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2.
BMJ Open ; 9(8): e026599, 2019 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-31401591

RESUMO

OBJECTIVES: To assess whether the Glasgow Admission Prediction Score (GAPS) is correlated with hospital length of stay, 6-month hospital readmission and 6-month all-cause mortality. This study represents a 6-month follow-up of patients who were included in an external validation of the GAPS' ability to predict admission at the point of triage. SETTING: Sampling was conducted between February and May 2016 at two separate emergency departments (EDs) in Sheffield and Glasgow. PARTICIPANTS: Data were collected prospectively at triage for consecutive adult patients who presented to the ED within sampling times. Any patients who avoided formal triage were excluded from the study. In total, 1420 patients were recruited. PRIMARY OUTCOMES: GAPS was calculated following triage and did not influence patient management. Length of hospital stay, hospital readmission and mortality against GAPS were modelled using survival analysis at 6 months. RESULTS: Of the 1420 patients recruited, 39.6% of these patients were initially admitted to hospital. At 6 months, 30.6% of patients had been readmitted and 5.6% of patients had died. For those admitted at first presentation, the chance of being discharged fell by 4.3% (95% CI 3.2% to 5.3%) per GAPS point increase. Cox regression indicated a 9.2% (95% CI 7.3% to 11.1%) increase in the chance of 6-month hospital readmission per point increase in GAPS. An association between GAPS and 6-month mortality was demonstrated, with a hazard increase of 9.0% (95% CI 6.9% to 11.2%) for every point increase in GAPS. CONCLUSION: A higher GAPS is associated with increased hospital length of stay, 6-month hospital readmission and 6-month all-cause mortality. While GAPS's primary application may be to predict admission and support clinical decision making, GAPS may provide valuable insight into inpatient resource allocation and bed planning.

4.
Nat Commun ; 10(1): 2720, 2019 06 20.
Artigo em Inglês | MEDLINE | ID: mdl-31221973

RESUMO

Public Health Laboratories (PHLs) in Puerto Rico did not escape the devastation caused by Hurricane Maria. We implemented a quality management system (QMS) approach to systematically reestablish laboratory testing, after evaluating structural and functional damage. PHLs were inoperable immediately after the storm. Our QMS-based approach began in October 2017, ended in May 2018, and resulted in the reestablishment of 92% of baseline laboratory testing capacity. Here, we share lessons learned from the historic recovery of the largest United States' jurisdiction to lose its PHL capacity, and provide broadly applicable tools for other jurisdictions to enhance preparedness for public health emergencies.

5.
J Clin Immunol ; 39(5): 494-504, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31172380

RESUMO

PURPOSE: Colitis is a common and serious complication of chronic granulomatous disorder (CGD) and requires assessment. Colonoscopy is invasive and carries risks of serious complication. We therefore assessed non-invasive monitoring via magnetic resonance imaging (MRI). We also evaluated fecal calprotectin (FCP), the Harvey-Bradshaw index (HBI) clinical score, and serum cytokines. METHODS: We recruited 10 patients with CGD (8 males, mean age 29.6 years), scored a modified HBI, and obtained stool for FCP. The following day we took blood for cytokine measurement via Luminex, performed MR enterography (scored by two independent radiologists using three systems: London score, CDMI, and MaRIA) followed by colonoscopy with disease activity measurement via ulcerative colitis endoscopic index of severity (UCEIS). We assessed patient experience after each investigation and overall preference with follow-up questionnaires. RESULTS: MRI scores correlated well with colonoscopic gold standard (for London score R2 0.91, p < 0.0001; for CDMI R2 0.83, p = 0.0006; for MaRIA R2 0.89, p = 0.0002). MRI was better tolerated and generally preferred, quicker, and visualized the entire large bowel whereas colonoscopy did not reach the terminal ileum in 3 participants. Elevated FCP accurately differentiated patients with colitis from those without, and log(calprotectin) correlated well with disease activity (R2 0.71, p = 0.009). Serum interleukin (IL)-12 concentration correlated with colitis activity but IL-1ß and TNF did not. Harvey-Bradshaw index did not correlate with colitis activity. CONCLUSIONS: MRI and fecal calprotectin are useful methods for monitoring CGD colitis and should reduce the need for colonoscopy in these patients. IL-12 may represent an appropriate target for treatment.

