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BACKGROUND: The priorities for UK emergency medicine research were defined in 2017 by a priority setting partnership coordinated by the Royal College of Emergency Medicine in collaboration with the James Lind Alliance (JLA). Much has changed in the last 5 years, not least a global infectious disease pandemic and a significant worsening of the crisis in the urgent and emergency care system. Our aim was to review and refresh the emergency medicine research priorities. METHODS: A steering group including patients, carers and healthcare professionals was established to agree to the methodology of the refresh. An independent adviser from the JLA chaired the steering group. The scope was adult patients in the ED. New questions were invited via an open call using multiple communications methods ensuring that patients, carers and healthcare professionals had the opportunity to contribute. Questions underwent minisystematic (BestBETs) review to determine if the question had been answered, and the original 2017 priorities were reviewed. Any questions that remained unanswered were included in an interim prioritisation survey, which was distributed to patients, carers and healthcare professionals. Rankings from this survey were reviewed by the steering group and a shortlist of questions put forward to the final workshop, which was held to discuss and rank the research questions in order of priority. RESULTS: 77 new questions were submitted, of which 58 underwent mini-systematic review. After this process, 49 questions (of which 32 were new, 11 were related to original priorities and 6 unanswered original priorities were carried forward) were reviewed by the steering group and included in an interim prioritisation survey. The interim prioritisation survey attracted 276 individual responses. 26 questions were shortlisted for discussion at the final prioritisation workshop, where the top 10 research priorities were agreed. CONCLUSION: We have redefined the priorities for emergency medicine research in the UK using robust and established methodology, which will inform the agenda for the coming years.
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Investigación Biomédica , Medicina de Emergencia , Adulto , Humanos , Encuestas y Cuestionarios , Personal de Salud , Pacientes , Prioridades en SaludRESUMEN
IMPORTANCE: This paper investigates the use of a major trauma prediction model in the UK setting. We demonstrate that application of this model could reduce the number of patients with major trauma being incorrectly sent to non-specialist hospitals. However, more research is needed to reduce over-triage and unnecessary transfer to Major Trauma Centres. OBJECTIVE: To externally validate the Dutch prediction model for identifying major trauma in a large unselected prehospital population of injured patients in England. DESIGN: External validation using a retrospective cohort of injured patients who ambulance crews transported to hospitals. SETTING: South West region of England. PARTICIPANTS: All patients ≥16 years with a suspected injury and transported by ambulance in the year from February 1, 2017. EXCLUSION CRITERIA: 1) Patients aged ≤15 years; 2) Non-ambulance attendance at hospital with injuries; 3) Death at the scene and; 4) Patients conveyed by helicopter. This study had a census sample of cases available to us over a one year period. INTERVENTIONS OR EXPOSURES: Tested the accuracy of the prediction model in terms of discrimination, calibration, clinical usefulness, sensitivity and specificity and under- and over triage rates compared to usual triage practices in the South West region. MAIN OUTCOME MEASURE: Major trauma defined as an Injury Severity Score>15. RESULTS: A total of 68799 adult patients were included in the external validation cohort. The median age of patients was 72 (i.q.r. 46-84); 55.5% were female; and 524 (0.8%) had an Injury Severity Score>15. The model achieved good discrimination with a C-Statistic 0.75 (95% CI, 0.73 - 0.78). The maximal specificity of 50% and sensitivity of 83% suggests the model could improve undertriage rates at the expense of increased overtriage rates compared with routine trauma triage methods used in the South West, England. CONCLUSIONS AND RELEVANCE: The Dutch prediction model for identifying major trauma could lower the undertriage rate to 17%, however it would increase the overtriage rate to 50% in this United Kingdom cohort. Further prospective research is needed to determine whether the model can be practically implemented by paramedics and is cost-effective.
