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1.
Respir Med ; 216: 107294, 2023 09.
Article in English | MEDLINE | ID: mdl-37295536

ABSTRACT

The term GETomics has been recently proposed to illustrate that human health and disease are actually the final outcome of many dynamic, interacting and cumulative gene (G) - environment (E) interactions that occur through the lifetime (T) of the individual. According to this new paradigm, the final outcome of any GxE interactions depends on both the age of the individual at which such GxE interaction occurs as well as on the previous, cumulative history of previous GxE interactions through the induction of epigenetic changes and immune memory (both lasting overtime). Following this conceptual approach, our understanding of the pathogenesis of chronic obstructive pulmonary disease (COPD) has changed dramatically. Traditionally believed to be a self-inflicted disease induced by tobacco smoking occurring in older men and characterized by an accelerated decline of lung function with age, now we understand that there are many other risk factors associated with COPD, that it occurs also in females and young individuals, that there are different lung function trajectories through life, and that COPD is not always characterized by accelerated lung function decline. In this paper we discuss how a GETomics approach to COPD may open new perspectives to better understand its relationship with exercise limitation and the ageing process.


Subject(s)
Pulmonary Disease, Chronic Obstructive , Male , Female , Humans , Aged , Pulmonary Disease, Chronic Obstructive/complications , Aging/genetics , Risk Factors , Lung , Spirometry/adverse effects
2.
Rev. neurol. (Ed. impr.) ; 76(1): 21-30, Ene. 2023. tab
Article in Spanish | IBECS | ID: ibc-214338

ABSTRACT

Introducción: La esclerosis múltiple afecta principalmente a mujeres en edad fértil, y el período de gestación y posparto es de especial interés por las peculiaridades que comporta en cuanto a evolución de la enfermedad y por las consecuencias terapéuticas que se derivan. En el período de lactancia materna (LM), la elección de la estrategia de tratamiento debe poner en una balanza, por un lado, los beneficios bien establecidos de la LM para el recién nacido y su madre y, por el otro, el perfil de seguridad y potenciales efectos adversos en el lactante derivados de la exposición a los fármacos modificadores de la enfermedad, por transferencia a través de leche materna. Desarrollo: Se realiza una revisión de la evidencia actual acerca de la seguridad de los fármacos modificadores de la enfermedad disponibles para el tratamiento de la esclerosis múltiple durante el período de LM, y se recogen datos de transferencia de los diferentes fármacos a la leche materna, así como los potenciales efectos adversos descritos en el lactante. Los fármacos considerados de primera elección durante este período son el interferón beta y el acetato de glatiramer. El resto de los fármacos modificadores de la enfermedad no están aceptados para su utilización en el período de LM por ficha técnica. Sin embargo, en los últimos años, se han publicado datos de estudios de práctica clínica y series de casos que indican que algunos de estos fármacos podrían utilizarse con seguridad durante este período. Conclusiones: Teniendo en cuenta los beneficios reconocidos de la LM para la salud tanto de la madre como del lactante, se debe recomendar la LM exclusiva a las pacientes con esclerosis múltiple siempre que sea posible. Es fundamental realizar una evaluación individualizada previa al embarazo y valorar las diferentes opciones de tratamiento en función de cada paciente.(AU)


Introduction: Multiple sclerosis mainly affects women of childbearing age, and the pregnancy and postpartum period is of special interest because of the peculiarities of the disease course and the therapeutic consequences that derive from it. During the period of breastfeeding (BF), the choice of treatment strategy must weigh up the well-established benefits of BF for both the newborn and the mother against the safety profile and potential adverse effects on the infant resulting from exposure to disease-modifying drugs transferred through breast milk. Development: The study reviews the current evidence on the safety of disease-modifying drugs available for the treatment of multiple sclerosis during the BF period, and gathers data on the transfer of the different drugs into breast milk, as well as the potential adverse effects described in the infant. The drugs of first choice during this period are interferon beta and glatiramer acetate. The rest of the disease modifying drugs are not accepted for use in the BF period according to their summary of product characteristics. However, in recent years, data from studies of clinical practice and case series have been published suggesting that some of these drugs could be used safely during this period. Conclusions: Given the recognised health benefits of BF for both mother and infant, exclusive breastfeeding is recommended whenever possible. It is essential to carry out an individualised assessment prior to pregnancy and to evaluate the different treatment options depending on each patient.(AU)


