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1.
Int J Mol Sci ; 24(6)2023 Mar 20.
Artículo en Inglés | MEDLINE | ID: mdl-36982943

RESUMEN

Colorectal cancers are one of the most prevalent tumour types worldwide and, despite the emergence of targeted and biologic therapies, have among the highest mortality rates. The Personalized OncoGenomics (POG) program at BC Cancer performs whole genome and transcriptome analysis (WGTA) to identify specific alterations in an individual's cancer that may be most effectively targeted. Informed using WGTA, a patient with advanced mismatch repair-deficient colorectal cancer was treated with the antihypertensive drug irbesartan and experienced a profound and durable response. We describe the subsequent relapse of this patient and potential mechanisms of response using WGTA and multiplex immunohistochemistry (m-IHC) profiling of biopsies before and after treatment from the same metastatic site of the L3 spine. We did not observe marked differences in the genomic landscape before and after treatment. Analyses revealed an increase in immune signalling and infiltrating immune cells, particularly CD8+ T cells, in the relapsed tumour. These results indicate that the observed anti-tumour response to irbesartan may have been due to an activated immune response. Determining whether there may be other cancer contexts in which irbesartan may be similarly valuable will require additional studies.


Asunto(s)
Antihipertensivos , Neoplasias Colorrectales , Humanos , Irbesartán/uso terapéutico , Antihipertensivos/uso terapéutico , Linfocitos T CD8-positivos/patología , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/patología
2.
Eur J Public Health ; 33(1): 6-12, 2023 02 03.
Artículo en Inglés | MEDLINE | ID: mdl-36283695

RESUMEN

BACKGROUND: Informal educational programmes focused on youth development appear to improve health and well-being at time of involvement. Less is known about long-term effects. We investigate their impact on self-reported general health in mid-life using the Aberdeen Children of the 1950s (ACONF) cohort. METHODS: We use a subset (n = 1333) of the ACONF cohort, born 1950-56, in Aberdeen Scotland, who took part in Family and Reading Surveys in 1964 and a follow-up questionnaire in 2001. We explore exposure to youth development focused clubs in childhood on self-reported general health around age 50 mediated by adult socioeconomic position. Logistic regression and mediation analysis were used to report odds ratios and natural direct and indirect effects, respectively, on multiply imputed data. RESULTS: Being a member of the Scouts/Guides (G&S) was associated with a 53% (95% confidence interval 1.03-2.27) higher odds of 'excellent' general health in adulthood compared to children attending 'other clubs'. Indirect effects of G&S and Boys'/Girls' Brigade (B&GB) on general health acting via higher socioeconomic position show positive associations; 12% and 6% higher odds of 'excellent' general health in adulthood compared to children attending 'other clubs', respectively. Comparison of indirect with direct effects suggests 27% of this association is mediated through a higher adult socioeconomic position in adulthood. CONCLUSIONS: These results suggest a beneficial association between attending G&S and B&GB clubs in childhood and adult general health. As these organizations are volunteer-led, this may represent a cost-effective method for improving population health.


Asunto(s)
Movilidad Social , Masculino , Adulto , Niño , Femenino , Humanos , Persona de Mediana Edad , Adolescente , Estudios Prospectivos , Escocia/epidemiología , Encuestas y Cuestionarios , Autoinforme , Factores Socioeconómicos
3.
Ann Oncol ; 33(9): 939-949, 2022 09.
Artículo en Inglés | MEDLINE | ID: mdl-35691590