7.
Pediatr Emerg Care ; 2019 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-31136456

RESUMO

OBJECTIVE: The aim of the study was to compare emergency medical service resuscitation of pediatric and adult high-fidelity manikins in unstable supraventricular tachycardia. The primary objective was time to cardioversion. The secondary objective was to assess if the cardioversion was synchronized at the correct dosage for the manikin's weight. METHODS: Emergency medical service providers were voluntarily enrolled as part of an emergency medical service training program. Participants were randomized to either a pediatric or adult resuscitation as their study scenario. They then completed the second resuscitation as part of the training program. Participants completed presurvey and postsurvey. Resuscitations were videotaped and analyzed by a blinded reviewer. The study was powered to detect a 60-second difference in performance between pediatric and adult scenarios with a ß of 0.8 and 2-tailed α of 0.05 using an independent-samples t test. RESULTS: A total of 37 participants were enrolled. Participants in the pediatric arm had a longer mean time to cardioversion, but the difference was not statistically significant. The mean delay to cardioversion in the pediatric scenario was 34 seconds (197 vs 163 seconds; difference 95% confidence interval [CI], -5 to 73 seconds; P = 0.09). There was no significant difference in the percentage of participants who administered a correct dose (32% vs 50%; difference 95% CI, -50% to 13%; P = 0.75) or regarding synchronization of cardioversion (74% vs 83%; difference 95% CI, -36% to 17%; P = 0.42). CONCLUSIONS: Emergency medical service providers did not have a significant difference in time to cardioversion between pediatric and adult unstable supraventricular tachycardia simulations.

8.
Phys Rev Lett ; 122(18): 181101, 2019 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-31144890

RESUMO

The superradiant instability of rotating black holes with negative cosmological constant is studied by numerically solving the full (3+1)-dimensional Einstein equations. We find evidence for an epoch dominated by a solution with a single helical Killing vector and a multistage process with distinct superradiant instabilities.

9.
Rev Med Virol ; 29(4): e2049, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31016825

RESUMO

Patients with primary antibody deficiency syndromes such as X-linked agammaglobulinemia (XLA) and common variable immunodeficiency (CVID) are at increased risk of severe and invasive infection. Viral infection in these populations has been of increasing interest as evidence mounts that viruses contribute significant morbidity and mortality: this is mediated both directly and via aberrant immune responses. We explain the importance of the humoral immune system in defence against viral pathogens before highlighting several significant viral syndromes in patients with antibody deficiency. We explore historical cases of hepatitis C via contaminated immunoglobulin products, the predisposition to invasive enteroviral infections, prolonged excretion of vaccine-derived poliovirus, the morbidity of chronic norovirus infection, and recent literature revealing the importance of respiratory viral infections. We discuss evidence that herpesviruses may play a role in driving the inflammatory disease seen in a subset of patients. We explore the phenomenon of within-host evolution during chronic viral infection and the potential emergence of new pathogenic strains. We highlight novel and emerging viruses identified via deep sequencing techniques. We describe the treatment strategies that have been attempted in all these scenarios and the urgent outstanding questions for research.

