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CD8+ T cell dysfunction contributes to severe respiratory viral infection outcomes in older adults. CD8+ T cells are the primary cell type responsible for viral clearance. With increasing age, CD8+ T cell function declines in conjunction with an accumulation of cytotoxic tissue-resident memory (TRM) CD8+ T cells. We sought to elucidate the role of PD-1 signaling on aged CD8+ T cell function and accumulation of CD8+ TRM cells during acute viral respiratory tract infection, given the importance of PD-1 regulating CD8+ T cells during acute and chronic infections. PD-1 blockade or genetic ablation in aged mice yielded improved CD8+ T cell granzyme B production comparable to that in young mice during human metapneumovirus and influenza viral infections. Syngeneic transplant and adoptive transfer strategies revealed that improved granzyme B production in aged Pdcd1-/- CD8+ T cells was primarily cell intrinsic because aged wild-type CD8+ T cells did not have increased granzyme B production when transplanted into a young host. PD-1 signaling promoted accumulation of cytotoxic CD8+ TRM cells in aged mice. PD-1 blockade of aged mice during rechallenge infection resulted in improved clinical outcomes that paralleled reduced accumulation of CD8+ TRM cells. These findings suggest that PD-1 signaling impaired CD8+ T cell granzyme B production and contributed to CD8+ TRM cell accumulation in the aged lung. These findings have implications for future research investigating PD-1 checkpoint inhibitors as a potential therapeutic option for elderly patients with severe respiratory viral infections.
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Infecções Respiratórias , Viroses , Animais , Humanos , Camundongos , Linfócitos T CD8-Positivos , Granzimas , Inibidores de Checkpoint Imunológico , Receptor de Morte Celular Programada 1RESUMO
Human metapneumovirus (HMPV) is a leading cause of respiratory infection in adults >65 y. Nearly all children worldwide are seropositive for HMPV by age 5 y, but reinfections occur throughout life, and there is no licensed vaccine. Recurrent HMPV infection is mild and self-resolving in immunocompetent individuals. However, elderly individuals develop severe respiratory disease on HMPV reinfection that leads to a high risk for morbidity and mortality. In this study, we developed a mouse model to mirror HMPV reinfection in elderly humans. C57BL/6J mice were infected with HMPV at 6-7 wk old, aged in-house, and rechallenged with high-dose virus at 70 wk. Aged rechallenged mice had profound weight loss similar to primary infected mice, increased lung histopathology, and accumulated cytotoxic CD8+CD44+CD62L-CD69+CD103+ memory cells despite having undetectable lung virus titer. When aged mice 14 mo postinfection (p.i.) or young mice 5 wk p.i. were restimulated with HMPV cognate Ag to mimic epitope vaccination, aged mice had an impaired CD8+ memory response. Convalescent serum transfer from young naive or 5 wk p.i. mice into aged mice on day of infection did not protect. Aged mice vaccinated with UV-inactivated HMPV also exhibited diminished protection and poor CD8+ memory response compared with young mice. These results suggest aged individuals with HMPV reinfection have a dysregulated CD8+ memory T cell response that fails to protect and exacerbates disease. Moreover, aged mice exhibited a poor memory response to either epitope peptide or UV-inactivated vaccination, suggesting that aged CD8+ T cell dysfunction presents a barrier to effective vaccination strategies.
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Metapneumovirus , Idoso , Animais , Humanos , Camundongos , Epitopos , Metapneumovirus/fisiologia , Camundongos Endogâmicos C57BL , Gravidade do Paciente , ReinfecçãoRESUMO
AIM: Incorporate species' trait information together with climate projections for associated habitat to assess the potential vulnerability of rodent taxa to climate change. LOCATION: Oaxaca State, Mexico. METHODS: We used a trait-based approach together with climate exposure models to evaluate the vulnerability of rodent species to projected climate conditions in the study region. Vulnerability was estimated based on three factors: (a) Level of climatic exposure that species are projected to experience across their current statewide range; (b) inherent species-specific sensitivity to stochastic events; and (c) species' capacity to cope with climate change effects. We defined species as inherently sensitive if they had any of the following: restricted geographic distribution in Mexico; narrow altitudinal range; low dispersal ability; or long generation length. RESULTS: Vulnerability varied depending on the climate change scenario applied. Under the MPI general circulation model and current emissions trends, by 2099, all species evaluated were projected to have some level of threat (vulnerable for at least one factor), with 4 out of 55 species vulnerable for all three factors, 29 for two factors, and 22 for one factor. Six out of ten rodent species endemic to Oaxaca were vulnerable for two or more factors. We found that species with narrow and restricted-range distributions combined with low adaptive capacity were projected to be particularly vulnerable. MAIN CONCLUSIONS: By including species-specific trait information in climate exposure assessments, researchers can contextualize and enhance their understanding about how climate change is likely to affect individual taxa in an area of interest. As such, studies like this one provide more relevant threat assessment information than exposure analyses alone and serve as a starting point for considering how climatic changes interact with an array of other variables to affect native species across their range.