RESUMEN

BACKGROUND: Recent advances are enabling delivery of precision genomic medicine to cancer clinics. While the majority of approaches profile panels of selected genes or hotspot regions, comprehensive data provided by whole-genome and transcriptome sequencing and analysis (WGTA) present an opportunity to align a much larger proportion of patients to therapies. PATIENTS AND METHODS: Samples from 570 patients with advanced or metastatic cancer of diverse types enrolled in the Personalized OncoGenomics (POG) program underwent WGTA. DNA-based data, including mutations, copy number and mutation signatures, were combined with RNA-based data, including gene expression and fusions, to generate comprehensive WGTA profiles. A multidisciplinary molecular tumour board used WGTA profiles to identify and prioritize clinically actionable alterations and inform therapy. Patient responses to WGTA-informed therapies were collected. RESULTS: Clinically actionable targets were identified for 83% of patients, of which 37% of patients received WGTA-informed treatments. RNA expression data were particularly informative, contributing to 67% of WGTA-informed treatments; 25% of treatments were informed by RNA expression alone. Of a total 248 WGTA-informed treatments, 46% resulted in clinical benefit. RNA expression data were comparable to DNA-based mutation and copy number data in aligning to clinically beneficial treatments. Genome signatures also guided therapeutics including platinum, poly-ADP ribose polymerase inhibitors and immunotherapies. Patients accessed WGTA-informed treatments through clinical trials (19%), off-label use (35%) and as standard therapies (46%) including those which would not otherwise have been the next choice of therapy, demonstrating the utility of genomic information to direct use of chemotherapies as well as targeted therapies. CONCLUSIONS: Integrating RNA expression and genome data illuminated treatment options that resulted in 46% of treated patients experiencing positive clinical benefit, supporting the use of comprehensive WGTA profiling in clinical cancer care.


Asunto(s)
Neoplasias , Perfilación de la Expresión Génica , Genómica/métodos , Humanos , Mutación , Neoplasias/tratamiento farmacológico , Neoplasias/genética , Medicina de Precisión/métodos , ARN , Transcriptoma
4.
Phys Rev Lett ; 125(7): 073602, 2020 Aug 14.
Artículo en Inglés | MEDLINE | ID: mdl-32857544

RESUMEN

We show that two-time, second-order correlations of scattered photons from planar arrays and chains of atoms display nonclassical features that can be described by a superatom picture of the canonical single-atom g_{2}(τ) resonance fluorescence result. For the superatom, the single-atom linewidth is replaced by the linewidth of the underlying collective low light-intensity eigenmode. Strong light-induced dipole-dipole interactions lead to a correlated response, suppressed joint photon detection events, and dipole blockade that inhibits multiple excitations of the collective atomic state. For targeted subradiant modes, the nonclassical nature of emitted light can be dramatically enhanced even compared with that of a single atom.

5.
Aliment Pharmacol Ther ; 48(3): 347-357, 2018 08.
Artículo en Inglés | MEDLINE | ID: mdl-29920726

RESUMEN

BACKGROUND: Fibrotic stricture is a common complication of Crohn's disease (CD) affecting approximately half of all patients. No specific anti-fibrotic therapies are available; however, several therapies are currently under evaluation. Drug development for the indication of stricturing CD is hampered by a lack of standardised definitions, diagnostic modalities, clinical trial eligibility criteria, endpoints and treatment targets in stricturing CD. AIM: To standardise definitions, diagnosis and treatment targets for anti-fibrotic stricture therapies in Chron's disease. METHODS: An interdisciplinary expert panel consisting of 15 gastroenterologists and radiologists was assembled. Using modified RAND/University of California Los Angeles appropriateness methodology, 109 candidate items derived from systematic review and expert opinion focusing on small intestinal strictures were anonymously rated as inappropriate, uncertain or appropriate. Survey results were discussed as a group before a second and third round of voting. RESULTS: Fibrotic strictures are defined by the combination of luminal narrowing, wall thickening and pre-stenotic dilation. Definitions of anastomotic (at site of prior intestinal resection with anastomosis) and naïve small bowel strictures were similar; however, there was uncertainty regarding wall thickness in anastomotic strictures. Magnetic resonance imaging is considered the optimal technique to define fibrotic strictures and assess response to therapy. Symptomatic strictures are defined by abdominal distension, cramping, dietary restrictions, nausea, vomiting, abdominal pain and post-prandial abdominal pain. Need for intervention (endoscopic balloon dilation or surgery) within 24-48 weeks is considered the appropriate endpoint in pharmacological trials. CONCLUSIONS: Consensus criteria for diagnosis and response to therapy in stricturing Crohn's disease should inform both clinical practice and trial design.


