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1.
Int J Cancer ; 152(9): 1789-1803, 2023 05 01.
Artículo en Inglés | MEDLINE | ID: mdl-36541754

RESUMEN

There is a paucity of population-based data detailing the incidence and survival of patients with soft tissue sarcoma (STS), in part due to the heterogeneity of disease and changes to classification. Here, the incidence and survival of all STS subtypes registered in England between 2013 and 2017 were analysed using cancer registry data held by the National Cancer Registration and Analysis Service. Age-standardised incidence rates were calculated per 1 000 000 using the 2013 European Standard Population. Net survival was computed using Brenner's alternative method, with the Ederer II estimator. Age-specific overall survival was assessed using Kaplan-Meier. The influence of age, sex, socioeconomic deprivation and diagnostic routes on survival was assessed using Cox proportional hazards modelling. In total, 19 717 patients were diagnosed with STS, an average of 3943 patients per year and representing approximately 0.8% of malignancies. The most common histological diagnoses were Gastrointestinal Stromal Tumours (GIST), leiomyosarcoma and undifferentiated sarcoma, accounting for 20.2%, 13.3% and 12.7% of all sarcomas, respectively. Five-year net survival for all malignant STS was 65.0%; and was lowest for patients with vascular tumours at 39%. Patients from most deprived cohorts had 23% greater chance of dying within 5 years than patients in least deprived areas. This population-based study has allowed us for the first time to define the incidence and survival rates of prevalent STS subtypes in England such as GIST, liposarcoma and leiomyosarcoma, as well as rare entities and groups with inferior outcome. This data is invaluable for service provision, benchmarking and addressing inequality.


Asunto(s)
Tumores del Estroma Gastrointestinal , Leiomiosarcoma , Sarcoma , Neoplasias de los Tejidos Blandos , Humanos , Incidencia , Sarcoma/patología , Neoplasias de los Tejidos Blandos/epidemiología
2.
Acta Neurochir (Wien) ; 165(2): 451-459, 2023 02.
Artículo en Inglés | MEDLINE | ID: mdl-36220949

RESUMEN

PURPOSE: Due to the risk of intracranial aneurysm (IA) recurrence and the potential requirement for re-treatment following endovascular treatment (EVT), radiological follow-up of these aneurysms is necessary. There is little evidence to guide the duration and frequency of this follow-up. The aim of this study was to establish the current practice in neurosurgical units in the UK and Ireland. METHODS: A survey was designed with input from interventional neuroradiologists and neurosurgeons. Neurovascular consultants in each of the 30 neurosurgical units providing a neurovascular service in the UK and Ireland were contacted and asked to respond to questions regarding the follow-up practice for IA treated with EVT in their department. RESULTS: Responses were obtained from 28/30 (94%) of departments. There was evidence of wide variations in the duration and frequency of follow-up, with a minimum follow-up duration for ruptured IA that varied from 18 months in 5/28 (18%) units to 5 years in 11/28 (39%) of units. Young patient age, previous subarachnoid haemorrhage and incomplete IA occlusion were cited as factors that would prompt more intensive surveillance, although larger and broad-necked IA were not followed-up more closely in the majority of departments. CONCLUSIONS: There is a wide variation in the radiological follow-up of IA treated with EVT in the UK and Ireland. Further standardisation of this aspect of patient care is likely to be beneficial, but further evidence on the behaviour of IA following EVT is required in order to inform this process.


Asunto(s)
Aneurisma Roto , Embolización Terapéutica , Procedimientos Endovasculares , Aneurisma Intracraneal , Hemorragia Subaracnoidea , Humanos , Aneurisma Intracraneal/diagnóstico por imagen , Aneurisma Intracraneal/cirugía , Estudios de Seguimiento , Irlanda , Hemorragia Subaracnoidea/diagnóstico por imagen , Hemorragia Subaracnoidea/cirugía , Embolización Terapéutica/métodos , Aneurisma Roto/cirugía , Reino Unido , Resultado del Tratamiento
3.
Br J Neurosurg ; 37(2): 163-169, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-34738491

