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1.
Transfusion ; 64 Suppl 2: S85-S92, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38351716

RESUMEN

INTRODUCTION: The use of low titer O whole blood (LTOWB) has expanded although it remains unclear how many civilian trauma centers are using LTOWB. METHODS: We analyzed data on civilian LTOWB recipients in the American College of Surgeons Trauma Quality Improvement Program (TQIP) database 2020-2021. Unique facility keys were used to determine the number of centers that used LTOWB in that period. RESULTS: A total of 16,603 patients received LTOWB in the TQIP database between 2020 and 2021; 6600 in 2020, and 10,003 in 2021. The total number of facilities that reported LTOWB use went from 287/779 (37%) in 2020 to 302/795 (38%) in 2021. Between 2020 and 2021, among all level 1-3 designated trauma facilities that report to TQIP LTOWB use increased at level-1 centers (118 to 129), and level-2 centers (81 to 86), but decreased in level-3 facilities (9 to 4). Among pediatric and dual pediatric-adult designated hospitals there was a decrease in the number of pediatric level-1 centers (29 to 28) capable of administering LTOWB. Among centers with either single or dual level-1 trauma center designation with adult centers, the number that administered LTOWB to injured pediatric patients also decreased from 17 to 10, respectively. CONCLUSIONS: There was an increase in the number of facilities transfusing LTOWB between 2020 and 2021. The use of LTOWB is underutilized in children at centers that have it available. These findings inform the expansion of LTOWB use in trauma.


Asunto(s)
Mejoramiento de la Calidad , Sistema de Registros , Centros Traumatológicos , Heridas y Lesiones , Humanos , Heridas y Lesiones/terapia , Heridas y Lesiones/sangre , Masculino , Sistema del Grupo Sanguíneo ABO , Transfusión Sanguínea/estadística & datos numéricos , Femenino , Encuestas y Cuestionarios , Adulto
2.
Am J Respir Crit Care Med ; 208(8): 868-878, 2023 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-37556679

RESUMEN

Rationale: Pneumococcal pneumonia remains a global health problem. Pneumococcal colonization increases local and systemic protective immunity, suggesting that nasal administration of live attenuated Streptococcus pneumoniae (Spn) strains could help prevent infections. Objectives: We used a controlled human infection model to investigate whether nasopharyngeal colonization with attenuated S. pneumoniae strains protected against recolonization with wild-type (WT) Spn (SpnWT). Methods: Healthy adults aged 18-50 years were randomized (1:1:1:1) for nasal administration twice (at a 2-wk interval) with saline solution, WT Spn6B (BHN418), or one of two genetically modified Spn6B strains, SpnA1 (Δfhs/piaA) or SpnA3 (ΔproABC/piaA) (Stage I). After 6 months, participants were challenged with SpnWT to assess protection against the homologous serotype (Stage II). Measurements and Main Results: 125 participants completed both study stages per intention to treat. No serious adverse events were reported. In Stage I, colonization rates were similar among groups: SpnWT, 58.1% (18 of 31); SpnA1, 60% (18 of 30); and SpnA3, 59.4% (19 of 32). Anti-Spn nasal IgG levels after colonization were similar in all groups, whereas serum IgG responses were higher in the SpnWT and SpnA1 groups than in the SpnA3 group. In colonized individuals, increases in IgG responses were identified against 197 Spn protein antigens and serotype 6 capsular polysaccharide using a pangenome array. Participants given SpnWT or SpnA1 in Stage I were partially protected against homologous challenge with SpnWT (29% and 30% recolonization rates, respectively) at stage II, whereas those exposed to SpnA3 achieved a recolonization rate similar to that in the control group (50% vs. 47%, respectively). Conclusions: Nasal colonization with genetically modified live attenuated Spn was safe and induced protection against recolonization, suggesting that nasal administration of live attenuated Spn could be an effective strategy for preventing pneumococcal infections. Clinical trial registered with the ISRCTN registry (ISRCTN22467293).