Asunto(s)
Consenso , Enfermedad de Crohn/terapia , Testimonio de Experto , Obstrucción Intestinal/diagnóstico , Obstrucción Intestinal/terapia , Guías de Práctica Clínica como Asunto/normas , Cateterismo/métodos , Cateterismo/normas , Ensayos Clínicos como Asunto/normas , Ensayos Clínicos como Asunto/estadística & datos numéricos , Colon/patología , Colon/cirugía , Constricción Patológica/diagnóstico , Constricción Patológica/etiología , Constricción Patológica/terapia , Enfermedad de Crohn/complicaciones , Enfermedad de Crohn/diagnóstico , Dilatación/métodos , Dilatación/normas , Endoscopía , Fibrosis/diagnóstico , Fibrosis/etiología , Fibrosis/terapia , Humanos , Obstrucción Intestinal/clasificación , Obstrucción Intestinal/etiología , Intestino Delgado/patología , Intestino Delgado/cirugía , Estándares de Referencia
6.
Age Ageing ; 47(5): 661-670, 2018 09 01.
Artículo en Inglés | MEDLINE | ID: mdl-29668839

RESUMEN

Objective: this systematic review aimed to identify immutable and modifiable prognostic factors of functional outcomes and their proposed mechanism after hip fracture surgery. Design: systematic search of MEDLINE, Embase, CINAHL, PEDRO, OpenGrey and ClinicalTrials.gov for observational studies of prognostic factors of functional outcome after hip fracture among surgically treated adults with mean age of 65 years and older. Study selection, quality assessment, and data extraction were completed independently by two reviewers. The Quality in Prognosis Studies Tool was used for quality assessment and assigning a level of evidence to factors. Proposed mechanisms for reported associations were extracted from discussion sections. Results: from 33 studies of 9,552 patients, we identified 25 prognostic factors of functional outcome after hip fracture surgery. We organised factors into groups: demographics, injury and comorbidities, body composition, complications, and acute care. We assigned two factors a weak evidence level-anaemia and cognition. We assigned Parkinson's disease an inconclusive evidence level. We could not assign an evidence level to the remaining 22 factors due to the high risk of bias across studies. Frailty was the proposed mechanism for the association between anaemia and functional outcome. Medication management, perceived potential, complications and time to mobility were proposed as mechanisms for the association between cognition and functional outcome. Conclusion: we identified one modifiable and one immutable prognostic factor for functional outcomes after hip fracture surgery. Future research may target patients with anaemia or cognitive impairment by intervening on the prognostic factor or the underlying mechanisms.


Asunto(s)
Fijación de Fractura , Fracturas de Cadera/cirugía , Articulación de la Cadera/cirugía , Anciano , Anciano de 80 o más Años , Anemia/epidemiología , Fenómenos Biomecánicos , Disfunción Cognitiva/epidemiología , Comorbilidad , Femenino , Fijación de Fractura/efectos adversos , Estado de Salud , Fracturas de Cadera/diagnóstico por imagen , Fracturas de Cadera/epidemiología , Fracturas de Cadera/fisiopatología , Articulación de la Cadera/diagnóstico por imagen , Articulación de la Cadera/fisiopatología , Humanos , Masculino , Recuperación de la Función , Factores de Riesgo , Factores de Tiempo , Resultado del Tratamiento
7.
Phys Rev Lett ; 119(25): 255301, 2017 Dec 22.
Artículo en Inglés | MEDLINE | ID: mdl-29303307

RESUMEN

In zero magnetic field the ground-state manifold of a ferromagnetic spin-1 condensate is SO(3) and exhibits Z_{2} vortices as topological defects. We investigate the phase-ordering dynamics of this system after being quenched into this ferromagnetic phase from a zero-temperature unmagnetized phase. Following the quench, we observe the ordering of both magnetic and gauge domains. We find that these domains grow diffusively, i.e., with domain size L(t)∼t^{1/2}, and exhibit dynamic scale invariance. The coarsening dynamics progresses as Z_{2} vortices annihilate; however, we find that at finite energy a number of these vortices persist in small clumps without influencing magnetic or gauge order. We consider the influence of a small nonzero magnetic field, which reduces the ground-state symmetry, and show that this sets a critical length scale such that when the domains reach this size the system dynamically transitions in order parameter and scaling behavior from an isotropic to an anisotropic ferromagnetic superfluid.

