RESUMEN
Neutrophil extracellular traps contribute to lung injury in cystic fibrosis and asthma, but the mechanisms are poorly understood. We sought to understand the impact of human NETs on barrier function in primary human bronchial epithelial and a human airway epithelial cell line. We demonstrate that NETs disrupt airway epithelial barrier function by decreasing transepithelial electrical resistance and increasing paracellular flux, partially by NET-induced airway cell apoptosis. NETs selectively impact the expression of tight junction genes claudins 4, 8 and 11. Bronchial epithelia exposed to NETs demonstrate visible gaps in E-cadherin staining, a decrease in full-length E-cadherin protein and the appearance of cleaved E-cadherin peptides. Pretreatment of NETs with alpha-1 antitrypsin (A1AT) inhibits NET serine protease activity, limits E-cadherin cleavage, decreases bronchial cell apoptosis and preserves epithelial integrity. In conclusion, NETs disrupt human airway epithelial barrier function through bronchial cell death and degradation of E-cadherin, which are limited by exogenous A1AT.
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Asma , Trampas Extracelulares , Humanos , Trampas Extracelulares/metabolismo , Asma/metabolismo , Bronquios , Línea Celular , Cadherinas/metabolismoRESUMEN
BACKGROUND: Psoriatic arthritis (PsA) is a progressive and often destructive joint disease affecting approximately 20% of people with psoriasis. OBJECTIVES: To investigate associations between obesity, changes in body mass index (BMI), alcohol intake and smoking status and the development of PsA in people with psoriasis. METHODS: We undertook a cohort study involving incident cases of psoriasis identified from the U.K. Clinical Practice Research Datalink between 1998 and 2014. The associations between smoking, alcohol and BMI and development of PsA were assessed using generalized additive models. Additionally, the risks associated with a change in BMI during follow-up were investigated using distributed lag nonlinear models. RESULTS: We identified 90 189 incident cases of psoriasis (42% male, mean age 51 years), of whom 1409 had a subsequent record of PsA diagnosis. BMIs of 25·0-29·9, 30·0-34·9 and ≥ 35·0 kg m-2 were significantly associated with an increased risk of developing PsA compared with BMIs < 25·0 kg m-2 : adjusted odds ratios (95% confidence intervals) 1·79 (1·46-2·19), 2·10 (1·67-2·63) and 2·68 (2·09-3·43), respectively. Reducing BMI over a 10-year period (linearly) was associated with a reduction in the risk of developing PsA compared with BMI remaining constant over the same period. Increased risks of developing PsA were associated with moderate drinking but not with former or heavy drinking or with current or past smoking status. CONCLUSIONS: In this incident psoriasis cohort, increased BMI and moderate drinking, but not heavy drinking or smoking status, were associated with an increased risk of PsA in people with psoriasis. Importantly, we have shown that reducing weight may result in a reduction in the risk of developing PsA. What's already known about this topic? There is some evidence that increased body mass index is associated with an increased risk of developing psoriatic arthritis. There are conflicting results surrounding the relationship between smoking and the development of psoriatic arthritis among patients with psoriasis. What does this study add? Using a nonlinear and lagged effect of body mass index measured over time we have shown that reducing body mass index may be associated with a reduction in the risk of developing psoriatic arthritis. We have found no evidence that smoking alters the risk of developing psoriatic arthritis in patients with psoriasis.