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Servicios Médicos de Urgencia , Heridas y Lesiones , Adulto , Inglaterra/epidemiología , Femenino , Humanos , Puntaje de Gravedad del Traumatismo , Masculino , Estudios Retrospectivos , Centros Traumatológicos , Triaje , Reino Unido , Heridas y Lesiones/terapiaRESUMEN
BACKGROUND: The availability of resources, knowledge, and will to expand access to high-quality emergency care in low- and middle-income countries has made strong progress in recent years. While the possibility for intervention has improved, the need has only grown more pressing. What remains is for us, the people who practice and support emergency care delivery on a regular basis, to pull these elements together and present a cohesive call to action for leaders to prioritize the development of emergency care. This advocacy should coalesce around two high-level commitments: the Sustainable Development Goals and Universal Health Coverage. Emergency care has not been a traditional tool that policy makers rely on to improve health and development; however, we can show that it is actually critical to achieving these goals. Making this case has become possible with the availability of evidence that shows emergency health conditions contribute to a substantial portion of the disease burden, emergency care interventions are high-impact, and the interventions can be implemented without a substantial increase in resources. MAIN BODY: There is a growing understanding of the burden of disease in low- and middle-income countries and how 54% or 24.3 million deaths are amenable to emergency care systems. There are a group of diseases that are time sensitive and show improved outcomes with good emergency care systems. Alongside an improving scientific underpinning to emergency care, there is growing policy recognition. While there is no direct mention of emergency care in the Sustainable Development Goals document, many goals, such as reductions in infant and maternal deaths, deaths due to non-communicable diseases, road traffic injuries and violence, improving resilience of climate change, universal coverage, and safe/sustainable urban environments are not achievable without developing, sustaining, and improving the quality of emergency care systems. CONCLUSION: To take emergency care to the next level, we must capitalize on the growing understanding of the disease burden of emergent conditions, along with the increasing evidence of the high-impact and low-cost of emergency care interventions. Linking these messages to widely accepted policy priorities like the SDGs and UHC will increase attention towards the development of emergency care systems, which potentially could save lives.
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UNLABELLED: To compare frequencies of autoreactive antibody responses to endogenous disease-associated antigens in healthy controls (HC), relapsing and progressive MS and to assess their associations with clinical and MRI measures of MS disease progression. METHODS: The study analyzed 969 serum samples from 315 HC, 411 relapsing remitting MS (RR-MS), 128 secondary progressive MS (SP-MS), 33 primary progressive MS (PP-MS) and 82 patients with other neurological diseases for autoantibodies against two putative MS antigens CSF114(Glc) and KIR4.1a and KIR4.1b and against 24 key endogenous antigens linked to diseases such as vasculitis, systemic sclerosis, rheumatoid arthritis, Sjogren's syndrome, systemic lupus erythematosus, polymyositis, scleroderma, polymyositis, dermatomyositis, mixed connective tissue disease and primary biliary cirrhosis. Associations with disability and MRI measures of lesional injury and neurodegeneration were assessed. RESULTS: The frequencies of anti-KIR4.1a and anti-KIR4.1b peptide IgG positivity were 9.8% and 11.4% in HC compared to 4.9% and 7.5% in RR-MS, 8.6% for both peptides in SP-MS and 6.1% for both peptides in PP-MS (p = 0.13 for KIR4.1a and p = 0.34 for KIR4.1b), respectively. Antibodies against CSF114(Glc), KIR4.1a and KIR4.1b peptides were not associated with MS compared to HC, or with MS disease progression. HLA DRB1*15:01 positivity and anti-Epstein Barr virus antibodies, which are MS risk factors, were not associated with these putative MS antibodies. CONCLUSIONS: Antibody responses to KIR4.1a and KIR4.1b peptides are not increased in MS compared to HC nor associated with MS disease progression. The frequencies of the diverse autoreactive antibodies investigated are similar in MS and HC.
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Antígenos/sangre , Enfermedades Autoinmunes/inmunología , Esclerosis Múltiple/inmunología , Adulto , Antígenos/inmunología , Autoanticuerpos/sangre , Autoanticuerpos/inmunología , Estudios de Casos y Controles , Citomegalovirus/inmunología , Femenino , Cadenas HLA-DRB1/genética , Cadenas HLA-DRB1/inmunología , Herpesvirus Humano 4/inmunología , Humanos , Inmunidad Humoral , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Esclerosis Múltiple Recurrente-Remitente/inmunología , Canales de Potasio de Rectificación Interna/sangre , Canales de Potasio de Rectificación Interna/inmunología , Valores de ReferenciaRESUMEN
In the field of transplantation, flow cytometry serves a well-established role in pre-transplant crossmatching and monitoring immune reconstitution following hematopoietic stem cell transplantation. The capabilities of flow cytometers have continuously expanded and this combined with more detailed knowledge of the constituents of the immune system, their function and interaction and newly developed reagents to study these parameters have led to additional utility of flow cytometry-based analyses, particularly in the post-transplant setting. This review discusses the impact of flow cytometry on managing alloantigen reactions, monitoring opportunistic infections and graft rejection and gauging immunosuppression in the context of solid organ transplantation.