8.
Transfus Med ; 26(4): 264-70, 2016 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-27102567

RESUMEN

OBJECTIVE: To determine the long-term survival of adult recipients (>16 years) transfused with red blood cells (RBC), platelets (PLT) and fresh frozen plasma (FFP) in England and Wales. STUDY DESIGN AND METHODS: The EASTR study (Epidemiology and Survival of Transfusion Recipients) was a national multi-centre epidemiological study with cross-sectional sampling from 29 representative hospitals in England supplied by NHS Blood and Transplant (NHSBT). Three separate groups of RBC (n = 9142), FFP (n = 4232) and PLT (3584) recipients were sampled over 1 year (1 October 2001-30 September 2002), with prospective survival monitoring for 10 years. This study presents the data for adult recipients (>16 years of age). RESULTS: The median age interquartile range (IQR) of adult transfusion recipients was RBC 70 (54-79), FFP 66 (51-76), PLT 62 (48-72). The 10-year survival for adult RBC, FFP and PLT recipients was highest for RBC recipients at 36% confidence interval (CI 35-37%, n = 8675), compared with 30% for both FFP (CI 29-32%, n = 3849) and PLT (CI 28-30%, n = 3110) recipients. In all groups, post-transfusion survival decreased with age, and a risk-adjusted analysis showed that reason for transfusion, transfusion type (surgical or medical) and cancer diagnosis (presence or absence) were all significantly associated with survival. Older patients with cancer receiving a medical rather than surgical transfusion had the highest hazard of death. CONCLUSION: This study shows that survival following transfusion in England is broadly similar to that reported in other wealthy nations. More than 70% of recipients die within 10 years of transfusion, but long-term survival is common in younger patients (>80% 10-year survival in RBC recipients aged 16-39 years).


Asunto(s)
Transfusión de Eritrocitos/mortalidad , Plasma , Transfusión de Plaquetas/mortalidad , Adolescente , Adulto , Anciano , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Tasa de Supervivencia , Factores de Tiempo
9.
Transfus Med ; 26(2): 111-7, 2016 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-26969868

RESUMEN

OBJECTIVE: To describe the epidemiology of blood transfusion in children: including the incidence of transfusion, the diagnoses leading to transfusion, donor exposure (DE) and post-transfusion survival. STUDY DESIGN AND METHODS: The Epidemiology and Survival of Transfusion Recipients (EASTR) Study was a multi-centre epidemiological study with prospective survival monitoring. Cross-sectional sampling of adult and paediatric transfusion recipients in 29 hospitals was used to select three separate cohorts of red cell (RBC), platelet (PLT) and fresh frozen plasma (FFP) recipients between October 2001 and September 2002. This paper presents the analysis of results for children <16 years. RESULTS: Children <16 years comprised 449 (5%) of the RBC, 362 (9%) of the FFP and 452 (13%) of the PLT recipients. In children 54% of RBC, 63% FFP and 45% PLT recipients were under 1 year of age and 57% RBC, 60% FFP and 52% PLT were male. Median (IQR) DEduring the study year was 3(2-8); 5(2-13) and 11(6-21) in the RBC, FFP and PLT cohorts, respectively. A total of 20% of RBC, 31% of FFP and 54% of PLT recipients had been exposed to >10 donors. Perinatal conditions were the commonest indication for transfusion in the RBC (36%) and FFP (44%) cohorts and comprised 31% of the PLT cohort. Medical conditions (48%), predominantly malignancy (33%), were the most frequent indication in the PLT cohort. The 10 year (95% CI) survival rates were 81% (77-85%), 72% (67-76%) and 71% (66-75%)for RBC, FFP and PLT cohorts, respectively. CONCLUSIONS: Around half of paediatric transfusion recipients are under 1 year of age. Exposure to components from multiple donors is common. At least 70% of paediatric recipients are long survivors and are at risk for late complications of transfusion.


Asunto(s)
Transfusión de Componentes Sanguíneos/métodos , Donantes de Sangre , Adolescente , Adulto , Niño , Preescolar , Femenino , Estudios de Seguimiento , Humanos , Lactante , Recién Nacido , Masculino , Tasa de Supervivencia
10.
Vox Sang ; 108(4): 378-86, 2015 May.
Artículo en Inglés | MEDLINE | ID: mdl-25688854