Subject(s)
Humans , Male , Female , Breast Feeding , Multiple Sclerosis , Postpartum Period , Family Development Planning , Antirheumatic Agents , Rheumatic Diseases
3.
Rev Neurol ; 76(1): 21-30, 2023 01 01.
Article in Spanish | MEDLINE | ID: mdl-36544373

ABSTRACT

INTRODUCTION: Multiple sclerosis mainly affects women of childbearing age, and the pregnancy and postpartum period is of special interest because of the peculiarities of the disease course and the therapeutic consequences that derive from it. During the period of breastfeeding (BF), the choice of treatment strategy must weigh up the well-established benefits of BF for both the newborn and the mother against the safety profile and potential adverse effects on the infant resulting from exposure to disease-modifying drugs transferred through breast milk. DEVELOPMENT: The study reviews the current evidence on the safety of disease-modifying drugs available for the treatment of multiple sclerosis during the BF period, and gathers data on the transfer of the different drugs into breast milk, as well as the potential adverse effects described in the infant. The drugs of first choice during this period are interferon beta and glatiramer acetate. The rest of the disease modifying drugs are not accepted for use in the BF period according to their summary of product characteristics. However, in recent years, data from studies of clinical practice and case series have been published suggesting that some of these drugs could be used safely during this period. CONCLUSIONS: Given the recognised health benefits of BF for both mother and infant, exclusive breastfeeding is recommended whenever possible. It is essential to carry out an individualised assessment prior to pregnancy and to evaluate the different treatment options depending on each patient.


TITLE: Fármacos modificadores de la enfermedad en la esclerosis múltiple durante la lactancia: revisión de la evidencia actual.Introducción. La esclerosis múltiple afecta principalmente a mujeres en edad fértil, y el período de gestación y posparto es de especial interés por las peculiaridades que comporta en cuanto a evolución de la enfermedad y por las consecuencias terapéuticas que se derivan. En el período de lactancia materna (LM), la elección de la estrategia de tratamiento debe poner en una balanza, por un lado, los beneficios bien establecidos de la LM para el recién nacido y su madre y, por el otro, el perfil de seguridad y potenciales efectos adversos en el lactante derivados de la exposición a los fármacos modificadores de la enfermedad, por transferencia a través de leche materna. Desarrollo. Se realiza una revisión de la evidencia actual acerca de la seguridad de los fármacos modificadores de la enfermedad disponibles para el tratamiento de la esclerosis múltiple durante el período de LM, y se recogen datos de transferencia de los diferentes fármacos a la leche materna, así como los potenciales efectos adversos descritos en el lactante. Los fármacos considerados de primera elección durante este período son el interferón beta y el acetato de glatiramer. El resto de los fármacos modificadores de la enfermedad no están aceptados para su utilización en el período de LM por ficha técnica. Sin embargo, en los últimos años, se han publicado datos de estudios de práctica clínica y series de casos que indican que algunos de estos fármacos podrían utilizarse con seguridad durante este período. Conclusiones. Teniendo en cuenta los beneficios reconocidos de la LM para la salud tanto de la madre como del lactante, se debe recomendar la LM exclusiva a las pacientes con esclerosis múltiple siempre que sea posible. Es fundamental realizar una evaluación individualizada previa al embarazo y valorar las diferentes opciones de tratamiento en función de cada paciente.


Subject(s)
Breast Feeding , Multiple Sclerosis , Infant , Infant, Newborn , Pregnancy , Humans , Female , Multiple Sclerosis/drug therapy , Glatiramer Acetate/therapeutic use , Interferon-beta/therapeutic use
4.
Respir Med ; 192: 106726, 2022 02.
Article in English | MEDLINE | ID: mdl-35032737

ABSTRACT

RATIONALE: Recent guidelines consider chronic cough to be a unique clinical entity with different phenotypes. We aimed to investigate them in a general population and to describe prevalence, distribution, and characteristics of these phenotypes within the Austrian general population. METHODS: From the LEAD study, a longitudinal observational population-based cohort, data from questionnaires and spirometry of 10,057 adult participants was analysed. Chronic cough was defined as coughing nearly every day during the last 12 months for at least 3 months (>12 weeks). RESULTS: The prevalence of chronic cough was 9% and increased with age. We found no sex predominance but a female preponderance (68%) in never smokers. A presumable cause was identified in 85% of which more than half (53.9%) had two phenotypes, 36.9% belonged to one only and 9.2% to three or more. Regarding the distribution of phenotypes, 40.8% were current smokers, 32.6% had an ACE inhibitor intake, 18.2% GERD, 17.6% asthmatic cough, 9.7% UACS and 28.3% other diseases associated with chronic cough. 15% had unexplained chronic cough with no identifiable phenotype. Current smoking, low socioeconomic status, obesity, COPD and obstructive sleep apnea were associated factors with chronic cough. CONCLUSION: Chronic cough is common among adults in Austria and highly prevalent in the older population. Most participants can be phenotyped with simple questionnaire-based assessment and can therefore potentially receive specific treatment without intensive clinical workup.