RESUMEN

OBJECTIVE: Unruptured intracranial aneurysms (UIA) are common. For many the treatment risks outweigh their risk of subarachnoid haemorrhage and patients undergo surveillance imaging. There is little data to inform if and how to monitor UIAs resulting in widely varying practices. This study aimed to determine the current practice of unruptured UIA surveillance in the United Kingdom. METHODS: A questionnaire was designed to address the themes of surveillance protocols for UIA including when surveillance is initiated, how frequently it is performed, and when it is terminated. Additionally, how aneurysm growth is managed and how clinically meaningful growth is defined were explored. The questionnaire was distributed to members of the British Neurovascular Group using probability-based cluster and non-probability purposive sampling methods. RESULTS: Responses were received from 30 of the 30 (100.0%) adult neurosurgical units in the United Kingdom of which 27 (90.0%) routinely perform surveillance for aneurysm growth. Only four units had a unit policy. The mean patient age up to which a unit would initiate follow-up of a low-risk UIA was 65.4 ± 9.0 years. The time points at which imaging is performed varied widely. There was an even split between whether units use a fixed duration of follow-up or an age threshold for terminating surveillance. Forty percent of units will follow-up patients more than 5 years from diagnosis. The magnitude in the change in size that was felt to constitute growth ranged from 1 to 3mm. No units routinely used vessel wall imaging although 27 had access to 3T MRI capable of performing it. CONCLUSIONS: There is marked heterogeneity in surveillance practices between units in the United Kingdom. This study will help units better understand their practice relative to their peers and provide a framework forplanning further research on aneurysm growth.


Asunto(s)
Aneurisma Intracraneal , Hemorragia Subaracnoidea , Adulto , Humanos , Persona de Mediana Edad , Anciano , Aneurisma Intracraneal/diagnóstico por imagen , Aneurisma Intracraneal/cirugía , Estudios de Seguimiento , Hemorragia Subaracnoidea/diagnóstico por imagen , Hemorragia Subaracnoidea/epidemiología , Hemorragia Subaracnoidea/cirugía , Reino Unido , Encuestas y Cuestionarios
4.
Br J Haematol ; 199(5): 728-738, 2022 12.
Artículo en Inglés | MEDLINE | ID: mdl-36122574

RESUMEN

This analysis is the largest population-based study to date to provide contemporary and comprehensive epidemiological estimates of all third edition of the International Classification of Diseases for Oncology (ICD-O-3) coded Langerhans cell histiocytosis (LCH) from England. People of all ages were identified from the National Cancer Registration Dataset using ICD-O-3 morphologies 9751-9754 for neoplasms diagnosed in 2013-2019. A total of 658 patients were identified, of whom 324 (49%) were children aged <15 years. The age-standardised incidence rate was 4.46 (95% confidence interval [CI] 3.99-4.98) per million children and 1.06 (95% CI 0.94-1.18) per million adults aged ≥15 years. Prevalence of LCH was 9.95 (95% CI 9.14-10.81) per million persons at the end of 2019. The 1-year overall survival (OS) was 99% (95% CI 97%-100%) for children and 90% (95% CI 87%-93%) for adults. Those aged ≥60 years had poorer OS than those aged <15 years (hazard ratio [HR] 22.12, 95% CI 7.10-68.94; p < 0.001). People in deprived areas had lower OS than those in the least deprived areas (HR 5.36, 95% CI 1.16-24.87; p = 0.03). There will inevitably be other environmental factors and associations yet to be identified, and the continued standardised data collection will allow further evaluation of data over time. This will be increasingly important with developments in LCH management following the large collaborative international trials such as LCH IV.


Asunto(s)
Histiocitosis de Células de Langerhans , Neoplasias , Niño , Adulto , Humanos , Incidencia , Prevalencia , Histiocitosis de Células de Langerhans/epidemiología , Histiocitosis de Células de Langerhans/terapia , Sistema de Registros , Neoplasias/epidemiología
6.
Am Econ Rev ; 105(3): 1067-1104, 2015 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-25999599

RESUMEN

This paper uses the rollout of the first Community Health Centers (CHCs) to study the longer-term health effects of increasing access to primary care. Within ten years, CHCs are associated with a reduction in age-adjusted mortality rates of 2 percent among those 50 and older. The implied 7 to 13 percent decrease in one-year mortality risk among beneficiaries amounts to 20 to 40 percent of the 1966 poor/non-poor mortality gap for this age group. Large effects for those 65 and older suggest that increased access to primary care has longer-term benefits, even for populations with near universal health insurance. (JEL H75, I12, I13, I18, I32, I38, J14).