10.
Sci Rep ; 9(1): 1605, 2019 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-30733557

RESUMO

Plasminogen activator inhibitor-1 (PAI-1) is a serine protease inhibitor (serpin) that regulates fibrinolysis, cell adhesion and cell motility via its interactions with plasminogen activators and vitronectin. PAI-1 has been shown to play a role in a number of diverse pathologies including cardiovascular diseases, obesity and cancer and is therefore an attractive therapeutic target. However the multiple patho-physiological roles of PAI-1, and understanding the relative contributions of these in any one disease setting, make the development of therapeutically relevant molecules challenging. Here we describe the identification and characterisation of fully human antibody MEDI-579, which binds with high affinity and specificity to the active form of human PAI-1. MEDI-579 specifically inhibits serine protease interactions with PAI-1 while conserving vitronectin binding. Crystallographic analysis reveals that this specificity is achieved through direct binding of MEDI-579 Fab to the reactive centre loop (RCL) of PAI-1 and at the same exosite used by both tissue and urokinase plasminogen activators (tPA and uPA). We propose that MEDI-579 acts by directly competing with proteases for RCL binding and as such is able to modulate the interaction of PAI-1 with tPA and uPA in a way not previously described for a human PAI-1 inhibitor.

11.
BMC Emerg Med ; 19(1): 9, 2019 01 17.
Artigo em Inglês | MEDLINE | ID: mdl-30654741

RESUMO

BACKGROUND: Decision-making concerning the limitation of potentially life-prolonging treatments is often challenging, particularly in the Emergency Department (ED). Current literature in this area of Emergency Medicine is limited and heterogeneous. We seek to determine the factors that influence ceiling of treatment institution in the ED. METHODS: We conducted a phenomenological qualitative study employing semi-structured interviews. Emergency Medicine Consultants were recruited via a sample of convenience from 5 hospitals in the West of Scotland. Data saturation was achieved after 15 interviews. Interviews were recorded, anonymised, transcribed, coded, and an iterative thematic analysis was carried out. RESULTS: A model was created to illustrate the identified themes. Patient wishes are central to decision-making. Acute clinical factors and patient-specific factors lay the foundations of ceiling of treatment decisions. This is heavily contextualised by family input, collateral information, anticipated outcome, and whether the patient is accepted for higher care. This decision-making process flows through a 'filter' of cultural and environmental factors. The overarching nature of patient benefit was found to be of key importance, framing all aspects of ceiling of treatment institution. Ultimately, all ceiling of treatment decisions result in one of three common patient pathways: full escalation, limited escalation, and maintenance of current care with the option of palliative care initiation. CONCLUSIONS: We present a conceptual model composed of 10 major thematic factors that influence Consultant ceiling of treatment decision-making in the ED. Clinicians should be cognizant of influential factors and associated biases when making these important and challenging decisions.


Assuntos
Tomada de Decisão Clínica , Serviço Hospitalar de Emergência , Assistência ao Paciente , Preferência do Paciente , Competência Clínica , Feminino , Humanos , Entrevistas como Assunto , Masculino , Pesquisa Qualitativa , Medição de Risco
12.
PLoS One ; 13(12): e0209516, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30589870

RESUMO

HIV-1 co-infection is a leading cause of susceptibility to tuberculosis (TB), with the risk of TB being increased at all stages of HIV-1 infection. Antiretroviral treatment (ART) is the most effective way to reduce the risk of TB in HIV-1 co-infected people. Studying protective, ART-induced, immune restoration in HIV-1 infected individuals sensitised by Mycobacterium tuberculosis (Mtb) can thus help identify mechanisms of protection against TB. In order to understand ART-mediated prevention of TB in HIV-1 infected adults, we investigated the expression of 30 genes in whole blood from HIV-1 infected patients during the first 6 months of ART-induced immune reconstitution. The 30 selected genes were previously described to be differentially expressed between sorted Mtb specific central and effector memory CD4 T cells. HIV-1 infected persons sensitised by Mtb were recruited in Khayelitsha, South Africa, when initiating ART. RNA was extracted from whole blood at initiation and 1, 3 and 6 months of ART. qRT-PCR was used to determine gene expression and three reference 'housekeeping' genes were used to calculate the fold change in the expression of each gene relative to day 0 of ART. Results were assessed longitudinally. We observed a decrease in the expression of a number of genes at 6 months of ART, reflecting a decrease in immune activation. However, following correction for multiple comparisons and increasing CD4 counts, only the decrease in CD27 gene expression remained statistically significant. While not statistically significant, a number of genes also showed increased expression at various timepoints, illustrating the broad regeneration of the T cell pool in HIV-1 infected adults on ART. Our findings generate hypotheses underlying ART- induced protective immune reconstitution and may pave the way for future studies to evaluate ART mediated prevention of TB in HIV-1 infected persons.


