymes, (3) the aggresomes, acting as aggregate compacting machineries, and (4) the autophagosomes, acting as aggregate degrading organelles. For unclear reasons, these cellular defences become gradually incapacitated with age, leading to the onset of degenerative diseases. Understanding these mechanisms and the reasons for their incapacitation in late adulthood is key to the design of new therapies against the progression of aging, degenerative diseases and cancers.