Asunto(s)
Centros Comunitarios de Salud/normas , Mortalidad , Pobreza , Anciano , Anciano de 80 o más Años , Centros Comunitarios de Salud/tendencias , Predicción , Humanos , Persona de Mediana Edad , Mortalidad/tendencias , Pobreza/estadística & datos numéricos , Pobreza/tendencias , Atención Primaria de Salud , Salud Pública , Estados Unidos
7.
FASEB J ; 27(1): 222-31, 2013 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-23047895

RESUMEN

Multiple sclerosis (MS) is a severe inflammatory and neurodegenerative disease with an autoimmune background. Despite the variety of therapeutics available against MS, the development of novel approaches to its treatment is of high importance in modern pharmaceutics. In this study, experimental autoimmune encephalomyelitis (EAE) in Dark Agouti rats has been treated with immunodominant peptides of the myelin basic protein (MBP) encapsulated in mannosylated small unilamellar vesicles. The results show that liposome-encapsulated MBP(46-62) is the most effective in reducing maximal disease score during the first attack, while MBP(124-139) and MBP(147-170) can completely prevent the development of the exacerbation stage. Both mannosylation of liposomes and encapsulation of peptides are critical for the therapeutic effect, since neither naked peptides nor nonmannosylated liposomes, loaded or empty, have proved effective. The liposome-mediated synergistic effect of the mixture of 3 MBP peptides significantly suppresses the progression of protracted EAE, with the median cumulative disease score being reduced from 22 to 14 points, compared to the placebo group; prevents the production of circulating autoantibodies; down-regulates the synthesis of Th1 cytokines; and induces the production of brain-derived neurotrophic factor in the central nervous system. Thus, the proposed formulation ameliorates EAE, providing for a less severe first attack and rapid recovery from exacerbation, and offers a promising therapeutic modality in MS treatment.


Asunto(s)
Encefalitis/prevención & control , Hipersensibilidad/prevención & control , Liposomas , Péptidos/uso terapéutico , Animales , Western Blotting , Encefalitis/etiología , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Hipersensibilidad/complicaciones , Ratones , Ratas , Resonancia por Plasmón de Superficie
8.
Lancet Reg Health Eur ; 40: 100903, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38745989

RESUMEN

Background: Second primary cancers (SPCs) after breast cancer (BC) present an increasing public health burden, with little existing research on socio-demographic, tumour, and treatment effects. We addressed this in the largest BC survivor cohort to date, using a novel linkage of National Disease Registration Service datasets. Methods: The cohort included 581,403 female and 3562 male BC survivors diagnosed between 1995 and 2019. We estimated standardized incidence ratios (SIRs) for combined and site-specific SPCs using incidences for England, overall and by age at BC and socioeconomic status. We estimated incidences and Kaplan-Meier cumulative risks stratified by age at BC, and assessed risk variation by socio-demographic, tumour, and treatment characteristics using Cox regression. Findings: Both genders were at elevated contralateral breast (SIR: 2.02 (95% CI: 1.99-2.06) females; 55.4 (35.5-82.4) males) and non-breast (1.10 (1.09-1.11) females, 1.10 (1.00-1.20) males) SPC risks. Non-breast SPC risks were higher for females younger at BC diagnosis (SIR: 1.34 (1.31-1.38) <50 y, 1.07 (1.06-1.09) ≥50 y) and more socioeconomically deprived (SIR: 1.00 (0.98-1.02) least deprived quintile, 1.34 (1.30-1.37) most). Interpretation: Enhanced SPC surveillance may benefit BC survivors, although specific recommendations require more detailed multifactorial risk and cost-benefit analyses. The associations between deprivation and SPC risks could provide clinical management insights. Funding: CRUK Catalyst Award CanGene-CanVar (C61296/A27223). Cancer Research UK grant: PPRPGM-Nov 20∖100,002. This work was supported by core funding from the NIHR Cambridge Biomedical Research Centre (NIHR203312)]. The views expressed are those of the author(s) and not necessarily those of the NIHR or the Department of Health and Social Care.

9.
J Interprof Care ; 27(5): 380-6, 2013 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-23751138

RESUMEN

Natural disasters impose a significant burden on society. Current disaster training programmes do not place an emphasis on equipping surgeons with non-technical skills for disaster response. This literature review sought to identify non-technical skills required of surgeons in disaster response through an examination of four categories of literature: "disaster"; "surgical"; "organisational management"; and "interprofessional". Literature search criteria included electronic database searches, internet searches, hand searching, ancestry searching and networking strategies. Various potential non-technical skills for surgeons in disaster response were identified including: interpersonal skills such as communication, teamwork and leadership; cognitive strategies such flexibility, adaptability, innovation, improvisation and creativity; physical and psychological self-care; conflict management, collaboration, professionalism, health advocacy and teaching. Such skills and the role of interprofessionalism should be considered for inclusion in surgical disaster response training course curricula.