Assuntos
Coinfecção , Regulação da Expressão Gênica/efeitos dos fármacos , Infecções por HIV/tratamento farmacológico , Infecções por HIV/genética , Tuberculose/microbiologia , Terapia Antirretroviral de Alta Atividade , Contagem de Linfócito CD4 , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/metabolismo , Linfócitos T CD4-Positivos/virologia , Feminino , Perfilação da Expressão Gênica , Infecções por HIV/imunologia , Infecções por HIV/virologia , HIV-1/fisiologia , Humanos , Imunização , Testes de Liberação de Interferon-gama , Masculino , Mycobacterium tuberculosis/imunologia , Resultado do Tratamento , Tuberculose/imunologia , Tuberculose/metabolismo , Carga Viral
14.
J Med Biogr ; : 967772018754940, 2018 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-30165772

RESUMO

New Zealand-born surgeon Douglas Jolly was studying in London at the outbreak of the Spanish Civil War. He joined a British volunteer medical team and in December 1936 was placed in charge of a mobile medical unit of Spain's Republican Army. For the following two years, he took part in every major battle of the war, operating as close as possible to the front line. In that time he made significant contributions to trauma surgery, especially for abdominal injuries, and developed a 'three-points-forward' triage system. He described these medical innovations in a handbook which became highly influential among Allied medical services in Second World War, Korea and Vietnam. Jolly served with the Royal Army Medical Corps (RAMC) in the Middle East during Second World War and was awarded a military OBE.After the war, he became Chief Medical Officer of Queen Mary's Orthopaedic Hospital, Roehampton. He has been described as 'a pioneer in the field of surgical treatment for trauma and one of the most notable war surgeons of the 20th century.' In belated local recognition of this innovative and dedicated pioneer of trauma surgery, a memorial to Jolly will be unveiled in his home town of Cromwell, New Zealand in 2018.

15.
J Clin Monit Comput ; 2018 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-30264218

RESUMO

A cardiac arrest is a life-threatening event, often fatal. Whilst clinicians classify some of the cardiac arrests as potentially predictable, the majority are difficult to identify even in a post-incident analysis. Changes in some patients' physiology when analysed in detail can however be predictive of acute deterioration leading to cardiac or respiratory arrests. This paper seeks to exploit the causally-related changing patterns in signals such as heart rate, respiration rate, systolic blood pressure and peripheral cutaneous oxygen saturation to evaluate the predictability of cardiac arrests in critically ill paediatric patients in intensive care. In this paper we report the results of a framework constituting feature space embedding and time series forecasting methods to build an automated prediction system. The results were compared with clinical assessment of predictability. A sensitivity of 71% and specificity of 69% was obtained when the maximum value of Anomaly Index (12) in the 50 min (starting one hour and ending 10 min) before the arrest was considered for the case patients and a random 50 min of data was considered for the control set patients. A positive predictive value of 11% and negative predictive value of 98% was obtained with a prevalence of 5% by our method of prediction. While clinicians predicted 4 out of the 69 cardiac arrests (6%), the prediction system predicted 63 (91%) cardiac arrests. Prospective validation of the automated system remains.