RESUMEN

BACKGROUND AND OBJECTIVES: The elements of clinical governance, which ensure excellence in clinical care, can be applied to blood services. In this survey, their application in a range of blood providers was gauged, with the aim of identifying best practice and producing a generalizable framework. MATERIALS AND METHODS: The Medical Directors of members of the Alliance of Blood Operators surveyed how different elements of clinical governance operated within their organizations and developed recommendations applicable in the blood service environment. RESULTS: The recommendations that emerged highlighted the importance of an organization's culture, with the delivery of optimal clinical governance being a corporate responsibility. Senior management must agree and promote a set of values to ensure that the system operates with the patient and donor at its heart. All staff should understand how their role fits into the 'journey to the patient', and a culture of openness promoted. Thus, reporting of errors and risks should be actively sought and praised, with penalties applied for concealment. Systems should exist to collect, analyse and escalate clinical outcomes, safety data, clinical risk assessments, incident reports and complaints to inform organizational learning. CONCLUSION: Clinical governance principles from general health care can be applied within blood services to complement good manufacturing practice. This requires leadership, accountability, an open culture and a drive for continuous improvement and excellence in clinical care.


Asunto(s)
Conservación de la Sangre/normas , Transfusión Sanguínea/normas , Gestión Clínica/estadística & datos numéricos , Calidad de la Atención de Salud , Gestión Clínica/organización & administración , Gestión Clínica/normas , Humanos
11.
West Indian Med J ; 63(1): 54-8, 2014 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-25303195

RESUMEN

OBJECTIVE: Many neurosurgical cases are done without the need for blood transfusion, yet blood is unnecessarily cross-matched, resulting in wasted resources. This study was undertaken to document and compare the number of units of blood components requested, cross-matched and transfused in neurosurgical cases at the University Hospital of the West Indies (UHWI). METHODS: A prospective, observational study was undertaken over one year. Data collected for each patient included demographic information, relevant perioperative data, and blood banking data including blood components requested, cross-matched and transfused. Data were analysed using SPSS version 16. RESULTS: Data were analysed on 152 patients, 71 females (46.7%) and 81 males (53.3%). The mean age was 48.7 ± 19.6 years and 100 of the procedures were done electively (65.8%). Blood components were ordered in 114 (75%) cases, red cells more commonly in 113 (74.3%) patients, and plasma in 19 (12.5%) patients. Overall, 20 patients (13.2%) were transfused. Most patients (90.9%) needed one to two units of blood. Of the 236 units of blood components that were cross-matched or prepared, only 62 were transfused. The cross-match/preparation to transfusion ratio (CTR/PTR) was 6.00 for red cells and 1.31 for plasma. Preoperative haemoglobin ≤ 10.0 g/dL (p = 0.001), estimated blood loss of ≥ 1 litre (p < 0.001), higher American Society of Anesthesiologists (ASA) physical status score (p < 0.03) and a resident as lead surgeon (p < 0.05), were significant predictors of blood transfusion. CONCLUSION: The transfusion rate was low with a high cross-match to transfusion ratio, suggesting that less cross-matching is needed. A new approach to blood ordering for neurosurgical cases is recommended.

13.
West Indian med. j ; 63(1): 54-58, Jan. 2014. tab
Artículo en Inglés | LILACS | ID: biblio-1045787

RESUMEN

OBJECTIVE: Many neurosurgical cases are done without the need for blood transfusion, yet blood is unnecessarily cross-matched, resulting in wasted resources. This study was undertaken to document and compare the number of units of blood components requested, cross-matched and transfused in neurosurgical cases at the University Hospital of the West Indies (UHWI). METHODS: A prospective, observational study was undertaken over one year. Data collected for each patient included demographic information, relevant perioperative data, and blood banking data including blood components requested, cross-matched and transfused. Data were analysed using SPSS version 16. RESULTS: Data were analysed on 152 patients, 71 females (46.7%) and 81 males (53.3%). The mean age was 48.7 ± 19.6 years and 100 of the procedures were done electively (65.8%). Blood components were ordered in 114 (75%) cases, red cells more commonly in 113 (74.3%) patients, and plasma in 19 (12.5%) patients. Overall, 20 patients (13.2%) were transfused. Most patients (90.9%) needed one to two units of blood. Of the 236 units of blood components that were cross-matched or prepared, only 62 were transfused. The cross-match/preparation to transfusion ratio (CTR/PTR) was 6.00 for red cells and 1.31 for plasma. Preoperative haemoglobin < 10.0 g/dL (p = 0.001), estimated blood loss of > 1 litre (p < 0.001), higher American Society of Anesthesiologists (ASA) physical status score (p < 0.03) and a resident as lead surgeon (p < 0.05), were significant predictors of blood transfusion. CONCLUSION: The transfusion rate was low with a high cross-match to transfusion ratio, suggesting that less cross-matching is needed. A new approach to blood ordering for neurosurgical cases is recommended.