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Artritis Psoriásica , Psoriasis , Artritis Psoriásica/epidemiología , Artritis Psoriásica/etiología , Estudios de Cohortes , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Psoriasis/complicaciones , Psoriasis/epidemiología , Factores de RiesgoRESUMEN
INTRODUCTION: Electronic healthcare data have several advantages over prospective observational studies, but the sensitivity of data on neurodevelopmental outcomes and its comparability with data generated through other methodologies is unknown. OBJECTIVES: The objectives of this study were to determine whether data from the UK Clinical Practice Research Datalink (CPRD) produces similar risk estimates to a prospective cohort study in relation to the risk of neurodevelopmental disorders (NDDs) following prenatal antiepileptic drug (AED) exposure. METHODS: A cohort of mother-child pairs of women with epilepsy (WWE) was identified in the CPRD and matched to a cohort without epilepsy. The study period ran from 1 January 2000 to 31 March 2007 and children were required to be in the CPRD at age 6 years. AED exposure during pregnancy was determined from prescription data and children with an NDD diagnosis by 6 years were identified from Read clinical codes. The prevalence and risk of NDDs was calculated for mother-child pairs in WWE stratified by AED regimen and for those without epilepsy. Comparisons were made with the results of the prospective Liverpool and Manchester Neurodevelopment Group study which completed assessment on 201 WWE and 214 without epilepsy at age 6 years. RESULTS: In the CPRD, 1018 mother-child pairs to WWE and 6048 to women without epilepsy were identified. The CPRD identified a lower prevalence of NDDs than the prospective study. In both studies, NDDs were more frequently reported in children of WWE than women without epilepsy, although the CPRD risk estimate was lower (2.16 vs. 0.96%, p < 0.001 and 7.46 vs. 1.87%, p = 0.0128). NDD prevalence differed across AED regimens but the CPRD data did not replicate the significantly higher risk of NDDs following in utero monotherapy valproate exposure (adjusted odds ratio [ORadj] 2.02, 95% confidence interval [CI] 0.52-7.86) observed in the prospective study (ORadj 6.05, 95% CI 1.65-24.53). CONCLUSION: It was possible to identify NDDs in the CPRD; however, the CPRD appears to under-record these outcomes. Larger studies are required to investigate further.
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Anticonvulsivantes/efectos adversos , Epilepsia/tratamiento farmacológico , Trastornos del Neurodesarrollo/epidemiología , Complicaciones del Embarazo/tratamiento farmacológico , Efectos Tardíos de la Exposición Prenatal/epidemiología , Adulto , Anticonvulsivantes/administración & dosificación , Estudios de Casos y Controles , Niño , Bases de Datos Factuales , Femenino , Humanos , Estudios Longitudinales , Masculino , Trastornos del Neurodesarrollo/inducido químicamente , Embarazo , Prevalencia , Estudios Prospectivos , Proyectos de Investigación , Reino Unido/epidemiologíaRESUMEN
OBJECTIVES: Most types of population-based cancer screening require repeat participation to be effective. This study investigated predictors of repeat participation in the NHS Bowel Cancer Screening Programme (BCSP). METHODS: The BCSP in England offers biennial colorectal cancer screening using a guaiac fecal occult blood test (gFOBt) from age 60-74 years. This analysis included 62,081 individuals aged 60-64 years at the time of the first invitation (R1). The main outcome was repeat participation at their second (R2) or third (R3) invitation. Behavioural measures derived from screening records included late return of the gFOBt kit, compliance with follow-up investigations and previous screening participation. Other potential predictors of repeat participation included results of individual test kit analysis (normal, weak positive, strong positive, spoilt) and the definitive result of the gFOBt screening episode (normal or abnormal). Age, sex and socioeconomic deprivation were also recorded. RESULTS: Overall repeat uptake was 86.6% in R2 and 88.6% in R3. Late return of the test kit was consistently associated with lower uptake (R2: 82.3% vs 88.6%, P<0.001; R3: 84.5% vs 90.5%, P<0.001). A definitive abnormal gFOBt result in the previous screening episode was a negative predictor of repeat uptake (R2: 61.4% vs 86.8%, P<0.001; R3: 65.7% vs 88.8%, P<0.001). Weak positive (R2: 76.9% vs 86.8%, P<0.001; R3: 81.7% vs 88.8%, P<0.05) and spoilt test kits (R2: 79.0% vs 86.6%, NS; R3: 84.2% vs 92.2%, P<0.05) were associated with lower repeat uptake, but were not consistently independent predictors in all invitation rounds or subgroups. Among those with a definitive abnormal gFOBt result, noncompliance with follow-up in a previous screening episode was also associated with lower repeat uptake (R2: 24.3% vs 67.1%, P<0.001; R3: 43.2% vs 69.9%, P<0.001). CONCLUSIONS: Behavioural markers and test results from previous screening episodes have been implicated in subsequent gFOBt uptake.