Asunto(s)
Infecciones Neumocócicas , Streptococcus pneumoniae , Adulto , Humanos , Virulencia , Nariz , Infecciones Neumocócicas/prevención & control , Inmunización , Anticuerpos Antibacterianos , Inmunoglobulina G , Vacunas Neumococicas/uso terapéutico
3.
Am J Respir Crit Care Med ; 206(11): 1379-1392, 2022 12 01.
Artículo en Inglés | MEDLINE | ID: mdl-35802840

RESUMEN

Rationale: Streptococcus pneumoniae serotype 3 (SPN3) is a cause of invasive pneumococcal disease and associated with low carriage rates. Following the introduction of pediatric 13-valent pneumococcal conjugate vaccine (PCV13) programs, SPN3 declines are less than other vaccine serotypes and incidence has increased in some populations coincident with a shift in predominant circulating SPN3 clade, from I to II. A human challenge model provides an effective means for assessing the impact of PCV13 on SPN3 in the upper airway. Objectives: To establish SPN3's ability to colonize the nasopharynx using different inoculum clades and doses, and the safety of an SPN3 challenge model. Methods: In a human challenge study involving three well-characterized and antibiotic-sensitive SPN3 isolates (PFESP306 [clade Ia], PFESP231 [no clade], and PFESP505 [clade II]), inoculum doses (10,000, 20,000, 80,000, and 160,000 cfu/100 µl) were escalated until maximal colonization rates were achieved, with concurrent acceptable safety. Measurement and Main Results: Presence and density of experimental SPN3 nasopharyngeal colonization in nasal wash samples, assessed using microbiological culture and molecular methods, on Days 2, 7, and 14 postinoculation. A total of 96 healthy participants (median age 21, interquartile range 19-25) were inoculated (n = 6-10 per dose group, 10 groups). Colonization rates ranged from 30.0-70.0% varying with dose and isolate. 30.0% (29/96) reported mild symptoms (82.8% [24/29] developed a sore throat); one developed otitis media requiring antibiotics. No serious adverse events occurred. Conclusions: An SPN3 human challenge model is feasible and safe with comparable carriage rates to an established Serotype 6B human challenge model. SPN3 carriage may cause mild upper respiratory symptoms.


Asunto(s)
Infecciones Neumocócicas , Streptococcus pneumoniae , Humanos , Niño , Lactante , Adulto Joven , Adulto , Serogrupo , Portador Sano , Vacunas Neumococicas/uso terapéutico , Infecciones Neumocócicas/prevención & control , Nasofaringe/microbiología , Antibacterianos/uso terapéutico , Antibacterianos/farmacología
4.
Am J Emerg Med ; 63: 181.e1-181.e3, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-36270959

RESUMEN

In patients with biliary or pancreatic disease, endoscopic retrograde cholangiopancreatography (ERCP) is a common and important therapeutic and diagnostic procedure. Stent migration is a possible complication occurring in approximately 5-10% of cases. This case presents a 47-year-old male with chest pain and found to have biliary stent migration to the pericardial sac causing septic pericarditis and cardiac tamponade. Highlighting this devastating complication, this case demonstrates an opportunity for emergency physicians (EP) to diagnose and monitor patients for post-operative and post-procedural complications. In the emergency department, EPs are well positioned to use ultrasound as a diagnostic and monitoring tool for cardiac tamponade.


Asunto(s)
Taponamiento Cardíaco , Humanos , Persona de Mediana Edad , Taponamiento Cardíaco/diagnóstico por imagen , Taponamiento Cardíaco/etiología , Taponamiento Cardíaco/cirugía
5.
Community Ment Health J ; 59(4): 680-691, 2023 05.
Artículo en Inglés | MEDLINE | ID: mdl-36374379

RESUMEN

Suicide is a global concern with rates in Australia continuing to increase. Effective post-suicidal care is critical for reducing persistent suicidal behaviour. One model of care is that adopted by Alfred Health, delivering a multidisciplinary, hybrid clinical and non-clinical (psycho-social support), assertive outreach approach. This study measured improvements in resilience and wellbeing, changes to distress and suicidal ideation at least 6-months post-discharge from care. Thirty-one consumers participated including a one-on-one interview to gather qualitative feedback. There was a significant change on all outcome measures with large effect sizes. Participants had significantly reduced suicidal ideation and distress and increased coping self-efficacy, hope and well-being. The qualitative findings indicated that a key component to recovery was the staff. Limitations included a low sample size, and broad time range of follow-up data collection. Providing assertive, multidisciplinary, collaborative and outreach-focused post-suicidal care can increase and sustain protective psychological factors and reduced suicidal ideation in most individuals.