OBJETIVO: Muchos casos neuroquirurgicos se realizan sin necesidad de transfusion de sangre. Sin embargo, la sangre es innecesariamente sometida a pruebas cruzadas, lo cual resulta en un malgasto de recursos. Este estudio fue emprendido con el proposito de documentar y comparar el numero de unidades de los componentes sanguineos requeridos, cotejados, y transfundidos en los casos de neurocirugia en el Hospital Universitario de West Indies (HUWI). MÉTODOS: Se realizo un estudio prospectivo observacional por espacio de mas de un ano. Los datos recopilados de cada paciente incluian informacion demografica, datos relevantes perioperatorios, y datos de bancos de sangre, incluyendo los componentes sanguineos solicitados, cotejados, y transfundidos. Los datos fueron analizados utilizando SPSS version 16. RESULTADOS: Los datos se analizaron en 152 pacientes: 71 mujeres (46.7%) y 81 varones (53.3%). La edad promedio fue de 48.7 ± 19.6 anos y 100 de los procedimientos se realizaron de manera electiva (65.8%). Se ordenaron componentes de la sangre en 114 casos (75%), siendo los globulos rojos los mas comunmente requeridos en 113 pacientes (74,3%) y el plasma en 19 pacientes (12.5%). En general, 20 pacientes (13.2%) fueron transfundidos. La mayoria de los pacientes (90.9%) necesito una o dos unidades de sangre. De las 236 unidades de componentes sanguineos que fueron preparados o sometidos a pruebas cruzadas, solo 62 fueron transfundidos. La proporcion de la preparacion/prueba cruzada en relacion con la transfusion (CTR/PTR por sus siglas en ingles) fue 6.00 para los globulos rojos y 1.31 para el plasma. La hemoglobina preoperatoria < 10.0 g/dL (p = 0.001), la perdida estimada de sangre de > 1 litro (p < 0.001), la mayor puntuacion del estado fisico (p < 0.03) segun los criterios de la Sociedad Americana de Anestesiologos (ASA), y un residente como principal cirujano (p < 0.05), fueron predictores significativos de la transfusion de sangre. CONCLUSIÓN: La tasa de transfusion fue baja, con una alta proporcion de la prueba cruzada frente a la transfusion, sugiriendo que se necesitan menos pruebas cruzadas. Se recomienda un nuevo enfoque a la hora de hacer pedidos de sangre para los casos neuroquirurgicos.


Asunto(s)
Humanos , Masculino , Femenino , Recién Nacido , Lactante , Preescolar , Niño , Adolescente , Adulto , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Transfusión Sanguínea/estadística & datos numéricos , Procedimientos Neuroquirúrgicos/métodos , Estudios Prospectivos , Hospitales Universitarios
14.
Transfus Clin Biol ; 20(4): 405-11, 2013 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-23928183

RESUMEN

Three cases of vCJD transmission by blood transfusion have been reported in the UK, and a fourth case discovered at post-mortem. Modelling has been conducted to predict the number of cases that may occur in the future through transfusion, based on estimates of prevalence, infectivity and susceptibility, and a number of steps have been taken to reduce the risk of transmission. These include deferral of previously transfused donors, leucocyte depletion of all components, importation of plasma for certain patient groups and for fractionation, and the collection of the majority of platelets from single donors (by apheresis). However, even with these interventions, some future cases are still predicted. The UK-wide Advisory Committee on the Safety of Blood, Tissues and Organs (SaBTO) considers the evidence for clinical and cost-effectiveness of any proposed intervention, such as prion assays and filters, and makes recommendations to the governments of the UK. The development of prion assays is challenging as prions do not generate an immune response, do not have nucleic acid and are present in blood in very low concentrations against a high background of normal prion protein. It is critically important that prion assays show high levels of sensitivity and - especially -specificity for a healthy blood donor population. Assessment is impacted by the very short supply of positive human samples, necessitating the use of animal models. Filters that are capable of removing prions from blood components have been developed and CE marked, but it is again necessary to use animal models to study their efficacy. Guidelines have been produced for the assessment of the quality of red cells filtered through these devices, and a clinical safety study has recently been completed. In conclusion, the evaluation of screening assays and prion filters is challenging, time-consuming and costly, but these evaluations are critical to policy making.