Subject(s)
Cough , Pulmonary Disease, Chronic Obstructive , Austria/epidemiology , Cough/epidemiology , Cough/etiology , Cross-Sectional Studies , Female , Humans , Phenotype , Prevalence , Spirometry
5.
Phys Rev Lett ; 125(2): 020502, 2020 Jul 10.
Article in English | MEDLINE | ID: mdl-32701323

ABSTRACT

We show that the states generated by a three-mode spontaneous parametric down-conversion (SPDC) interaction Hamiltonian possess tripartite entanglement of a different nature to other paradigmatic three-mode entangled states generated by the combination of two-mode SPDC interactions. While two-mode SPDC generates Gaussian states whose entanglement can be characterized by standard criteria based on two-mode quantum correlations, these criteria fail to capture the entanglement generated by three-mode SPDC. We use criteria built from three-mode correlation functions to show that the class of states recently generated in a superconducting-circuit implementation of three-mode SPDC ideally have tripartite entanglement, contrary to recent claims in the literature. These criteria are suitable for triple SPDC but we show that they fail to detect tripartite entanglement in other states which are known to possess it, which illustrates the existence of two fundamentally different notions of tripartite entanglement in three-mode continuous-variable systems.

6.
Crit Rev Toxicol ; 49(7): 580-596, 2019 08.
Article in English | MEDLINE | ID: mdl-31846383

ABSTRACT

An environmental risk assessment (ERA) consists of an analysis of the risks to human health and the environment that a medicinal product may cause due to its release during clinical development or after entering the market. Regulators in European Union (EU) and the United States (US) require that advanced therapy medicinal products (ATMPs) that are also genetically modified organisms (GMOs) undergo an ERA in order to be approved for marketing authorization. This work aims to review the regulatory issues that need to be taken into consideration for carrying out an ERA, comparing the EU and the US. The European regulatory framework for environmental procedures and the dissimilarities in its implementation across the Member States and its implications at a logistical level are analyzed in detail. In addition, this review provides a brief insight into the non-clinical and clinical assessments that should be carried out during the development of the product in order to conduct a successful ERA, and thus facilitate its marketing authorization and post-marketing monitoring. Finally, the need for a European harmonization regarding environmental procedures for ATMPs is discussed.


Subject(s)
Environmental Pollutants , Pharmaceutical Preparations , Environmental Monitoring , Environmental Policy , European Union , Humans , Marketing , Risk Assessment , United States
7.
Int J Tuberc Lung Dis ; 23(11): 1131-1141, 2019 11 01.
Article in English | MEDLINE | ID: mdl-31718748

ABSTRACT

Chronic obstructive pulmonary disease (COPD) is one of the top three causes of death worldwide, but governments and non-governmental organisations have not given its prevention and treatment the priority it requires. This is particularly true in low- and middle-income countries, where most of the people suffering from this disease live. The United Nations (UN) has targeted a reduction of premature deaths from non-communicable diseases (NCDs) by a third by 2030; however, a coordinated UN/World Health Organization (WHO) strategy to address the burden of COPD (one of the most important NCDs) is still lacking. To explore the extent of the problem and inform the development of policies to improve the situation, the Board of Directors of the Global Initiative for Chronic Obstructive Lung Disease (GOLD) held a 1-day Summit. The key themes that emerged were the need to ensure accurate data on prevalence, raise awareness of the disease among the public, healthcare professionals and governments, including the fact that COPD aetiology goes beyond smoking (and other inhaled pollutants) and includes poor lung development in early life, and ensure that spirometry and both pharmacological and non-pharmacological therapies are available and affordable. Here, we present the actions that must be taken to address the impact of COPD. We believe that the WHO is particularly well-positioned to co-ordinate an attack on COPD, and GOLD will do all it can to help and rally support.