Asunto(s)
Conducta Cooperativa , Desastres , Cirugía General , Relaciones Interprofesionales , Grupo de Atención al Paciente , Humanos , Estudios Interdisciplinarios
10.
J Interprof Care ; 27(2): 177-83, 2013 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-22830532

RESUMEN

Interprofessional non-technical skills for surgeons in disaster response have not yet been developed. The aims of this study were to identify the non-technical skills required of surgeons in disaster response and training for disaster response and to explore the barriers and facilitators to interprofessional practice in surgical teams responding to disasters. Twenty health professionals, with prior experience in natural disaster response or education, participated in semi-structured in-depth interviews. A qualitative matrix analysis design was used to thematically analyze the data. Non-technical skills for surgeons in disaster response identified in this study included skills for austere environments, cognitive strategies and interprofessional skills. Skills for austere environments were physical self-care including survival skills, psychological self-care, flexibility, adaptability, innovation and improvisation. Cognitive strategies identified in this study were "big picture" thinking, situational awareness, critical thinking, problem solving and creativity. Interprofessional attributes include communication, team-player, sense of humor, cultural competency and conflict resolution skills. "Interprofessionalism" in disaster teams also emerged as a key factor in this study and incorporated elements of effective teamwork, clear leadership, role adjustment and conflict resolution. The majority of participants held the belief that surgeons needed training in non-technical skills in order to achieve best practice in disaster response. Surgeons considerring becoming involved in disaster management should be trained in these skills, and these skills should be incorporated into disaster preparation courses with an interprofessional focus.


Asunto(s)
Planificación en Desastres , Cirugía General , Comunicación Interdisciplinaria , Médicos/psicología , Rol Profesional , Australia , Concienciación , Canadá , Creatividad , Humanos , Solución de Problemas , Investigación Cualitativa , Pensamiento
11.
Vaccine ; 41(15): 2524-2533, 2023 04 06.
Artículo en Inglés | MEDLINE | ID: mdl-36894395

RESUMEN

Here we report the development of a thermally stable, orally administered, candidate Zika vaccine using human serotype 5 adenovirus (AdHu5). We engineered AdHu5 to express the genes for the envelope and NS1 proteins of Zika virus. AdHu5 was formulated using a proprietary platform, OraPro, comprising a mix of sugars and modified amino acids that can overcome elevated temperatures (37 C), and an enteric coated capsule that protects the integrity of the AdHu5 from the acid in the stomach. This enables the delivery AdHu5 to the immune system of the small intestine. We show that oral delivery of AdHu5 elicited antigen-specific serum IgG immune responses in a mouse model and in a non-human primate model. Importantly, these immune responses were able reduce viral counts in mice and to prevent detectable viraemia in the non-human primates on challenge with live Zika virus. This candidate vaccine has significant advantages over many current vaccines that are maintained in a cold or ultra-cold chain and require parenteral administration.


Asunto(s)
Vacunas , Vacunas Virales , Infección por el Virus Zika , Virus Zika , Humanos , Animales , Ratones , Primates , Antígenos , Anticuerpos Antivirales , Anticuerpos Neutralizantes
12.
Eur J Cancer ; 188: 20-28, 2023 07.
Artículo en Inglés | MEDLINE | ID: mdl-37178646

RESUMEN

BACKGROUND: Consensus guidelines outline that patients with primary retroperitoneal sarcoma (RPS) should be managed within specialist sarcoma centres (SSC). There is, however, a paucity of population-based data detailing incidence and outcomes in these patients. Hence, we aimed to evaluate patterns of care among RPS patients in England and compare outcomes for those undergoing surgery in high-volume specialist sarcoma centres (HV-SSC), low-volume SSC (LV-SSC), and non-SSC (N-SSC). METHODS: Data on patients diagnosed with primary RPS between 2013 and 2018 were extracted from NHS Digital's National Cancer Registration and Analysis Service using the national cancer registration dataset. Diagnostic pathways, treatment, and survival outcomes were compared between HV-SSC, LV-SSC, and N-SSC. Uni- and multivariate analyses were calculated. RESULTS: Of 1878 patients diagnosed with RPS, 1120 (60%) underwent surgery within 12 months of diagnosis, with 847 (76%) operated on at SSC; of these, 432 patients (51%) were operated on in HV-SSC, and 415 (49%) in LV-SSC. One- and 5-year estimated overall survival (OS) rates for patients undergoing surgery in N-SSC were 70.6% (95% confidence interval [CI]: 64.8-75.7) and 42.0% (CI: 35.9-47.9), compared to 85.0% (CI: 81.1-88.1) and 51.7% (CI: 46.6-56.6) in LV-SSC (p < 0.01), and 87.4% (CI: 83.9-90.2) and 62.8% (CI: 57.9-67.4) in HV-SSC, (p < 0.01). After adjusting for patient- and treatment-related factors, patients treated in HV-SSC were found to have significantly longer OS than those treated at LV-SSC, with an adjusted hazard ratio of 0.78 (CI: 0.62-0.96, p < 0.05). CONCLUSION: Patients with RPS undergoing surgery in HV-SSC have significantly better survival outcomes than those treated in N-SSC and L-SSC.