Asunto(s)
Cuidados Posteriores , Ideación Suicida , Humanos , Estudios Longitudinales , Factores de Riesgo , Alta del Paciente
6.
J Infect Dis ; 225(9): 1626-1631, 2022 05 04.
Artículo en Inglés | MEDLINE | ID: mdl-34159375

RESUMEN

Pneumococcal conjugate vaccine (PCV) efficacy is lower for noninvasive pneumonia than invasive disease. In this study, participants were immunized with 13-valent PCV (PCV13) or hepatitis A vaccine (control). Bronchoalveolar lavage samples were taken between 2 and 6 months and serum at 4 and 7 weeks postvaccination. In the lung, anti-capsular immunoglobulin G (IgG) levels were higher in the PCV13 group compared to controls for all serotypes, except 3 and 6B. Systemically, IgG levels were elevated in the PCV13 group at 4 weeks for all serotypes, except serotype 3. IgG in bronchoalveolar lavage and serum positively correlated for nearly all serotypes. PCV13 shows poor immunogenicity to serotype 3, implying lack of protective efficacy. Clinical Trials Registration. ISRCTN 45340436.


Asunto(s)
Infecciones Neumocócicas , Anticuerpos Antibacterianos , Humanos , Inmunoglobulina G , Lactante , Pulmón , Vacunas Neumococicas , Serogrupo , Vacunas Conjugadas
7.
Prehosp Emerg Care ; 26(sup1): 80-87, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35001825

RESUMEN

Noninvasive ventilation (NIV), including bilevel positive airway pressure and continuous positive airway pressure, is a safe and important therapeutic option in the management of prehospital respiratory distress. NAEMSP recommends:NIV should be used in the management of prehospital patients with respiratory failure, such as those with chronic obstructive pulmonary disease, asthma, and pulmonary edema.NIV is a safe intervention for use by Emergency Medical Technicians.Medical directors must assure adequate training in NIV, including appropriate patient selection, NIV system operation, administration of adjunctive medications, and assessment of clinical response.Medical directors must implement quality assessment and improvement programs to assure optimal application of and outcomes from NIV.Novel NIV methods such as high-flow nasal cannula and helmet ventilation may have a role in prehospital care.


Asunto(s)
Servicios Médicos de Urgencia , Ventilación no Invasiva , Insuficiencia Respiratoria , Presión de las Vías Aéreas Positiva Contínua , Humanos , Respiración Artificial , Insuficiencia Respiratoria/terapia
8.
Prehosp Emerg Care ; 26(4): 566-572, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-34313543

RESUMEN

Objective: EMS use of lights and sirens has long been employed in EMS systems, despite an increased risk of motor vehicle collisions associated with their use. The specific aims of this study were to assess the current use of lights and sirens during the transport of trauma patients in a busy metropolitan area and to subsequently develop a novel tool, the Critical Intervention Screen, to aid EMS professionals tasked with making transport decisions in the presence of acute injury.Methods: This single-center, retrospective study included all patients transported to an academic Level One trauma center by ground ambulance from the scene of presumed or known injury. A subset of patients was identified as being most likely to benefit from shorter transport times if they received one of the following critical interventions within 20 minutes of emergency department arrival: intubation, thoracotomy, chest tube, blood products, central line, arterial line, REBOA, disposition to an operating room, or death. Stepwise logistic regression was employed for the development of the Critical Intervention Screen, with a subset of data retained for internal validation.Results: 1296 patients were available for analysis. Overall, 217 patients (16.7%) received a critical intervention, and 112 patients (8.6%) of those patients received a critical intervention within 20 minutes of emergency department arrival. At baseline, EMS use of lights and sirens was 91.1% sensitive and 80.3% specific for receiving a critical intervention. Stepwise logistic regression demonstrated that the need for assisted ventilation, GCS Motor < 6, and penetrating trauma to the trunk were the most predictive prehospital data for receiving at least one critical intervention. The Critical Intervention Screen, defined as having at least one of these risk factors in the prehospital setting, modestly increased sensitivity and specificity (96.4% and 87.9%, respectively) predicting the need for a critical intervention.Conclusion: These findings indicate that EMS are able to correctly identify high-acuity trauma patients, but at times employ L&S during the transport of patients with a low likelihood of receiving a time-sensitive intervention upon emergency department arrival. Therefore, the Critical Intervention Screen has the potential to reduce the use of lights and sirens and improve EMS safety.