Subject(s)
Developing Countries , Pulmonary Disease, Chronic Obstructive/diagnosis , Pulmonary Disease, Chronic Obstructive/epidemiology , Pulmonary Disease, Chronic Obstructive/prevention & control , Delivery of Health Care/standards , Diagnostic Techniques, Respiratory System/standards , Global Health , Humans , Practice Guidelines as Topic , Prevalence , Risk Factors , World Health Organization
9.
Lung Cancer ; 135: 230-233, 2019 09.
Article in English | MEDLINE | ID: mdl-31235316

ABSTRACT

OBJECTIVES: To investigate the capacity of a trained dog to identify LC in patients with malignant SPN. METHODS: We collected 90 exhaled gas samples from 30 patients with SPN (3 samples/patient). As controls we used 61 healthy volunteers and 18 COPD patients without SNP or LC, in each of whom we collected 5 exhaled gas samples (n = 395). The dog (Blat, a 4-year-old crossbreed between a Labrador Retriever and a Pitbull) and the methodology used were the same as previously reported by our group (see: https://drive.google.com/open?id=1R4mOtOtuZkTeb5iOEEv0K9r2kHKlPhWd). RESULTS: Of 30 patients with SPN, Blat recognized 27 of them as positive for LC and 3 as negative for LC. These results fully matched post-surgical pathological results. Sensibility was 0.97, Specificity 0.99, Positive Predictive value 0.97 and negative predictive value 0.99. The AUC of the ROC curve was 0.985. CONCLUSIONS: Trained dogs can identify accurately the malignant origin of SPN. It is now time to develop technology that can match canine olfaction and facilitate the implementation of this diagnostic approach in the clinic.


Subject(s)
Lung Neoplasms/diagnosis , Solitary Pulmonary Nodule/diagnosis , Aged , Animals , Case-Control Studies , Diagnosis, Differential , Disease Models, Animal , Dogs , Female , Humans , Lung Neoplasms/pathology , Male , Middle Aged , Neoplasm Grading/methods , ROC Curve , Reproducibility of Results , Solitary Pulmonary Nodule/pathology
10.
J Investig Allergol Clin Immunol ; 29(3): 168-179, 2019.
Article in English | MEDLINE | ID: mdl-30561365

ABSTRACT

There is growing evidence that events occurring early in life, both before and after birth, are significantly associated with the risk of asthma, chronic obstructive pulmonary disease, and diminished lung function later in life. In fact, from conception to death, a series of continuous, dynamic gene-environment interactions determine 2 fundamental biological processes, namely, lung development and lung aging. Over 130 birth cohorts have been initiated in the last 30 years. Data from these cohorts have improved our understanding of the inception, progression, and persistency of asthma. In this review, we summarize the main data for the early life events proven to determine later development and persistence of asthma, such as maternal atopy and smoking, preterm birth/bronchopulmonary dysplasia, infections, nutrition, obesity, smoking, and other environmental exposures in childhood and adolescence. While some of these factors are obviously impossible to prevent or eliminate, others have been proven to have a protective role, and current research is aimed optimizing them. Available prophylactic measures are also reviewed. In the case of environmental pollution, large scale political interventions successfully managed to decrease contamination levels, leading to improved lung function and lower asthma prevalence in the respective geographical areas. Future research should focus on better understanding these complex interactions in order to develop and enhance effective preventive therapeutic measures.


Subject(s)
Hypersensitivity, Immediate/immunology , Lung/physiology , Prenatal Exposure Delayed Effects/immunology , Pulmonary Disease, Chronic Obstructive/immunology , Animals , Asthma , Child , Female , Gene-Environment Interaction , Genetic Predisposition to Disease , Humans , Hypersensitivity, Immediate/epidemiology , Hypersensitivity, Immediate/genetics , Infant, Newborn , Pregnancy , Prenatal Exposure Delayed Effects/epidemiology , Prenatal Exposure Delayed Effects/genetics , Pulmonary Disease, Chronic Obstructive/epidemiology , Risk Factors , Spain/epidemiology
11.
J. investig. allergol. clin. immunol ; 29(3): 168-179, 2019. tab, graf
Article in English | IBECS | ID: ibc-184084