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Citometría de Flujo , Rechazo de Injerto/inmunología , Trasplante de Células Madre Hematopoyéticas , Tolerancia Inmunológica , Isoantígenos/inmunología , Infecciones Oportunistas/inmunología , Trasplante de Órganos , Animales , Separación Celular , Rechazo de Injerto/prevención & control , Histocompatibilidad/inmunología , Prueba de Histocompatibilidad , Humanos , Monitorización Inmunológica/métodosRESUMEN
PURPOSE: To help establish patterns of care and standards of care of interstitial permanent low-dose-rate (LDR) and temporary high-dose-rate brachytherapy for prostate cancer and to compare the results with a similar 1998 American Brachytherapy Society (ABS) survey. METHODS AND MATERIALS: A comprehensive questionnaire intended to survey specific details of current clinical brachytherapy practice was provided to the participants of the seventh ABS Prostate Brachytherapy School. Responses were tabulated and descriptive statistics are reported. RESULTS: Sixty-five brachytherapy practitioners responded to the survey. Eighty-nine percent (89%) of respondents performed LDR and 49% perform high-dose-rate brachytherapy. The median number of years of experience for LDR brachytherapists increased from 5 to 10 years over the course of the 12 years since the preceding survey. Compared with the first ABS, a smaller proportion of respondents received formal brachytherapy residency training (43% vs. 56%) or formal "hands-on" brachytherapy training (15% vs. 63%). There has been a marked decline in the utilization of the Mick applicator (Mick Radio-Nuclear Instruments, Inc., Mount Vernon, NY, USA) (60% vs. 28%) and an increase in the use of stranded seeds (40% vs. 11%). Compliance with postimplant dosimetry was higher in the 2010 survey. CONCLUSION: This survey does suggest an evolution in the practice of LDR brachytherapy since 1998 and aids in identifying aspects that require further progress or investigation. ABS guidelines and other practice recommendations appear to impact the practice of brachytherapy.
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Braquiterapia/estadística & datos numéricos , Braquiterapia/normas , Adhesión a Directriz/estadística & datos numéricos , Pautas de la Práctica en Medicina/estadística & datos numéricos , Neoplasias de la Próstata/radioterapia , Encuestas de Atención de la Salud , Humanos , Masculino , Guías de Práctica Clínica como Asunto , Pautas de la Práctica en Medicina/normas , Neoplasias de la Próstata/epidemiología , Estados Unidos/epidemiologíaRESUMEN
PURPOSE: The purpose of this study was to evaluate the influence of potential contributing factors to the incidence of seed slippage and quality of prostate brachytherapy dosimetry comparing "coated" vs. "bare" seeds with a Mick applicator. METHODS AND MATERIALS: Two consecutive groups of 89 patients were treated with (125)I prostate brachytherapy at a high treatment volume single institution. All the patients were evaluated with Day 0 plain films of the pelvis and CT-based dosimetry analysis. The incidence of seed slippage was quantified. The seed slippage outcome was evaluated with respect to source type (bare vs. coated). The Day 0 prostate V(100), V(150), D90%, rectal V(100), and urethra D(30) outcomes were evaluated with respect to source type. RESULTS: A total of 13,512 seeds were placed in 178 patients. An average of 76 seeds and 16 needles were used for each patient. The bare seed group was significantly higher on fluoroscopy minutes (2.34 vs. 1.58 min), seed slippage (5 vs. 1.5 mm), volume of rectum receiving 100% of dose (0.05 vs. 0.0 cc), dose percentage received by 30% of urethra (119% vs. 113.64%), and volume of prostate receiving 100% of prescription dose (95.21% vs. 92.8%). No significant differences in volume of prostate receiving 150% of prescription dose, dose percentage received by 90% of prostate, vascular seed migration, or operating room procedure time were seen. No seed drift greater than 10mm outside the "packet" of other seeds was seen in the AnchorSeed (BrachySciences, a division of Biocompatibles, Inc. Oxford, CT) cohort. CONCLUSION: The report is the first to show the unique "fixity" of AnchorSeed to remain in position after deployment from the Mick applicator. Minimizing seed drag can reduce dose to the penile bulb, and maximize radiation coverage to the apex of the gland.