Asunto(s)
Servicios Médicos de Urgencia , Accidentes de Tránsito , Servicio de Urgencia en Hospital , Humanos , Estudios Retrospectivos , Centros Traumatológicos
9.
Am J Respir Crit Care Med ; 203(5): 604-613, 2021 03 01.
Artículo en Inglés | MEDLINE | ID: mdl-32941735

RESUMEN

Rationale: Pneumococcal colonization is key to the pathogenesis of invasive disease but is also immunogenic in young adults, protecting against recolonization. Colonization is rarely detected in older adults, despite high rates of pneumococcal disease.Objectives: To establish experimental human pneumococcal colonization in healthy adults aged 50-84 years, to measure the immune response to pneumococcal challenge, and to assess the protective effect of prior colonization against autologous strain rechallenge.Methods: Sixty-four participants were inoculated with Streptococcus pneumoniae (serotype 6B; 80,000 cfu in each nostril). Colonization was determined by bacterial culture of nasal wash, and humoral immune responses were assessed by anticapsular and antiprotein IgG concentrations.Measurements and Main Results: Experimental colonization was established in 39% of participants (25/64) with no adverse events. Colonization occurred in 47% (9/19) of participants aged 50-59 compared with 21% (3/14) in those aged ≥70 years. Previous pneumococcal polysaccharide vaccination did not protect against colonization. Colonization did not confer serotype-specific immune boosting, with a geometric mean titer (95% confidence interval) of 2.7 µg/ml (1.9-3.8) before the challenge versus 3.0 (1.9-4.7) 4 weeks after colonization (P = 0.53). Furthermore, pneumococcal challenge without colonization led to a drop in specific antibody concentrations from 2.8 µg/ml (2.0-3.9) to 2.2 µg/ml (1.6-3.0) after the challenge (P = 0.006). Antiprotein antibody concentrations increased after successful colonization. Rechallenge with the same strain after a median of 8.5 months (interquartile range, 6.7-10.1) led to recolonization in 5/16 (31%).Conclusions: In older adults, experimental pneumococcal colonization is feasible and safe but demonstrates different immunological outcomes compared with younger adults in previous studies.


Asunto(s)
Anticuerpos Antibacterianos/inmunología , Portador Sano/inmunología , Infecciones Neumocócicas/inmunología , Streptococcus pneumoniae/inmunología , Factores de Edad , Anciano , Anciano de 80 o más Años , Infecciones Asintomáticas , Técnicas de Cultivo , Estudios de Factibilidad , Femenino , Humanos , Inmunidad Humoral/inmunología , Inmunoglobulina G/inmunología , Masculino , Persona de Mediana Edad , Cavidad Nasal , Líquido del Lavado Nasal , Infecciones Neumocócicas/prevención & control , Vacunas Neumococicas/uso terapéutico
10.
Wilderness Environ Med ; 33(2): 224-231, 2022 06.
Artículo en Inglés | MEDLINE | ID: mdl-35459612