Asunto(s)
Neoplasias Retroperitoneales , Sarcoma , Neoplasias de los Tejidos Blandos , Humanos , Sarcoma/cirugía , Neoplasias Retroperitoneales/cirugía , Modelos de Riesgos Proporcionales , Inglaterra/epidemiología , Estudios Retrospectivos , Tasa de Supervivencia
13.
BMJ Open ; 13(3): e070504, 2023 03 16.
Artículo en Inglés | MEDLINE | ID: mdl-36927598

RESUMEN

INTRODUCTION: Unruptured intracranial aneurysms (UIA) are common in the adult population, but only a relatively small proportion will rupture. It is therefore essential to have accurate estimates of rupture risk to target treatment towards those who stand to benefit and avoid exposing patients to the risks of unnecessary treatment. The best available UIA natural history data are the PHASES study. However, this has never been validated and given the known heterogeneity in the populations, methods and biases of the constituent studies, there is a need to do so. There are also many potential predictors not considered in PHASES that require evaluation, and the estimated rupture risk is largely based on short-term follow-up (mostly 1 year). The aims of this study are to: (1) test the accuracy of PHASES in a UK population, (2) evaluate additional predictors of rupture and (3) assess long-term UIA rupture rates. METHODS AND ANALYSIS: The Risk of Aneurysm Rupture study is a longitudinal multicentre study that will identify patients with known UIA seen in neurosurgery units. Patients will have baseline demographics and aneurysm characteristics collected by their neurosurgery unit and then a single aggregated national cohort will be linked to databases of hospital admissions and deaths to identify all patients who may have subsequently suffered a subarachnoid haemorrhage. All matched admissions and deaths will be checked against medical records to confirm the diagnosis of aneurysmal subarachnoid haemorrhage. The target sample size is 20 000 patients. The primary outcome will be aneurysm rupture resulting in hospital admission or death. Cox regression models will be built to test each of the study's aims. ETHICS AND DISSEMINATION: Ethical approval has been given by South Central Hampshire A Research Ethics Committee (21SC0064) and Confidentiality Advisory Group support (21CAG0033) provided under Section 251 of the NHS Act 2006. The results will be disseminated in peer-reviewed journals. TRIAL REGISTRATION NUMBER: ISRCTN17658526.


Asunto(s)
Aneurisma Roto , Aneurisma Intracraneal , Hemorragia Subaracnoidea , Adulto , Humanos , Aneurisma Intracraneal/cirugía , Hemorragia Subaracnoidea/etiología , Hemorragia Subaracnoidea/epidemiología , Factores de Riesgo , Aneurisma Roto/epidemiología , Reino Unido/epidemiología , Estudios Multicéntricos como Asunto
14.
BMJ Open ; 13(8): e075187, 2023 08 09.
Artículo en Inglés | MEDLINE | ID: mdl-37558454