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Braquiterapia/instrumentación , Radioisótopos de Yodo/uso terapéutico , Neoplasias de la Próstata/radioterapia , Prótesis e Implantes , Humanos , Masculino , Movimiento (Física) , Radiofármacos/uso terapéutico , Resultado del TratamientoRESUMEN
BACKGROUND: Antibody Mediated Rejection (AMR) is a major cause of early graft loss, graft dysfunction, and chronic allograft nephropathy. Patients with elevated pre-transplant Panel Reactive Antibodies (PRA) are at much higher risk to develop AMR. We, retrospectively, studied the attack rate of AMR in sensitized recipients and evaluated whether preformed antibodies to donor Cross Reactive Epitope Group (CREG) and/or choice of induction immunosuppressive agent affected the frequency of this complication. METHODS: From the period between September 2002 and March 2008, we identified 19 sensitized renal transplant recipients (with mean PRA of 44.5+/-26%) and recorded the induction agent, number of HLA antigen mismatches, CREG match, CREG antibodies, PRA levels, clinical course, biopsy proven rejection episodes and presence of donor specific antibody. Nine patients were induced with Alemtuzumab (Campath-1H) and ten received horse or rabbit derived polyclonal antithymocyte antibody ATGAM (Pharmacia) or Thymoglobulin (Genzyme). All recipients were cross-match negative at time of transplant. RESULTS: Out of the 19 patients, 9 patients developed acute rejection (47.4%), 4 had AMR and 5 had Acute Cellular Rejection (ACR). Out of 19 patients, 9 patients had existing CREG antibodies (as per CREG Model proposed by McKenna, Takemoto et al.). All patients who developed AMR were found of have preformed antibodies to donor CREG. The median time interval for the development of acute humoral rejection was only 6 days and biopsies showed acute vascular rejection with Complement (C(4)D) deposition. CONCLUSIONS: Pre-existing CREG antibodies in sensitized renal transplant patients appear to identify a group at high risk to develop AMR.
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Anticuerpos Monoclonales/inmunología , Epítopos , Rechazo de Injerto/inmunología , Trasplante de Riñón/inmunología , Adulto , Negro o Afroamericano , Anciano , Reacciones Cruzadas , Femenino , Humanos , Terapia de Inmunosupresión , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Población Blanca , Adulto JovenRESUMEN
Human immunodeficiency virus (HIV)-1 patients who abuse opiates are at a greater risk of developing neurological complications of AIDS. Alterations in blood-brain barrier (BBB) integrity are associated with cytoskeletal disorganization and disruption of tight junction (TJ) integrity. We hypothesize that opiates in combination with HIV-1 viral proteins can modulate TJ expression in primary brain microvascular endothelial cells (BMVEC), thereby compromising BBB integrity and exacerbating HIV-1 neuropathogenesis. We investigated the effect of morphine and/or tat on the expression of TJ proteins ZO-1, JAM-2, Occludin and P-glycoprotein and the functional effects of TJ modulation in BMVEC. Morphine and/or tat, via the activation of pro-inflammatory cytokines, intracellular Ca(2+) release, and activation of myosin light chain kinase, modulated TJ expression resulting in decreased transendothelial electric resistance and enhanced transendothelial migration across the BBB. These studies may lead to the development of novel anti-HIV-1 therapeutics that target specific TJ proteins, thus preventing TJ disruption in opiate using HIV-1 patients.