RESUMEN

Wilderness medicine and telemedicine seemingly exist at opposite ends of the clinical continuum. However, these 2 specialties share a common history and the literature abounds with examples of successful deployment of telemedicine to resource limited settings. The recent widespread adoption of telemedicine has important ramifications for wilderness providers. Telemedicine is inherently reliant on some sort of technology. There is a wide spectrum of complexity involved, but in general these systems rely on a hardware component, a software component, and a network system to transmit information from place to place. Today, connectivity is nearly ubiquitous through access to cellular networks, Wi-Fi, or communication satellites. However, bandwidth, defined as the amount of data which can be transmitted through a given connection over time, remains a limiting factor for many austere settings. Telemedicine services are typically organized into 4 categories: 1) live/interactive; 2) store and forward; 3) remote patient monitoring; and 4) mHealth. Each of these categories has an applicable wilderness medicine use case which will be reviewed in this paper. Though the regulatory environment remains complex, there is enormous potential for telemedicine to enhance the practice of wilderness medicine. Drones are likely to transform wilderness medicine supply chains by facilitating delivery of food, shelter, and medicines and are able to enhance search and rescue efforts. Remote consultations can be paired with remote patient monitoring technology to deliver highly specialized care to austere environments. Early feasibility studies are promising, but further prospective data will be required to define future best practices for wilderness telemedicine.


Asunto(s)
Telemedicina , Medicina Silvestre , Humanos
11.
Am J Respir Crit Care Med ; 201(3): 335-347, 2020 02 01.
Artículo en Inglés | MEDLINE | ID: mdl-31626559

RESUMEN

Rationale: Pneumococcal pneumonia remains a global health problem. Colonization of the nasopharynx with Streptococcus pneumoniae (Spn), although a prerequisite of infection, is the main source of exposure and immunological boosting in children and adults. However, our knowledge of how nasal colonization impacts on the lung cells, especially on the predominant alveolar macrophage (AM) population, is limited.Objectives: Using a controlled human infection model to achieve nasal colonization with 6B serotype, we investigated the effect of Spn colonization on lung cells.Methods: We collected BAL from healthy pneumococcal-challenged participants aged 18-49 years. Confocal microscopy and molecular and classical microbiology were used to investigate microaspiration and pneumococcal presence in the lower airways. AM opsonophagocytic capacity was assessed by functional assays in vitro, whereas flow cytometry and transcriptomic analysis were used to assess further changes on the lung cellular populations.Measurements and Main Results: AMs from Spn-colonized individuals exhibited increased opsonophagocytosis to pneumococcus (11.4% median increase) for approximately 3 months after experimental pneumococcal colonization. AMs also had increased responses against other bacterial pathogens. Pneumococcal DNA detected in the BAL samples of Spn-colonized individuals were positively correlated with nasal pneumococcal density (r = 0.71; P = 0.029). Similarly, AM-heightened opsonophagocytic capacity was correlated with nasopharyngeal pneumococcal density (r = 0.61, P = 0.025).Conclusions: Our findings demonstrate that nasal colonization with pneumococcus and microaspiration prime AMs, leading to brisker responsiveness to both pneumococcus and unrelated bacterial pathogens. The relative abundance of AMs in the alveolar spaces, alongside their potential for nonspecific protection, render them an attractive target for novel vaccines.


Asunto(s)
Macrófagos Alveolares/inmunología , Nasofaringe/microbiología , Nariz/microbiología , Streptococcus pneumoniae/aislamiento & purificación , Adolescente , Adulto , Bacterias/inmunología , Humanos , Persona de Mediana Edad , Aspiración Respiratoria , Adulto Joven
12.
Technol Forecast Soc Change ; 165: 120531, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-36536773

RESUMEN

Covid-19, a corona virus, has maintained its momentum in spreading among communities. In this context of social crisis, this study seeks to identify the reasons for the partial failure to fulfill the intended goal of lockdown, and to formulate an inclusive behavioral model reflecting comprehensive human behavior and social psychology. In order to answer the research questions, this study has conducted extensive interviews among individuals who were targets of the lockdown system. From this exploratory and qualitative investigation, researchers have recognized four paradigms as the key to understanding human behavior and social psychology in violating lockdown as a social isolation system during this period of crisis. The identified parameters depicting social behavior are: Derogation and Argument (SDA), Tangible Need and Deficiency (TND), Intangible Desire and Expectancy (IDE), and Evaluation of Benefit and Loss (UBL). Finally, as a comprehensive guideline, a grounded theory of the social behavior 'paradigm for lockdown violation (PLV)' is explored as the reason for the violation of the social system.