ABSTRACT

There is growing evidence that events occurring early in life, both before and after birth, are significantly associated with the risk of asthma, chronic obstructive pulmonary disease, and diminished lung function later in life. In fact, from conception to death, a series of continuous, dynamic gene-environment interactions determine 2 fundamental biological processes, namely, lung development and lung aging. Over 130 birth cohorts have been initiated in the last 30 years. Data from these cohorts have improved our understanding of the inception, progression, and persistency of asthma. In this review, we summarize the main data for the early life events proven to determine later development and persistence of asthma, such as maternal atopy and smoking, preterm birth/bronchopulmonary dysplasia, infections, nutrition, obesity, smoking, and other environmental exposures in childhood and adolescence. While some of these factors are obviously impossible to prevent or eliminate, others have been proven to have a protective role, and current research is aimed optimizing them. Available prophylactic measures are also reviewed. In the case of environmental pollution, large scale political interventions successfully managed to decrease contamination levels, leading to improved lung function and lower asthma prevalence in the respective geographical areas. Future research should focus on better understanding these complex interactions in order to develop and enhance effective preventive therapeutic measures


Existe evidencia de que eventos que ocurren en fases tempranas de la vida, tanto antes como después del nacimiento, se asocian significativamente con el aumento del riesgo futuro de asma, enfermedad pulmonar obstructiva crónica y deterioro de la función pulmonar. En efecto, desde el momento de la concepción hasta la muerte, una serie de interacciones dinámicas y continuas genético-ambientales determinan dos procesos biológicos fundamentales, el desarrollo pulmonar y el envejecimiento pulmonar. En los últimos 30 años se han comenzado más de 130 cohortes de nacimiento. Los datos de estas cohortes han mejorado nuestra comprensión del inicio, la progresión y la persistencia del asma. En esta revisión, resumimos los datos principales de los eventos de la vida temprana probados que determinan el desarrollo y la persistencia posteriores del asma, como atopia materna y tabaquismo, parto prematuro/displasia broncopulmonar, infecciones, nutrición, obesidad, tabaquismo y otras exposiciones ambientales en la infancia y la adolescencia. Si bien algunos de estos factores son obviamente imposibles de prevenir o eliminar, se ha demostrado que otros tienen un papel protector, y la investigación actual apunta a optimizarlos. También se revisan las medidas profilácticas disponibles. En el caso de la contaminación ambiental, las intervenciones políticas a gran escala lograron disminuir los niveles de contaminación, lo que mejoró la función pulmonar y disminuyó la prevalencia de asma en las respectivas áreas geográficas. Las investigaciones futuras deberían centrarse en comprender mejor estas interacciones complejas para desarrollar y mejorar las medidas terapéuticas preventivas eficaces


Subject(s)
Humans , Asthma/etiology , Hypersensitivity, Immediate/immunology , Asthma/immunology , Respiratory Function Tests/statistics & numerical data , Evaluation of Results of Preventive Actions/trends , Pulmonary Disease, Chronic Obstructive/prevention & control , Bronchial Hyperreactivity/prevention & control , Pregnancy Complications
12.
Br J Surg ; 105(12): 1583-1590, 2018 11.
Article in English | MEDLINE | ID: mdl-30238438

ABSTRACT

BACKGROUND: The majority of lesions resulting in pathological nipple discharge are benign. Conventional surgery is undirected and targeting the causative lesion by duct endoscopy may enable more accurate surgery with fewer complications. METHODS: Patients requiring microdochectomy and/or major duct excision were randomized to duct endoscopy or no duct endoscopy before surgery. Primary endpoints were successful visualization of the pathological lesion in patients randomized to duct endoscopy, and a comparison of the causative pathology between the two groups. The secondary endpoint was to compare the specimen size between groups. RESULTS: A total of 68 breasts were studied in 66 patients; there were 31 breasts in the duct endoscopy group and 37 in the no-endoscopy group. Median age was 49 (range 19-81) years. Follow-up was 5·4 (i.q.r. 3·3-8·9) years in the duct endoscopy group and 5·7 (3·1-9·0) years in no-endoscopy group. Duct endoscopy had a sensitivity of 80 (95 per cent c.i. 52 to 96) per cent, specificity of 71 (44 to 90) per cent, positive predictive value of 71 (44 to 90) per cent and negative predictive value of 80 (52 to 96) per cent in identifying any lesion. There was no difference in causative pathology between the groups. Median volume of the surgical resection specimen did not differ between groups. CONCLUSION: Diagnostic duct endoscopy is useful for identifying causative lesions of nipple discharge. Duct endoscopy did not influence the pathological yield of benign or malignant diagnoses nor surgical resection volumes. Registered as INTEND II in CancerHelp UK clinical trials database (https://www.cancerresearchuk.org/about-cancer/find-a-clinical-trial/a-study-looking-at-changes-inside-the-breast-ducts-of-women-who-have-nipple-discharge).