16.
Infect Immun ; 86(11)2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30104213

RESUMO

Listeria monocytogenes is a foodborne pathogen that infects the placenta and can cause pregnancy complications. Listeriosis usually occurs as a sporadic infection, but large outbreaks are also reported. Virulence from clinical isolates is rarely analyzed due to the large number of animals required, but this knowledge could help guide the response to an outbreak. We implemented a DNA barcode system using signature tags that allowed us to efficiently assay variations in virulence across a large number of isolates. We tested 77 signature-tagged clones of clinical L. monocytogenes strains from 72 infected human placentas and 5 immunocompromised patients, all of which were isolated since 2000. These strains were tested for virulence in a modified competition assay in comparison to that of the laboratory strain 10403S. We used two in vivo models of listeriosis: the nonpregnant mouse and the pregnant guinea pig. Strains that were frequently found at a high abundance within infected organs were considered hypervirulent, while strains frequently found at a low abundance were considered hypovirulent. Virulence split relatively evenly among hypovirulent strains, hypervirulent strains, and strains as virulent as 10403S. The laboratory strain was found to have an intermediate virulence phenotype, supporting its suitability for use in pathogenesis studies. Further, we found that splenic virulence and placental virulence are closely linked in both the guinea pig and mouse models. This suggests that outbreak and sporadic pregnancy-associated L. monocytogenes strains are not generally more virulent than lab reference strains. However, some strains did show consistent and reproducible virulence differences, suggesting that their further study may reveal deeper insights into the biological underpinnings of listeriosis.

17.
J Infect Dis ; 2018 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-30137432

RESUMO

Background: Persistent hepatitis E virus (HEV) infection is described in a number of immunosuppressive conditions. We aimed to determine the risk of persistent HEV infection in patients with primary or secondary antibody deficiency. Methods: Two hundred and forty five antibody deficient patients on regular immunoglobulin replacement were tested for HEV RNA and anti-HEV IgG. Immunoglobulin products and plasma from nine antibody-deficient patients pre- and post-IVIG, five recently treated patients with persistent HEV infection and five healthy patients recovered from acute HEV infection were analysed for anti-HEV IgG and for antibody reacting with HEV antigen (HEV-Ag). Results: No antibody deficient patient had detectable plasma HEV RNA. Anti-HEV IgG was detected in 38.8% of patients. All ten immunoglobulin products tested contained anti-HEV capable of neutralising HEV-Ag. Plasma samples following IVIG infusion demonstrated higher anti-HEV IgG and neutralising activity compared with pre-IVIG samples. Neutralising activity was similar to healthy patients with recent acute HEV infection. Conclusion: The risk of persistent HEV infection in patients with antibody deficiency appears extremely low. This may be due to passive seroprotection afforded by the ubiquitous presence of anti-HEV in immunoglobulin replacement products.

18.
Ann Intern Med ; 168(12): 901-902, 2018 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-29913502
19.
Front Immunol ; 9: 903, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29755473

RESUMO

Neutrophils exert both positive and negative influences on the host response to tuberculosis, but the mechanisms by which these differential effects are mediated are unknown. We studied the impact of live and dead neutrophils on the control of Mycobacterium tuberculosis using a whole blood bioluminescence-based assay, and assayed supernatant cytokine concentrations using Luminex™ technology and ELISA. CD15+ granulocyte depletion from blood prior to infection with M. tuberculosis-lux impaired control of mycobacteria by 96 h, with a greater effect than depletion of CD4+, CD8+, or CD14+ cells (p < 0.001). Augmentation of blood with viable granulocytes significantly improved control of mycobacteria by 96 h (p = 0.001), but augmentation with necrotic granulocytes had the opposite effect (p = 0.01). Both augmentations decreased supernatant concentrations of tumor necrosis factor and interleukin (IL)-12 p40/p70, but necrotic granulocyte augmentation also increased concentrations of IL-10, G-CSF, GM-CSF, and CCL2. Necrotic neutrophil augmentation reduced phagocytosis of FITC-labeled M. bovis BCG by all phagocytes, whereas viable neutrophil augmentation specifically reduced early uptake by CD14+ cells. The immunosuppressive effect of dead neutrophils required necrotic debris rather than supernatant. We conclude that viable neutrophils enhance control of M. tuberculosis in blood, but necrotic neutrophils have the opposite effect-the latter associated with induction of IL-10, growth factors, and chemoattractants. Our findings suggest a mechanism by which necrotic neutrophils may exert detrimental effects on the host response in active tuberculosis.

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