13.
Emerg Infect Dis ; 26(11): 2770-2771, 2020 11.
Artículo en Inglés | MEDLINE | ID: mdl-32917294

RESUMEN

PCR of upper respiratory specimens is the diagnostic standard for severe acute respiratory syndrome coronavirus 2 infection. However, saliva sampling is an easy alternative to nasal and throat swabbing. We found similar viral loads in saliva samples and in nasal and throat swab samples from 110 patients with coronavirus disease.


Asunto(s)
Betacoronavirus/aislamiento & purificación , Técnicas de Laboratorio Clínico/métodos , Infecciones por Coronavirus/diagnóstico , Neumonía Viral/diagnóstico , Saliva/virología , Adulto , Anciano , COVID-19 , Prueba de COVID-19 , Femenino , Humanos , Masculino , Persona de Mediana Edad , Nariz/virología , Pandemias , Faringe/virología , SARS-CoV-2 , Carga Viral
14.
J Infect Dis ; 219(12): 1989-1993, 2019 05 24.
Artículo en Inglés | MEDLINE | ID: mdl-30690468

RESUMEN

Pneumococcal colonization is rarely studied in adults, except as part of family surveys. We report the outcomes of colonization screening in healthy adults (all were nonsmokers without major comorbidities or contact with children aged <5 years) who had volunteered to take part in clinical research. Using nasal wash culture, we detected colonization in 6.5% of volunteers (52 of 795). Serotype 3 was the commonest serotype (10 of 52 isolates). The majority of the remaining serotypes (35 of 52 isolates) were nonvaccine serotypes, but we also identified persistent circulation of serotypes 19A and 19F. Resistance to at least 1 of 6 antibiotics tested was found in 8 of 52 isolates.


Asunto(s)
Infecciones Neumocócicas/inmunología , Vacunas Neumococicas/inmunología , Streptococcus pneumoniae/inmunología , Vacunas Conjugadas/inmunología , Adulto , Antibacterianos/inmunología , Farmacorresistencia Bacteriana/inmunología , Femenino , Voluntarios Sanos , Humanos , Masculino , Serogrupo , Reino Unido , Adulto Joven
15.
Can J Psychiatry ; 63(10): 683-691, 2018 10.
Artículo en Inglés | MEDLINE | ID: mdl-29706116

RESUMEN

OBJECTIVE: To examine psychotropic medication prescription practices in federal Canadian penitentiaries. METHOD: 468 files were drawn from a purposive sample of thirteen Canadian federal institutions representing the five regions, different security levels, and male and female designated facilities. Information on the names of all psychotropic medications prescribed, indications for use, dosage, frequency, and route of administration was retrieved. Designation of approved or off-label use of medications was determined by consulting: (1) the Health Canada (2016) Drug Product Database, (2) the Canadian Compendium of Pharmaceuticals and Specialties 2016, and (3) the American Hospital Formulary Service Drug Information 2016. Prescription rates were examined by gender, Indigenous ancestry, drug class, institutional infractions, and current offence. RESULTS: 36.2% of prescriptions for psychotropic medication were coded as 'off-label'. Anxiolytic/hypnotics drugs were the psychotropic drugs most commonly used for off-label purposes. There were no differences in the prevalence of approved versus off-label prescriptions based on Indigenous ancestry or gender, and no pattern of elevated off-label prescription practices for offenders involved in institutional misconducts or those sentenced for the most serious crimes. CONCLUSIONS: The rates of prescribing 'off-label' psychotropic medication are not elevated relative to other correctional settings or to rates cited in Canadian surveys conducted in the community.


Asunto(s)
Prescripciones de Medicamentos/estadística & datos numéricos , Trastornos Mentales/tratamiento farmacológico , Uso Fuera de lo Indicado/estadística & datos numéricos , Prisioneros/estadística & datos numéricos , Prisiones/estadística & datos numéricos , Psicotrópicos/uso terapéutico , Adulto , Canadá , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto Joven
17.
Am J Respir Crit Care Med ; 194(12): 1523-1531, 2016 12 15.
Artículo en Inglés | MEDLINE | ID: mdl-27403678