Asunto(s)
Seguridad de la Sangre/métodos , Síndrome de Creutzfeldt-Jakob/prevención & control , Priones/sangre , Reacción a la Transfusión , Animales , Donantes de Sangre , Seguridad de la Sangre/instrumentación , Seguridad de la Sangre/normas , Síndrome de Creutzfeldt-Jakob/epidemiología , Síndrome de Creutzfeldt-Jakob/transmisión , Modelos Animales de Enfermedad , Predicción , Política de Salud , Humanos , Tamizaje Masivo , Garantía de la Calidad de Atención de Salud , Riesgo , Sensibilidad y Especificidad , Reino Unido/epidemiología
16.
Vox Sang ; 103(2): 107-12, 2012 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-22404076

RESUMEN

BACKGROUND AND OBJECTIVES: During the 1918, pandemic blood components were successfully used to treat severe influenza pneumonia. A Proof of Principle trial investigating the clinical benefit of convalescent plasma was proposed in the 2009 H1N1v epidemic with the aim of screening donors for high titre antibody in order to stockpile plasma packs to be used for treatment for severe pneumonia. MATERIALS AND METHODS: Serum samples were collected from donors. IgG antibody capture format enzyme-linked immunoassays using recombinant proteins (GACELISAs) were compared with microneutralization (MN) and haemagglutination inhibition (HAI). The influence of age and history of influenza-like illness (ILI) on the detection of high titre antibody was examined. RESULTS: 1598 unselected donor sera collected in October and December 2009 were tested by HAI. The HAI and demographic data defined a possible strategy for selective donor screening. One of the GACELISAs was highly specific for recent infection but showed lower sensitivity than HAI. CONCLUSIONS: During the 2009 pandemic screening 17- to 30-year-old donors by HAI delivered around 10% with high antibody levels. The ELISA using a short recombinant H1N1v HA detected fewer reactives but was more specific for high titre antibody (≥1:256). Screening strategies are proposed based on using HAI on serum or GACELISA on plasma.


Asunto(s)
Anticuerpos Antivirales/sangre , Donantes de Sangre , Convalecencia , Selección de Donante/métodos , Subtipo H1N1 del Virus de la Influenza A , Gripe Humana/sangre , Gripe Humana/epidemiología , Pandemias , Adolescente , Adulto , Inglaterra/epidemiología , Femenino , Humanos , Plasma
18.
Foot (Edinb) ; 20(2-3): 71-4, 2010.
Artículo en Inglés | MEDLINE | ID: mdl-20638271

RESUMEN

BACKGROUND: Foot problems are highly prevalent in inflammatory arthritis (IA), especially rheumatoid arthritis (RA). Chronic inflammation can lead to permanent structural changes, deformity and disability. Early podiatry intervention in RA improves long term outcomes. National guidelines recommend that patients should be treated by a multidisciplinary team with dedicated podiatry services. In clinical practice funding constraints limit availability of these services. OBJECTIVES: To assess prevalence of foot problems and quality and availability of foot care services at a UK district general hospital. METHOD: 1200 IA patients in Swindon (Wiltshire, UK) were invited to complete an anonymised questionnaire regarding access to foot care services and education/information on foot problems. RESULTS: 448 patients. Prevalence of foot problems: 68%. Only 31% of patients had access to appropriate foot specialist. 24% had received foot assessment within 3 months of diagnosis of IA and 17% yearly review thereafter. CONCLUSIONS: Despite high prevalence of foot problems in our population we identified significant deficiencies in provision of integrated multidisciplinary podiatry care. The data we present could be used by others to support business cases to obtain funding to improve the links between rheumatology and podiatry services.