Subject(s)
Breast Diseases/surgery , Endoscopy/methods , Nipple Discharge , Nipples/surgery , Adult , Aged , Aged, 80 and over , Ambulatory Surgical Procedures/statistics & numerical data , Breast Diseases/pathology , Breast Neoplasms/pathology , Female , Humans , Intraoperative Care/methods , Middle Aged , Papilloma, Intraductal/pathology , Preoperative Care/methods , Treatment Outcome , Young Adult
13.
Br J Hosp Med (Lond) ; 79(1): 8-11, 2018 Jan 02.
Article in English | MEDLINE | ID: mdl-29315044
14.
Neurotox Res ; 33(2): 247-258, 2018 02.
Article in English | MEDLINE | ID: mdl-28975519

ABSTRACT

It has been proposed that developmental exposure to pesticides contributes to increasing prevalence of neurodevelopmental disorders in children, such as attention deficit with hyperactivity (ADHD) and to alterations in coordination skills. However, the mechanisms involved in these alterations remain unclear. We analyzed the effects on spontaneous motor activity and motor coordination of developmental exposure to a representative pesticide of each one of the four main chemical families: organophosphates (chlorpyrifos), carbamates (carbaryl), organochlorines (endosulfan), and pyrethroids (cypermethrin). Pesticides were administered once a day orally, in a sweet jelly, from gestational day 7 to post natal day 21. Spontaneous motor activity was assessed by an actimeter and motor coordination using the rotarod, when rats were adults. The effects were analyzed separately in males and females. Extracellular GABA in cerebellum and NMDA receptor subunits in hippocampus were assessed as possible underlying mechanisms of motor alterations. Motor coordination was impaired by developmental exposure to endosulfan, cypermethrin, and chlorpyrifos in females but not in males. The effect of endosulfan and cypermethrin would be due to increased extracellular GABA in cerebellum, which remains unaltered in male rats. Chlorpyrifos increased motor activity in males and females. Cypermethrin decreased motor activity mainly in males. In male rats, but not in females, expression of the NR2B subunit of NMDA receptor in hippocampus correlated with motor activity. These results show sex-specific effects of different pesticides on motor activity and coordination, associated with neurotransmission alterations. These data contribute to better understand the relationship between developmental exposure to the main pesticide families and motor disorders in children.


Subject(s)
Behavior, Animal/drug effects , Motor Activity/drug effects , Pesticides/pharmacology , Prenatal Exposure Delayed Effects/metabolism , Sex Characteristics , Animals , Attention Deficit Disorder with Hyperactivity/drug therapy , Attention Deficit Disorder with Hyperactivity/physiopathology , Female , Hippocampus/drug effects , Hippocampus/metabolism , Male , Pregnancy , Prenatal Exposure Delayed Effects/drug therapy , Rats, Wistar , Receptors, N-Methyl-D-Aspartate/metabolism
16.
Clin Transl Allergy ; 6: 29, 2016.
Article in English | MEDLINE | ID: mdl-27478588

ABSTRACT

Action Plan B3 of the European Innovation Partnership on Active and Healthy Ageing (EIP on AHA) focuses on the integrated care of chronic diseases. Area 5 (Care Pathways) was initiated using chronic respiratory diseases as a model. The chronic respiratory disease action plan includes (1) AIRWAYS integrated care pathways (ICPs), (2) the joint initiative between the Reference site MACVIA-LR (Contre les MAladies Chroniques pour un VIeillissement Actif) and ARIA (Allergic Rhinitis and its Impact on Asthma), (3) Commitments for Action to the European Innovation Partnership on Active and Healthy Ageing and the AIRWAYS ICPs network. It is deployed in collaboration with the World Health Organization Global Alliance against Chronic Respiratory Diseases (GARD). The European Innovation Partnership on Active and Healthy Ageing has proposed a 5-step framework for developing an individual scaling up strategy: (1) what to scale up: (1-a) databases of good practices, (1-b) assessment of viability of the scaling up of good practices, (1-c) classification of good practices for local replication and (2) how to scale up: (2-a) facilitating partnerships for scaling up, (2-b) implementation of key success factors and lessons learnt, including emerging technologies for individualised and predictive medicine. This strategy has already been applied to the chronic respiratory disease action plan of the European Innovation Partnership on Active and Healthy Ageing.