RESUMEN

RATIONALE: We have previously demonstrated that experimental pneumococcal carriage enhances immunity and protects healthy adults against carriage reacquisition after rechallenge with a homologous strain. OBJECTIVES: To investigate the role of naturally acquired pneumococcal protein and polysaccharide (PS)-specific immunity in protection against carriage acquisition using a heterologous challenge model. METHODS: We identified healthy volunteers that were naturally colonized with pneumococcus and, after clearance of their natural carriage episode, challenged them with a heterologous 6B strain. In another cohort of volunteers we assessed 6BPS-specific, PspA-specific, and PspC-specific IgG and IgA plasma and memory B-cell populations before and 7, 14, and 35 days after experimental pneumococcal inoculation. MEASUREMENTS AND MAIN RESULTS: Heterologous challenge with 6B resulted in 50% carriage among volunteers with previous natural pneumococcal carriage. Protection from carriage was associated with a high number of circulating 6BPS IgG-secreting memory B cells at baseline. There were no associations between protection from carriage and baseline levels of 6BPS IgG in serum or nasal wash, PspA-specific, or PspC-specific memory B cells or plasma cells. In volunteers who did not develop carriage, the number of circulating 6BPS memory B cells decreased and the number of 6BPS plasma cells increased postinoculation. CONCLUSIONS: Our data indicate that naturally acquired PS-specific memory B cells, but not levels of circulating IgG at time of pneumococcal exposure, are associated with protection against carriage acquisition.


Asunto(s)
Anticuerpos Antibacterianos/inmunología , Linfocitos B/inmunología , Portador Sano/inmunología , Infecciones Neumocócicas/prevención & control , Streptococcus pneumoniae/inmunología , Adolescente , Adulto , Femenino , Humanos , Persona de Mediana Edad , Nasofaringe/inmunología , Polisacáridos/inmunología , Adulto Joven
18.
BMC Pulm Med ; 17(1): 83, 2017 May 05.
Artículo en Inglés | MEDLINE | ID: mdl-28476111

RESUMEN

BACKGROUND: Broncho alveolar lavage (BAL) is widely used for investigative research to study innate, cellular and humoral immune responses, and in early phase drug trials. Conventional (multiple use) flexible bronchoscopes have time and monetary costs associated with cleaning, and carries a small risk of cross infection. Single use bronchoscopes may provide an alternative, but have not been evaluated in this context. METHODS: Healthy volunteers underwent bronchoscopy at a day-case clinical research unit using the Ambu® aScopeTM single-use flexible intubation bronchoscope. Broncho alveolar lavage was performed from a sub segmental bronchus within the right middle lobe; a total of 200 ml of warmed normal saline was instilled then aspirated using handheld suction. BAL volume yield, cell yield and viability were recorded. RESULTS: Ten volunteers, (mean age 23 years, six male) participated. Bronchoscopies were carried out by one of two senior bronchoscopists, experienced in the technique of obtaining BAL for research purposes. The results were compared to 50 (mean age 23, 14 male) procedures performed using the conventional scope by the same two bronchoscopists. The total volume yield was significantly higher in the disposable group median 152 ml (IQR 141-166 ml) as compared to conventional 124 ml (110-135 ml), p = <0.01. The total cell yield and viability were similar in both groups, with no significant differences. CONCLUSIONS: With single use bronchoscopes, we achieved a larger BAL volume yield than conventional bronchoscopes, with comparable cell yield and viability. Better volume yields can potentially reduce post procedure side effects such as pleuritic chest pain and cough. The risk of cross infection can be eliminated, providing reassurance to researchers and participants. Reduced maintenance requirements can be cost effective. These could potentially be used for early phase drug development studies. TRIAL REGISTRATION: This trial was registered prospectively in July 2015 with the National Clinical Trials register, with the following registration number assigned: NCT 02515591 .