RESUMEN

INTRODUCTION: The top research priority for cavernoma, identified by a James Lind Alliance Priority setting partnership was 'Does treatment (with neurosurgery or stereotactic radiosurgery) or no treatment improve outcome for people diagnosed with a cavernoma?' This pilot randomised controlled trial (RCT) aims to determine the feasibility of answering this question in a main phase RCT. METHODS AND ANALYSIS: We will perform a pilot phase, parallel group, pragmatic RCT involving approximately 60 children or adults with mental capacity, resident in the UK or Ireland, with an unresected symptomatic brain cavernoma. Participants will be randomised by web-based randomisation 1:1 to treatment with medical management and with surgery (neurosurgery or stereotactic radiosurgery) versus medical management alone, stratified by prerandomisation preference for type of surgery. In addition to 13 feasibility outcomes, the primary clinical outcome is symptomatic intracranial haemorrhage or new persistent/progressive focal neurological deficit measured at 6 monthly intervals. An integrated QuinteT Recruitment Intervention (QRI) evaluates screening logs, audio recordings of recruitment discussions, and interviews with recruiters and patients/parents/carers to identify and address barriers to participation. A Patient Advisory Group has codesigned the study and will oversee its progress. ETHICS AND DISSEMINATION: This study was approved by the Yorkshire and The Humber-Leeds East Research Ethics Committee (21/YH/0046). We will submit manuscripts to peer-reviewed journals, describing the findings of the QRI and the Cavernomas: A Randomised Evaluation (CARE) pilot trial. We will present at national specialty meetings. We will disseminate a plain English summary of the findings of the CARE pilot trial to participants and public audiences with input from, and acknowledgement of, the Patient Advisory Group. TRIAL REGISTRATION NUMBER: ISRCTN41647111.


Asunto(s)
Neurocirugia , Radiocirugia , Adulto , Niño , Humanos , Estudios de Factibilidad , Proyectos Piloto , Encéfalo , Ensayos Clínicos Controlados Aleatorios como Asunto
15.
BMJ Mil Health ; 168(1): 95-98, 2022 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-33741717

RESUMEN

Armed Forces veterans (AFVs) are first and foremost citizens of the UK and are therefore-like all UK residents-entitled to universal healthcare, free at the point of need. This means that AFVs have nearly all their healthcare needs met by the NHS, which provides access to a full range of generic services. However, since 2013 there has been an Armed Forces team that can also support veterans. This review is an assessment of the work of this group over the last eight years. The health needs of AFVs have been investigated and are not significantly different from those of their demographically matched peers. However, due to their demographics, selection at recruitment and their roles, AFVs compared with the general population are more likely to be male, white and old and have fewer pre-existing or hereditary conditions. However, they do suffer from higher rates of musculoskeletal injury, different patterns of mental health illness and have historically been higher users-and abusers-of alcohol and tobacco. In addition to supporting mainstream services used by AFVs, the NHS in England commissions a bespoke range-specific 'Priority' NHS services such as those for mental health or for rehabilitation of veterans using prostheses. New interventions are continuing to be developed to improve AFVs' healthcare and are aligned to the NHS Long Term Plan and the restoration and recovery plans after the COVID-19 pandemic.


Asunto(s)
COVID-19 , Veteranos , Inglaterra , Femenino , Humanos , Masculino , Pandemias , SARS-CoV-2 , Medicina Estatal
16.
Front Immunol ; 12: 729837, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34603305

RESUMEN

We have developed a dual-antigen COVID-19 vaccine incorporating genes for a modified SARS-CoV-2 spike protein (S-Fusion) and the viral nucleocapsid (N) protein with an Enhanced T-cell Stimulation Domain (N-ETSD) to increase the potential for MHC class II responses. The vaccine antigens are delivered by a human adenovirus serotype 5 platform, hAd5 [E1-, E2b-, E3-], previously demonstrated to be effective in the presence of Ad immunity. Vaccination of rhesus macaques with the hAd5 S-Fusion + N-ETSD vaccine by subcutaneous prime injection followed by two oral boosts elicited neutralizing anti-S IgG and T helper cell 1-biased T-cell responses to both S and N that protected the upper and lower respiratory tracts from high titer (1 x 106 TCID50) SARS-CoV-2 challenge. Notably, viral replication was inhibited within 24 hours of challenge in both lung and nasal passages, becoming undetectable within 7 days post-challenge.


Asunto(s)
Vacunas contra la COVID-19/inmunología , COVID-19/prevención & control , Proteínas de la Nucleocápside de Coronavirus/inmunología , SARS-CoV-2/inmunología , Glicoproteína de la Espiga del Coronavirus/inmunología , Adenovirus Humanos/genética , Adenovirus Humanos/inmunología , Adenovirus Humanos/metabolismo , Administración Oral , Animales , Anticuerpos Neutralizantes/sangre , Anticuerpos Antivirales/sangre , Vacunas contra la COVID-19/administración & dosificación , Citocinas/sangre , Inmunización Secundaria/métodos , Inmunoglobulina G/sangre , Pulmón/virología , Macaca mulatta , Nariz/virología , Fosfoproteínas/inmunología , Dominios Proteicos/inmunología , Linfocitos T Colaboradores-Inductores/inmunología , Vacunación , Replicación Viral/inmunología
17.
Ann Surg ; 252(6): 959-65, 2010 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-21107105