17.
J Plast Reconstr Aesthet Surg ; 69(2): 211-20, 2016 Feb.
Article in English | MEDLINE | ID: mdl-26776905

ABSTRACT

INTRODUCTION: Immediate breast reconstruction (IBR) with implants is the commonest method of reconstructive surgery after mastectomy. With careful patient selection, a stable implant pocket can be created at the primary operation to decrease the likelihood of further surgery to adjust the reconstructed side. One-stage IBR is cost effective but failed procedures requiring early revision may be costly as permanent expanders are expensive. METHODS: Data were prospectively collected on all women undergoing a planned one-stage immediate breast reconstruction between 1997 and 2010. All patients had a Style 150 implant (Allergan, Marlow, UK). Descriptive statistics, Kaplan-Meier plots and, where applicable, Cox Proportional Hazards Regression was used to compare outcomes between groups. RESULTS: 249 planned one-stage IBRs were performed in 193 women, median age 45 years (range 20-77) with median follow-up of 101 months (range 27-159 months). 18/193 (9%) patients required implant exchange at 12 months and 66% of patients maintained their original implants at the time of census. Implant assisted latissimus appears to be robust even when radiotherapy was delivered. Disease free survival and breast cancer mortality were as expected for the breast cancer stage treated. CONCLUSION: With careful patient selection, one-stage implant IBR using a definitive anatomical expandable implant provides good long term reconstruction and safe oncologic outcome. Direct to implant decision algorithms may be influenced by future developments in acellular dermal matrix technology, but the ability to create a single-stage stable implant pocket with good surgical technique should not be forgotten.


Subject(s)
Breast Neoplasms/surgery , Esthetics , Mammaplasty/methods , Neoplasm Recurrence, Local/epidemiology , Surgical Flaps , Tissue Expansion Devices , Adult , Aged , Breast Neoplasms/diagnosis , Breast Neoplasms/mortality , Female , Humans , Incidence , Mastectomy , Middle Aged , Neoplasm Staging , Prosthesis Design , Reoperation , Retrospective Studies , Survival Rate/trends , Time Factors , Treatment Outcome , United Kingdom/epidemiology , Young Adult
18.
Pharmacogenomics J ; 16(4): 326-35, 2016 08.
Article in English | MEDLINE | ID: mdl-26503814

ABSTRACT

Short-acting ß2-agonist bronchodilators are the most common medications used in treating chronic obstructive pulmonary disease (COPD). Genetic variants determining bronchodilator responsiveness (BDR) in COPD have not been identified. We performed a genome-wide association study (GWAS) of BDR in 5789 current or former smokers with COPD in one African-American and four white populations. BDR was defined as the quantitative spirometric response to inhaled ß2-agonists. We combined results in a meta-analysis. In the meta-analysis, single-nucleotide polymorphisms (SNPs) in the genes KCNK1 (P=2.02 × 10(-7)) and KCNJ2 (P=1.79 × 10(-7)) were the top associations with BDR. Among African Americans, SNPs in CDH13 were significantly associated with BDR (P=5.1 × 10(-9)). A nominal association with CDH13 was identified in a gene-based analysis in all subjects. We identified suggestive association with BDR among COPD subjects for variants near two potassium channel genes (KCNK1 and KCNJ2). SNPs in CDH13 were significantly associated with BDR in African Americans.The Pharmacogenomics Journal advance online publication, 27 October 2015; doi:10.1038/tpj.2015.65.


Subject(s)
Adrenergic beta-2 Receptor Agonists/therapeutic use , Bronchodilator Agents/therapeutic use , Lung/drug effects , Pharmacogenomic Variants/genetics , Pulmonary Disease, Chronic Obstructive/drug therapy , Pulmonary Disease, Chronic Obstructive/genetics , Black or African American/genetics , Aged , Cadherins/genetics , Europe , Female , Genome-Wide Association Study , Genotype , Humans , Lung/physiopathology , Male , Middle Aged , New Zealand , North America , Pharmacogenomic Testing , Phenotype , Potassium Channels, Inwardly Rectifying/genetics , Potassium Channels, Tandem Pore Domain/genetics , Pulmonary Disease, Chronic Obstructive/diagnosis , Pulmonary Disease, Chronic Obstructive/physiopathology , Risk Factors , Sarcoglycans/genetics , Severity of Illness Index , Spirometry , Treatment Outcome , White People/genetics
19.
Diabet Med ; 33(5): 655-62, 2016 May.
Article in English | MEDLINE | ID: mdl-26333026