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Complejo SIDA Demencia/virología , Síndrome de Inmunodeficiencia Adquirida/virología , Barrera Hematoencefálica/efectos de los fármacos , Permeabilidad Capilar/efectos de los fármacos , Morfina/farmacología , Uniones Estrechas/efectos de los fármacos , Productos del Gen tat del Virus de la Inmunodeficiencia Humana/farmacología , Complejo SIDA Demencia/sangre , Complejo SIDA Demencia/patología , Síndrome de Inmunodeficiencia Adquirida/sangre , Síndrome de Inmunodeficiencia Adquirida/inmunología , Síndrome de Inmunodeficiencia Adquirida/patología , Astrocitos/metabolismo , Astrocitos/patología , Astrocitos/virología , Barrera Hematoencefálica/metabolismo , Técnicas de Cultivo de Célula , Citocinas/metabolismo , Fura-2 , VIH-1/inmunología , VIH-1/patogenicidad , Humanos , Leucocitos Mononucleares/inmunología , Leucocitos Mononucleares/metabolismo , Leucocitos Mononucleares/patología , Leucocitos Mononucleares/virología , Morfina/sangre , Trastornos Relacionados con Sustancias , Uniones Estrechas/patología , Productos del Gen tat del Virus de la Inmunodeficiencia Humana/sangreAsunto(s)
Braquiterapia , Neoplasias de la Próstata/diagnóstico por imagen , Supervivencia sin Enfermedad , Relación Dosis-Respuesta en la Radiación , Humanos , Masculino , Variaciones Dependientes del Observador , Antígeno Prostático Específico/sangre , Neoplasias de la Próstata/sangre , Neoplasias de la Próstata/radioterapia , RadiografíaRESUMEN
PURPOSE: This Phase III study was performed to determine whether twice-daily (b.i.d.) radiotherapy (RT) resulted in better survival than once-daily (q.d.) RT for patients with limited-stage small-cell lung cancer (LD-SCLC). METHODS AND MATERIALS: A total of 310 patients with LD-SCLC initially received three cycles of etoposide and cisplatin. Subsequently, the 261 patients without significant progression were randomized to two cycles of etoposide and cisplatin plus either q.d. RT (50.4 Gy in 28 fractions) or split-course b.i.d. RT (24 Gy in 16 fractions, a 2.5-week break, and 24 Gy in 16 fractions) to the chest. Patients then received a sixth cycle of etoposide and cisplatin followed by prophylactic cranial RT. RESULTS: Follow-up ranged from 4.6 to 11.9 years (median, 7.4 years). The median survival and 5-year survival rate from randomization was 20.6 months and 21% for patients who received q.d. RT compared with 20.6 months and 22% for those who received b.i.d. RT (p = 0.68), respectively. No statistically significant differences were found in the rates of progression (p = 0.68), intrathoracic failure (p = 0.45), in-field failure (p = 0.62), or distant failure (p = 0.82) between the two treatment arms. No statistically significant difference was found in the overall rate of Grade 3 or worse (p = 0.83) or Grade 4 or worse toxicity (p = 0.95). Grade 3 or worse esophagitis (p = 0.05) was more common in the b.i.d. arm. Grade 5 toxicity occurred in 4 (3%) of 130 patients who received b.i.d. RT compared with 0 (0%) of 131 who received q.d. RT (p = 0.04). CONCLUSION: Although this study did not demonstrate an advantage to split-course b.i.d. RT, the long-term survival was favorable, likely reflecting the positive influences of concurrent combined modality therapy and prophylactic cranial RT.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma de Células Pequeñas/tratamiento farmacológico , Carcinoma de Células Pequeñas/radioterapia , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/radioterapia , Adulto , Anciano , Anciano de 80 o más Años , Cisplatino/administración & dosificación , Terapia Combinada , Irradiación Craneana , Fraccionamiento de la Dosis de Radiación , Etopósido/administración & dosificación , Femenino , Humanos , Masculino , Persona de Mediana Edad , Radioterapia/efectos adversos , Análisis de SupervivenciaRESUMEN
The aim of this study is to evaluate the target coverage, procedural techniques, and merits of Hybrid Interactive Mick (HIM) I125 transperineal permanent implantation (TPPI) of the prostate performed with 10 urologists in a community hospital. Detailed day 0 post-implant dosimetric evaluations of TPPI procedures were performed on 333 consecutive monotherapy patients treated between September 2000 and November 2003 at a single institution. All patients underwent TPPI with HIM. Pelvic and CXR films were obtained for a manual seed count at day 0 and again > day 90 on 175 patients. The HIM-prostate brachytherapy performed in a community hospital provided median D(90), V100, and V150 values of 157Gy, 94%, and 42.3%, respectively. 18% of patients had seed migration to the lungs while 2% had seed migration to the bladder. Only 7 patients (4%) had 2 or more seeds migrate to the lungs. Procedure times average 38 minutes and number of needles used averaged 18. The post-implant urinary retention rate was 2.1% Use of HIM-prostate brachytherapy in the community setting with multiple urologists reproducibly maintained excellent and consistent dosimetric coverage. Procedure times and number of needles used were minimized, and with careful attention to image-guided technique, seed migration to bladder and lung was also minimized.