RESUMEN

OBJECTIVE: To determine whether paramedic rapid sequence intubation in patients with severe traumatic brain injury (TBI) improves neurologic outcomes at 6 months compared with intubation in the hospital. BACKGROUND: Severe TBI is associated with a high rate of mortality and long-term morbidity. Comatose patients with TBI routinely undergo endo-tracheal intubation to protect the airway, prevent hypoxia, and control ventilation. In many places, paramedics perform intubation prior to hospital arrival. However, it is unknown whether this approach improves outcomes. METHODS: In a prospective, randomized, controlled trial, we assigned adults with severe TBI in an urban setting to either prehospital rapid sequence intubation by paramedics or transport to a hospital emergency department for intubation by physicians. The primary outcome measure was the median extended Glasgow Outcome Scale (GOSe) score at 6 months. Secondary end-points were favorable versus unfavorable outcome at 6 months, length of intensive care and hospital stay, and survival to hospital discharge. RESULTS: A total of 312 patients with severe TBI were randomly assigned to paramedic rapid sequence intubation or hospital intubation. The success rate for paramedic intubation was 97%. At 6 months, the median GOSe score was 5 (interquartile range, 1-6) in patients intubated by paramedics compared with 3 (interquartile range, 1-6) in the patients intubated at hospital (P = 0.28).The proportion of patients with favorable outcome (GOSe, 5-8) was 80 of 157 patients (51%) in the paramedic intubation group compared with 56 of 142 patients (39%) in the hospital intubation group (risk ratio, 1.28; 95% confidence interval, 1.00-1.64; P = 0.046). There were no differences in intensive care or hospital length of stay, or in survival to hospital discharge. CONCLUSIONS: In adults with severe TBI, prehospital rapid sequence intubation by paramedics increases the rate of favorable neurologic outcome at 6 months compared with intubation in the hospital.


Asunto(s)
Lesiones Encefálicas , Intubación Intratraqueal/métodos , Adolescente , Adulto , Lesiones Encefálicas/complicaciones , Lesiones Encefálicas/terapia , Servicios Médicos de Urgencia , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Recuperación de la Función , Adulto Joven
18.
Br J Radiol ; 93(1110): 20200020, 2020 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-32228302

RESUMEN

OBJECTIVE: We report a novel method to provide excellent anatomical depiction of a dural arteriovenous fistula (dAVF) for surgical planning. METHODS: A 78-year-old female presented with progressive back pain, deteriorating mobility and urinary incontinence with a background of obesity and severe osteoarthritis. Initial MRI suspected dAVF and subsequent spinal angiography encountered an extremely tortuous and arteriosclerotic aorta, hence catheterisation of the segmental-intercostal and lumbar vessels proved challenging. Contrast injection into the aortic arch via a pigtail catheter for arterial-phase CT angiogram of the descending aorta was performed. RESULTS: This modality of imaging delineated the dAVF showing extensive involvement of the whole spine accounting for the patient's symptoms. Furthermore this allowed characterisation of bony anatomy in relation to the fistula facilitating precise surgical approach. The dAVF was successfully disconnected through a localised laminectomy centred over the lesion. CONCLUSION: This specific technique for dAVF characterisation has not been previously reported, although trans-venous angiography has been used to some effect. In view of diagnostic and therapeutic technical difficulties that are often faced in such patients, this technique may be a useful alternative that is not only helpful in accurate diagnosis but helps in providing an invaluable guide for the surgical approach. ADVANCES IN KNOWLEDGE: This case highlights the difficulties that one may be faced within cases of tortuous vasculature and the obese patient population. With this in mind we demonstrate how a unique hybridised technique may provide valuable alternative to the neurosciences team should such a future scenario arise.