Asunto(s)
Investigación Biomédica/instrumentación , Lavado Broncoalveolar/instrumentación , Broncoscopios , Adulto , Líquido del Lavado Bronquioalveolar/citología , Supervivencia Celular , Infección Hospitalaria/prevención & control , Equipos Desechables , Equipo Médico Durable , Femenino , Voluntarios Sanos , Humanos , Masculino , Estudios Prospectivos , Adulto Joven
19.
J Infect Dis ; 213(11): 1809-19, 2016 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-26810369

RESUMEN

BACKGROUND: Oral vaccination with live-attenuated Salmonella Typhi strain Ty21a is modestly efficacious, but the mechanisms of protection are currently unknown. While humoral and cellular immune responses are well described in peripheral blood, the cellular response at the intestinal mucosa has never been directly assessed. METHODS: We vaccinated healthy adults with Ty21a and assessed humoral and cellular immunity in vaccinated volunteers and controls after 18 days. Immunoglobulin levels were assessed in peripheral blood by an enzyme-linked immunosorbent assay. Cellular responses were assessed in peripheral blood and at the duodenal and colonic mucosa by flow cytometry. RESULTS: We demonstrate the generation of Ty21a-responsive and heterologous influenza virus-responsive CD4(+) and CD8(+) T cells at the duodenal mucosa. All duodenal responses were consistently correlated, and no responses were observed at the colonic mucosa. Peripheral anti-lipopolysaccharide immunoglobulin G and immunoglobulin A responses were significantly correlated with duodenal responses. The assessment of integrin ß7 expression intensity among peripheral and duodenal T-cell subsets revealed varied capacities for mucosal homing and residence. CONCLUSIONS: The breadth of duodenal cellular responses was not reflected peripherally. The direct evaluation of mucosal immune defense may yield functional correlates of protection and could provide insight into mechanisms that may be manipulated to enhance vaccine immunogenicity.


Asunto(s)
Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD8-positivos/inmunología , Mucosa Intestinal/inmunología , Polisacáridos Bacterianos/inmunología , Salmonella typhi/inmunología , Vacunas Tifoides-Paratifoides/inmunología , Administración Oral , Adulto , Anticuerpos Antibacterianos/inmunología , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Inmunidad Celular , Inmunidad Humoral , Inmunogenicidad Vacunal , Masculino , Orthomyxoviridae/inmunología , Vacunas Atenuadas/inmunología , Adulto Joven
20.
J Clin Microbiol ; 54(4): 944-9, 2016 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-26791364

RESUMEN

Current diagnostic tests are ineffective for identifying the etiological pathogen in hospitalized adults with lower respiratory tract infections (LRTIs). The association of pneumococcal colonization with disease has been suggested as a means to increase the diagnostic precision. We compared the pneumococcal colonization rates and the densities of nasal pneumococcal colonization by (i) classical culture and (ii) quantitative real-time PCR (qPCR) targetinglytAin patients with LRTIs admitted to a hospital in the United Kingdom and control patients. A total of 826 patients were screened for inclusion in this prospective case-control study. Of these, 38 patients were recruited, 19 with confirmed LRTIs and 19 controls with other diagnoses. Nasal wash (NW) samples were collected at the time of recruitment. Pneumococcal colonization was detected in 1 patient with LRTI and 3 controls (P= 0.6) by classical culture. By qPCR, pneumococcal colonization was detected in 10 LRTI patients and 8 controls (P= 0.5). Antibiotic usage prior to sampling was significantly higher in the LRTI group than in the control group (19 versus 3;P< 0.001). With a clinically relevant cutoff of >8,000 copies/ml on qPCR, pneumococcal colonization was found in 3 LRTI patients and 4 controls (P> 0.05). We conclude that neither the prevalence nor the density of nasal pneumococcal colonization (by culture and qPCR) can be used as a method of microbiological diagnosis in hospitalized adults with LRTI in the United Kingdom. A community-based study recruiting patients prior to antibiotic therapy may be a useful future step.


Asunto(s)
Técnicas Bacteriológicas/métodos , Portador Sano/diagnóstico , Mucosa Nasal/microbiología , Infecciones Neumocócicas/diagnóstico , Neumonía/diagnóstico , Reacción en Cadena en Tiempo Real de la Polimerasa/métodos , Adulto , Anciano , Anciano de 80 o más Años , Portador Sano/epidemiología , Estudios de Casos y Controles , Femenino , Hospitalización , Hospitales , Humanos , Masculino , Persona de Mediana Edad , Infecciones Neumocócicas/epidemiología , Estudios Prospectivos , Reino Unido
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