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Colonoscopía/métodos , Neoplasias Colorrectales/diagnóstico , Detección Precoz del Cáncer/métodos , Anciano , Colonoscopía/psicología , Colonoscopía/estadística & datos numéricos , Neoplasias Colorrectales/epidemiología , Neoplasias Colorrectales/psicología , Detección Precoz del Cáncer/psicología , Inglaterra/epidemiología , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
BACKGROUND: Colorectal neoplasia causes bleeding, enabling detection using Faecal Occult Blood tests (FOBt). The National Health Service (NHS) Bowel Cancer Screening Programme (BCSP) guaiac-based FOBt (gFOBt) kits contain six sample windows (or 'spots') and each kit returns either a positive, unclear or negative result. Test kits with five or six positive windows are termed 'abnormal' and the subject is referred for further investigation, usually colonoscopy. If 1-4 windows are positive, the result is initially 'unclear' and up to two further kits are submitted, further positivity leads to colonoscopy ('weak positive'). If no further blood is detected, the test is deemed 'normal' and subjects are tested again in 2 years' time. We studied the association between spot positivity % (SP%) and neoplasia. METHODS: Subjects in the Southern Hub completing the first of two consecutive episodes between April 2009 and March 2011 were studied. Each episode included up to three kits and a maximum of 18 windows (spots). For each positivity combination, the percentage of positive spots out of the total number of spots completed by an individual in a single-screening episode was derived and named 'SP%'. Fifty-five combinations of SP can occur if the position of positive/negative spots on the same test card is ignored.The proportion of individuals for whom neoplasia was identified in Episode 2 was derived for each of the 55 spot combinations. In addition, the Episode 1 spot pattern was analysed for subjects with cancer detected in Episode 2. RESULTS: During Episode 2, 284,261 subjects completed gFOBT screening and colonoscopies were performed on 3891 (1.4%) subjects. At colonoscopy, cancer was detected in 7.4% (n=286) and a further 39.8% (n=1550) had adenomas. Cancer was detected in 21.3% of subjects with an abnormal first kit (five or six positive spots) and in 5.9% of those with a weak positive test result.The proportion of cancers detected was positively correlated with SP%, with an R(2) correlation (linear) of 0.89. As the SP% increased from 11 to 100%, so the colorectal cancer (CRC) detection rate increased from 4 to 25%. At the lower SP%s, from 11to 25%, the CRC risk was relatively static at ~4%. Above an SP% of 25%, every 10-percentage points increase in the SP%, was associated with an increase in cancer detection of 2.5%. CONCLUSIONS: This study demonstrated a strong correlation between SP% and cancer detection within the NHS BCSP. At the population level, subjects' cancer risk ranged from 4 to 25% and correlated with the gFOBt spot pattern.Some subjects with an SP% of 11% proceed to colonoscopy, whereas others with an SP% of 22% do not. Colonoscopy on patients with four positive spots in kit 1 (SP% 22%) would, we estimate, detect cancer in ~4% of cases and increase overall colonoscopy volume by 6%. This study also demonstrated how screening programme data could be used to guide its ongoing implementation and inform other programmes.
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Neoplasias Colorrectales/diagnóstico , Detección Precoz del Cáncer/métodos , Sangre Oculta , Adulto , Anciano , Algoritmos , Colonoscopía , Neoplasias Colorrectales/etiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Juego de Reactivos para Diagnóstico , Estudios RetrospectivosRESUMEN
AIM: This study aims to investigate pregnancy losses in women with Type 1 or Type 2 diabetes and compare this with the general population. METHODS: Pregnancies ending between 1993 and 2006 in those with Type 1 or Type 2 diabetes were identified on the General Practice Research Database. Pregnancy losses were identified from medical records and the cohort described by their characteristics and prescribing for diabetes. RESULTS: Of 2001 pregnancies identified in women with Type 1 diabetes, 678 ended in a pregnancy loss: 19.6% were spontaneous, 9.6% were induced and 4.3% were losses for unknown reasons. In women with Type 2 diabetes, there were 240 losses in 669 pregnancies: 21.1% were spontaneous, 10.3% induced and 4.0% were losses for unknown reasons. The proportion of spontaneous losses in women with diabetes was higher than in the general population (13.2%). Women with Type 1 diabetes treated with human and analogue insulins were 60% more likely to have a delivery than a loss (odds ratio 1.6, 95% CI 1.18-2.18) compared with human insulin treatment alone, although numbers were small. CONCLUSION: We found that the proportions of spontaneous losses in women with Type 1 or Type 2 diabetes were similar at approximately 20%, which is higher than in the general population and also higher than previous studies have reported. While much emphasis has been placed on pre-conception care for women with Type 1 diabetes, the same is now needed for those with Type 2 diabetes, given the similarity in outcomes and increasing prevalence of this condition.