Asunto(s)
Artritis Reumatoide/complicaciones , Enfermedades del Pie/etiología , Enfermedades del Pie/terapia , Accesibilidad a los Servicios de Salud , Podiatría , Anciano , Artritis Psoriásica/complicaciones , Estudios Transversales , Femenino , Enfermedades del Pie/epidemiología , Encuestas de Atención de la Salud , Hospitales de Distrito/estadística & datos numéricos , Humanos , Masculino , Persona de Mediana Edad , Servicio Ambulatorio en Hospital/estadística & datos numéricos , Prevalencia , Derivación y Consulta , Espondilitis Anquilosante/complicaciones , Reino Unido/epidemiología
19.
Transfus Med ; 19(6): 315-28, 2009 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-19735383

RESUMEN

This study provides data on National Blood Service (NBS) red blood cell (RBC, n = 9142), platelet (PLT, n = 4232) and fresh frozen plasma (FFP, n = 3584) recipients independently sampled by monthly quota from 29 representative hospitals over 12 months in 2001-2002. Hospitals were stratified by size according to total yearly RBC issues. Transfusion indications were chosen from diagnostic and procedural codes, and recipients grouped into Epidemiology and Survival of Transfusion Recipients Case-mix Groups (E-CMGs). The main E-CMGs were digestive [19% of RBC recipients; including 5% gastrointestinal (GI) bleeds and 3% colorectal surgery], musculoskeletal (15%; 12% hip and knee replacement), haematology (13%) and obstetrics and gynaecology (10%). Renal failure, fractured neck of femur, cardiac artery by-pass grafting (CABG) and paediatrics, each accounted for 3-4% recipients. FFP recipients: the main E-CMGs were digestive (21% of FFP recipients; including 7% GI bleeds and 3% colorectal surgery), hepatobiliary (15%; 7% liver disease and 2% liver transplant), cardiac (12%) and paediatrics (9%) The renal, paediatrics, vascular and haematology E-CMGs each had 6-7% of recipients. PLT recipients: the main E-CMGs were haematology (27% of PLT recipients; including 9% lymphoma and 8% acute leukaemia), cardiac (17%), paediatrics (13%), hepatobiliary (10%) and digestive (9%). Back-weighting gave national estimates of 433 000 RBC, 57 500 FFP and 41 500 PLT recipients/year in England and North Wales, median age 69, 64 and 59 years, respectively. Digestive and hepatobiliary indications emerged as the top reason for transfusion in RBC and FFP recipients, and was also a frequent indication in PLT recipients.


Asunto(s)
Transfusión Sanguínea/estadística & datos numéricos , Hemorragia/terapia , Hospitales/estadística & datos numéricos , Bancos de Sangre , Inglaterra , Transfusión de Eritrocitos , Hemorragia/patología , Humanos , Plasma , Transfusión de Plaquetas , Estudios Retrospectivos , Gales
20.
Sex Transm Infect ; 85(6): 427-31, 2009 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-19525262

RESUMEN

OBJECTIVE: To examine infectious disease and AIDS mortality among African migrants in Portugal, gender and socio-economic differences in AIDS mortality risk, and differences between African migrants to Portugal and to England and Wales. METHODS: Data from death registrations, 1998-2002, and the 2001 Census were used to derive standardised death rates by country of birth, occupational class (men only), and marital status. RESULTS: Compared with people born in Portugal, African migrants had higher mortality for infectious diseases including AIDS. There was considerable heterogeneity among Africans, with those from Cape Verde having the highest mortality. Death rates were more than five times higher among those who were unmarried than those who were. A larger proportion of Africans were unmarried accounting for some excess mortality. Death rates were also higher among men from manual occupational classes than among men from non-manual. A comparison with England and Wales shows that death rates for infectious disease and AIDS in Portugal are much higher and Africans in Portugal also fare worse than Africans in England and Wales. CONCLUSION: AIDS mortality rates were higher among Africans than those born in Portugal and were associated with socio-environmental factors. Further research is required to interpret the excess mortality among Africans and there is a need to ensure the inclusion of relevant data items on ethnicity in national monitoring and surveillance systems.


Asunto(s)
Síndrome de Inmunodeficiencia Adquirida/mortalidad , Población Negra/estadística & datos numéricos , Enfermedades Transmisibles/mortalidad , Migrantes/estadística & datos numéricos , Síndrome de Inmunodeficiencia Adquirida/etnología , Adulto , África/etnología , Población Negra/etnología , Cabo Verde/etnología , Enfermedades Transmisibles/etnología , Inglaterra/epidemiología , Femenino , Humanos , Masculino , Estado Civil , Persona de Mediana Edad , Portugal/epidemiología , Factores de Riesgo , Factores Sexuales , Medio Social , Factores Socioeconómicos , Gales/epidemiología
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