Asunto(s)
Malformaciones Vasculares del Sistema Nervioso Central/diagnóstico por imagen , Malformaciones Vasculares del Sistema Nervioso Central/cirugía , Angiografía por Tomografía Computarizada/métodos , Anciano , Angiografía/métodos , Angiografía de Substracción Digital , Aorta Torácica/diagnóstico por imagen , Malformaciones Vasculares del Sistema Nervioso Central/complicaciones , Medios de Contraste/administración & dosificación , Femenino , Humanos , Imagen por Resonancia Magnética , Obesidad/complicaciones
19.
World Neurosurg ; 144: e541-e545, 2020 12.
Artículo en Inglés | MEDLINE | ID: mdl-32891853

RESUMEN

OBJECTIVES: Accurate placement of the pedicle screw is requisite for any successful spinal instrumentation procedure. Screw insertion can be achieved using free-hand and fluoroscopic- or navigation-guided techniques. We sought to assess the variation in accuracy between fluoroscopic- and navigation-guided techniques, which are both used in Sheffield Teaching Hospitals National Health Service Trust, a tertiary spine referral center. METHODS: Using a retrospective study design, we assessed all the pedicle screws placed between 2013 and 2018. Radiographic and clinical assessment of all cases was performed. RESULTS: We studied 176 spinal instrumented cases, with a total of 831 screws implanted, out of which 296 (35.6%) were navigated and 535 (64.4%) were fluoroscopic guided. Pathology treated included spinal stenosis, spondylolisthesis, tumors, and trauma. Suboptimal screw position was identified in 2.03% (n = 6) of the navigation-guided series and 4.11% (n = 22) of the fluoroscopic-guided series with an overall screw misplacement rate of 3.4%. Evaluating surgeons' individual accuracy rates revealed that suboptimal screw placement registered a higher variation for the fluoroscopy-guided technique, and the misplacement rate was higher for surgeons with a lower volume of cases. CONCLUSIONS: Use of navigation during spinal instrumentation helps lower the rate of screw misplacement for spinal surgeons who are at the beginning of their learning curve or do not frequently perform this kind of procedure. Navigation-guided spinal instrumentation is more accurate compared with fluoroscopic-guided techniques and appears to have a lower complication rate.


Asunto(s)
Fluoroscopía/métodos , Neuronavegación/métodos , Tornillos Pediculares , Fusión Vertebral/métodos , Cirugía Asistida por Computador/métodos , Humanos , Curva de Aprendizaje , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Reoperación/estadística & datos numéricos , Estudios Retrospectivos , Enfermedades de la Columna Vertebral/cirugía , Fusión Vertebral/efectos adversos
20.
Eur J Pain ; 24(9): 1687-1702, 2020 10.
Artículo en Inglés | MEDLINE | ID: mdl-32621321

RESUMEN

BACKGROUND: Spinal manipulative therapy (SMT) is frequently used to manage cervicogenic headache (CGHA). No meta-analysis has investigated the effectiveness of SMT exclusively for CGHA. OBJECTIVE: To evaluate the effectiveness of SMT for CGHA. DATABASES AND DATA TREATMENT: Five databases identified randomized controlled trials comparing SMT with other manual therapies. The PEDro scale assessed the risk-of-bias. Pain and disability data were extracted and converted to a common scale. A random effects model was used for several follow-up periods. GRADE described the quality of evidence. RESULTS: Seven trials were eligible. At short-term follow-up, there was a significant, small effect favouring SMT for pain intensity (mean difference [MD] -10.88 [95% CI, -17.94, -3.82]) and small effects for pain frequency (standardized mean difference [SMD] -0.35 [95% CI, -0.66, -0.04]). There was no effect for pain duration (SMD - 0.08 [95% CI, -0.47, 0.32]). There was a significant, small effect favouring SMT for disability (MD - 13.31 [95% CI, -18.07, -8.56]). At intermediate follow-up, there was no significant effects for pain intensity (MD - 9.77 [-24.21 to 4.68]) and a significant, small effect favouring SMT for pain frequency (SMD - 0.32 [-0.63 to - 0.00]). At long-term follow-up, there was no significant effects for pain intensity (MD - 0.76 [-5.89 to 4.37]) and for pain frequency (SMD - 0.37 [-0.84 to 0.10]). CONCLUSION: For CGHA, SMT provides small, superior short-term benefits for pain intensity, frequency and disability, but not pain duration, however, high-quality evidence in this field is lacking. The long-term impact is not significant. SIGNIFICANCE: CGHA are a common headache disorder. SMT can be considered an effective treatment modality, with this review suggesting it providing superior, small, short-term effects for pain intensity, frequency and disability when compared with other manual therapies. These findings may help clinicians in practice better understand the treatment effects of SMT alone for CGHA.


Asunto(s)
Manipulación Espinal , Cefalea Postraumática , Humanos , Cefalea Postraumática/terapia , Resultado del Tratamiento
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