ABSTRACT

AIMS: To assess inappropriate prescribing in older people with diabetes mellitus during the month prior to a hospitalization, using tools on potentially inappropriate medicines (PIMs) and potential prescribing omissions (PPOs) and comparing inappropriate prescribing in patients with without diabetes. METHODS: In an observational, prospective multicentric study, we assessed inappropriate prescribing in 672 patients aged 75 years and older during hospital admission. The Beers, Screening Tool of Older Person's Prescriptions (STOPP) and Screening Tool to Alert Doctors to Right Treatment (START) criteria and Assessing Care of Vulnerable Elders (ACOVE-3) medicine quality indicators were used. We analysed demographic and clinical factors associated with inappropriate prescribing. RESULTS: Of 672 patients, 249 (mean age 82.4 years, 62.9% female) had a diagnosis of diabetes mellitus. The mean number of prescribing drugs per patient with diabetes was 12.6 (4.5) vs. 9.4 (4.3) in patients without diabetes (P < 0.001). Of those patients with diabetes, 74.2% used 10 or more medications; 54.5% of patients with diabetes had at least one Beers-listed PIM, 68.1% had at least one STOPP-listed PIM, 64.6% had at least one START-listed PPO and 62.8% had at least one ACOVE-3-listed PPO. Except for the Beers criteria, these prevalences were significantly higher in patients with diabetes than in those without. After excluding diabetes-related items from these tools, only STOPP-listed PIMs remained significantly higher among patients with diabetes (P = 0.04). CONCLUSIONS: Polypharmacy is common among older patients with diabetes mellitus. Inappropriate prescribing is higher in older patients with diabetes, even when diabetes-related treatment is excluded from the inappropriate prescribing evaluation.


Subject(s)
Aging , Diabetes Complications/drug therapy , Diabetes Mellitus, Type 2/drug therapy , Inappropriate Prescribing , Primary Health Care , Aged , Aged, 80 and over , Cohort Studies , Comorbidity , Developed Countries , Diabetes Complications/epidemiology , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/epidemiology , Electronic Health Records , Female , Hospitalization , Humans , Internal Medicine , Male , Medication Reconciliation , Polypharmacy , Prospective Studies , Spain/epidemiology
20.
Qual Life Res ; 24(10): 2345-54, 2015 Oct.
Article in English | MEDLINE | ID: mdl-25846413

ABSTRACT

PURPOSE: The COPD assessment test (CAT) is a questionnaire that assesses the impact of chronic obstructive pulmonary disease (COPD) on health status, but some patients have difficulties filling it up by themselves. We examined whether the mode of administration of the Spanish version of CAT (self vs. interviewer) influences its scores and/or psychometric properties. METHODS: Observational, prospective study in 49 Spanish centers that includes clinically stable COPD patients (n = 153) and patients hospitalized because of an exacerbation (ECOPD; n = 224). The CAT was self-administered (CAT-SA) or administered by an interviewer (CAT-IA) based on the investigator judgment of the patient's capacity. To assess convergent validity, the Saint George's Respiratory Disease Questionnaire (SGRQ) and the London Chest Activity of Daily Living (LCADL) instrument were also administered. Psychometric properties were compared across modes of administration. RESULTS: A total of 118 patients (31 %) completed the CAT-SA and 259 (69 %) CAT-IA. Multiple regression analysis showed that mode of administration did not affect CAT scores. The CAT showed excellent psychometric properties in both modes of administration. Internal consistency coefficients (Cronbach's alpha) were high (0.86 for CAT-SA and 0.85 for CAT-IA) as was test-retest reliability (intraclass correlation coefficients of 0.83 for CAT-SA and CAT-IA). Correlations with SGRQ and LCADL were moderate to strong both in CAT-SA and CAT-IA, indicating good convergent validity. Similar results were observed when testing longitudinal validity. CONCLUSIONS: The mode of administration does not influence CAT scores or its psychometric properties. Hence, both modes of administration can be used in clinical practice depending on the physician judgment of patient's capacity.


Subject(s)
Pulmonary Disease, Chronic Obstructive/diagnosis , Surveys and Questionnaires , Activities of Daily Living , Aged , Aged, 80 and over , Female , Follow-Up Studies , Health Status , Humans , Male , Middle Aged , Prospective Studies , Psychometrics/instrumentation , Quality of Life , Reproducibility of Results , Socioeconomic Factors , Spain
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