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Aborto Espontáneo/epidemiología , Glucemia/metabolismo , Diabetes Mellitus Tipo 1/complicaciones , Diabetes Mellitus Tipo 2/complicaciones , Hemoglobina Glucada/metabolismo , Complicaciones del Embarazo/epidemiología , Embarazo en Diabéticas , Aborto Inducido/estadística & datos numéricos , Adolescente , Adulto , Anomalías Congénitas/epidemiología , Diabetes Mellitus Tipo 1/sangre , Diabetes Mellitus Tipo 1/epidemiología , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/epidemiología , Consejo Dirigido , Femenino , Muerte Fetal , Humanos , Recién Nacido , Educación del Paciente como Asunto , Embarazo , Complicaciones del Embarazo/sangre , Resultado del Embarazo , Atención Primaria de Salud , Factores de Riesgo , Mortinato , Reino Unido/epidemiologíaRESUMEN
BACKGROUND: Bowel cancer is a serious health burden and its early diagnosis improves survival. The Bowel Cancer Screening Programme (BCSP) in England screens with the Faecal Occult Blood test (FOBt), followed by colonoscopy for individuals with a positive test result. Socioeconomic inequalities have been demonstrated for FOBt uptake, but it is not known whether they persist at the next stage of the screening pathway. The aim of this study was to assess the association between colonoscopy uptake and area socioeconomic deprivation, controlling for individual age and sex, and area ethnic diversity, population density, poor self-assessed health, and region. METHODS: Logistic regression analysis of colonoscopy uptake using BCSP data for England between 2006 and 2009 for 24 180 adults aged between 60 and 69 years. RESULTS: Overall colonoscopy uptake was 88.4%. Statistically significant variation in uptake is found between quintiles of area deprivation (ranging from 86.4 to 89.5%), as well as age and sex groups (87.9-89.1%), quintiles of poor self-assessed health (87.5-89.5%), non-white ethnicity (84.6-90.6%) and population density (87.9-89.3%), and geographical regions (86.4-90%). CONCLUSION: Colonoscopy uptake is high. The variation in uptake by socioeconomic deprivation is small, as is variation by subgroups of age and sex, poor self-assessed health, ethnic diversity, population density, and region.
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Neoplasias Colorrectales/diagnóstico , Neoplasias Colorrectales/economía , Detección Precoz del Cáncer/métodos , Aceptación de la Atención de Salud/estadística & datos numéricos , Anciano , Colonoscopía/economía , Colonoscopía/estadística & datos numéricos , Heces/química , Femenino , Humanos , Masculino , Persona de Mediana Edad , Programas Nacionales de Salud , Sangre Oculta , Estudios Retrospectivos , Factores de Riesgo , Factores Socioeconómicos , Tasa de Supervivencia , Reino UnidoRESUMEN
OBJECTIVE: To assess the impact of media coverage of the UK Flexible Sigmoidoscopy Trial on colorectal screening uptake in England. SETTING: In April 2010, publication of the UK Flexible Sigmoidoscopy (FS) Trial results generated considerable media interest in both FS and colorectal cancer (CRC) generally. METHODS: We used routinely collected data from the south of England (excluding London) to analyse return of faecal occult blood test (FOBt) kits within 28 days of the invitation (early uptake) among 60-69 year olds, before (T1, n = 31,229), around the time of (T2, n = 39,571), and one month after (T3, n = 33,430) the FS publicity. RESULTS: FOBt uptake over the whole period was 58.2%, with 38.4% of the kits returned within 28 days (early uptake). Across the three time periods, early uptake was 35.8% at T1, 39.4% at T2, and 39.7% at T3. Multivariate regression controlling for age, gender and socioeconomic status confirmed that uptake was higher if people received the FOBt kit around the time of the media coverage (T2: odds ratio [OR] = 1.17, 95% CI = 1.13-1.20), or one month after (T3: OR = 1.18, 95% CI = 1.15-1.22) than before (T1). Sub-group analyses demonstrated that the impact was stronger among previous non-responders than among first-time invitees or previous responders (P < 0.001). CONCLUSION: Media coverage of the FS Trial appeared to have a small but positive impact on FOBt screening uptake, especially among people who had previously abstained from screening.
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Neoplasias Colorrectales/diagnóstico , Medios de Comunicación de Masas , Sigmoidoscopía/estadística & datos numéricos , Anciano , Inglaterra , Humanos , Tamizaje Masivo/estadística & datos numéricos , Persona de Mediana EdadRESUMEN
We studied telomere length in the peripheral blood leukocyte samples of a large group of patients with chronic myelogenous leukemia (CML) by Southern blot hybridization using the (TTAGGG)4 probe. The average telomere length expressed as the peak telomere repeat array (TRA) of the peripheral blood samples obtained from a group of 34 healthy age-matched controls ranged between 7.6 and 10.0 kb and the mean peak TRA was 8.7 kb. Forty-one patients in the chronic phase of CML were studied; 32/41 (78%) showed telomere reduction (<7.6 kb) relative to age-matched controls and the mean peak TRA was 6.4 kb (range 4.0-10.6 kb). Serial samples were analysed from 12 patients at both chronic phase and during disease progression. The leukocyte DNA of all 12 patients in accelerated phase and/or blast crisis showed telomere reduction relative to age-matched controls and the mean peak TRA was 4.1 kb (range 3.0-5.4 kb). The peak TRA in the accelerated or blast phase was reduced compared with the corresponding paired sample in the chronic phase in all cases studied. These data show that a marked reduction in telomere length is associated with disease progression in CML.
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Leucemia Mielógena Crónica BCR-ABL Positiva/genética , Leucocitos/ultraestructura , Telómero/ultraestructura , Adulto , Anciano , Anciano de 80 o más Años , Crisis Blástica , Southern Blotting , Humanos , Leucemia Mielógena Crónica BCR-ABL Positiva/sangre , Persona de Mediana Edad , Secuencias Repetitivas de Ácidos NucleicosRESUMEN
A combination of focus group and individual interviews aimed to examine psychosocial aspects of nursing within a social context and social knowledge held by two teams of ward-based oncology nurses. Five core categories of knowledge emerged: knowledge of how to care, knowledge of the patient, knowledge of the ward, knowledge of nurses coping, and knowledge of involvement. Involvement or emotional closeness was seen as a necessary, inevitable and potentially stressful feature of psychosocial care. The authors conclude that interpersonal and professional aspects of nursing must be balanced in order to provide effective psychosocial care.
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Conocimientos, Actitudes y Práctica en Salud , Conocimiento , Neoplasias/enfermería , Neoplasias/psicología , Personal de Enfermería/educación , Personal de Enfermería/psicología , Enfermería Oncológica/métodos , Apoyo Social , Adaptación Psicológica , Empatía , Grupos Focales , Humanos , Relaciones Enfermero-Paciente , Investigación Metodológica en EnfermeríaRESUMEN
The concepts of the nurse as patient advocate is not new, and the evolution of this role is briefly traced in this paper as a background to presenting the findings from a small-scale qualitative study. However, whilst there is much written there is a lack of empirical work describing nurses' understandings and experiences of advocacy and what there is often derives from the USA and centres on specialized groups such as mental health, paediatric or intensive care patients or those with a learning disability. This study sought to explore understandings of the concept in a group of 15 adult nurses from general medical and surgical wards. Audiotaped semi-structured interviews were used for data collection. Data were analysed using a method appropriate for qualitative studies. Categories were generated and are presented here supported by direct participant quotes derived from the interview transcripts. These include the importance of the therapeutic relationship as the key to advocacy, nurse and patient shared common humanity, the cultural environment of care in which advocacy occurs and descriptions of 'reactive' and 'proactive' levels of advocacy.
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Actitud del Personal de Salud , Perfil Laboral , Rol de la Enfermera , Personal de Enfermería en Hospital/psicología , Defensa del Paciente , Adulto , Empatía , Ética en Enfermería , Femenino , Humanismo , Humanos , Masculino , Persona de Mediana Edad , Modelos de Enfermería , Relaciones Enfermero-Paciente , Investigación Metodológica en Enfermería , Cultura Organizacional , Derechos del Paciente , Investigación Cualitativa , Investigación , Encuestas y CuestionariosRESUMEN
This paper describes a small research study designed to explore the role of the dissertation supervisor and to examine the potential of using reflection as a tool for learning and for enhancing professional educational practice. The authors met to discuss and reflect upon the processes of supervision and the role of the supervisor throughout the period of supervising three dissertation students. Each author maintained individual reflective written accounts of supervisory meetings with students. These accounts and the transcribed tape-recordings of the group meetings provided two sets of data which were analysed using qualitative techniques. From the data analysis the authors were able to identify various phases in dissertation supervision--partnership; setting the learning contract; signposting; ownership of the dissertation; letting go; the rush at the end; maintaining the balance--and also contextual issues of humanness; time; and energy, which were needed to sustain the supervisory processes. The role of the dissertation supervisor was illuminated and the potential of using reflection as a tool for developing professional educational practice was realized. The importance of constructive support while engaged in processes of reflection cannot be underestimated.