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ABSTRACT Objective To compare the use of a dynamic surgical guide (PediGuard®) and pilot hole preparation, with the use of a probe and the aid of fluoroscopy in osteoporotic or osteopenic patients undergoing pedicular fixation of the thoracic or lumbar spine. Methods One hundred and eight patients were randomized. A pilot hole was prepared with the dynamic surgical guide (PediGuard®), or with a probe with the aid of fluoroscopy. A total of 657 vertebral pedicles (120 thoracic and 180 lumbar) were included in the study. The parameters used for the comparison were: accuracy of the pedicular screw, number of fluoroscopic shots, and change in intraoperative trajectory of the perforation after detecting pedicle wall rupture. Results In the group with use of the dynamic surgical guide, malpositioning of the pedicle screws was observed in 8 (2.6%) patients and intraoperative change of perforation trajectory in 12 (4%) patients, and there were 52 fluoroscopic shots. In the group without use of the dynamic surgical guide (PediGuard®), misplacement of the pedicle screws was observed in 33 (11%) patients and intraoperative change of perforation trajectory in 47 (13.2%) patients, and there were 136 fluoroscopic shots. Conclusion The use of the dynamic surgical guide (PediGuard®) in patients with osteoporosis or osteopenia enabled more accurate placement of pedicular screws, with less change in the intraoperative course of the perforation and less intraoperative radiation. Level of Evidence II; Randomized clinical trial of lesser quality.
RESUMO Objetivo Comparar o uso de um guia cirúrgico dinâmico (PediGuard®) e o preparo de orifício piloto com uma sonda e o auxílio de fluoroscopia em pacientes com osteopenia ou osteoporose submetidos à fixação pedicular da coluna torácica ou lombar. Métodos Cento e oito pacientes foram randomizados. Um orifício piloto foi preparado com o guia cirúrgico dinâmico (PediGuard®) ou com uma sonda com auxílio de fluoroscopia. Foram incluídos no estudo 657 pedículos vertebrais (120 torácicos e 180 lombares). Os parâmetros usados para a comparação foram: acurácia da colocação do parafuso pedicular, número de disparos fluoroscópicos e mudança da trajetória intraoperatória da perfuração depois da detecção de ruptura da parede do pedículo. Resultados No grupo de pacientes em que se usou o guia cirúrgico dinâmico, observou-se mau posicionamento dos parafusos pediculares em oito (2,6%) pacientes e alteração da trajetória intraoperatória da perfuração em 12 (4%) pacientes, com 52 disparos fluoroscópicos. No grupo de pacientes em que o guia cirúrgico dinâmico (PediGuard®) não foi usado o mau posicionamento dos parafusos pediculares foi observado em 33 (11%) pacientes, a mudança intraoperatória da trajetória da perfuração foi vista em 47 (13,2%) pacientes, com 136 disparos fluoroscópicos. Conclusão O uso do guia cirúrgico dinâmico (PediGuard®) em pacientes com osteoporose ou osteopenia permitiu a colocação de parafusos pediculares com maior acurácia, com menor alteração da trajetória intraoperatória da perfuração e menor dose de radiação intraoperatória. Nível de Evidência II; Estudo clínico randomizado de menor qualidade.
RESUMEN Objetivo Comparar el uso de una guía quirúrgica dinámica (PediGuard®) y la preparación del orificio piloto con una sonda y la ayuda de fluoroscopia en pacientes con osteopenia u osteoporosis sometidos a fijación pedicular de la columna torácica o lumbar. Métodos Ciento ocho pacientes fueron asignados aleatoriamente. Se preparó un orificio piloto preparado con la guía quirúrgica dinámica (PediGuard®) o con una sonda con ayuda de fluoroscopia. Se incluyeron en el estudio 657 pedículos vertebrales (120 torácicos y 180 lumbares). Los parámetros utilizados para la comparación fueron: precisión de la colocación del tornillo pedicular, número de disparos del dispositivo de fluoroscopia y cambio en la trayectoria intraoperatoria de la perforación después de la detección de ruptura de la pared del pedículo. Resultados En el grupo de pacientes en el que se utilizó la guía quirúrgica dinámica, se observó mal posicionamiento de los tornillos pediculares en 8 (2,6%) pacientes y cambios de la trayectoria intraoperatoria de la perforación en 12 (4%) pacientes, con 52 disparos del aparato de fluoroscopia. En el grupo de pacientes en los que no se utilizó la guía quirúrgica dinámica (PediGuard®), se observó un mal posicionamiento de los tornillos pediculares en 33 (11%) pacientes, el cambio intraoperatorio de la trayectoria de perforación se observó en 47 (13,2%) pacientes, con 136 disparos fluoroscópicos. Conclusión El uso de la guía quirúrgica dinámica (PediGuard®) en pacientes con osteoporosis u osteopenia permitió la colocación de tornillos pediculares con mayor precisión, menos cambios en la trayectoria intraoperatoria de la perforación y dosis más baja de radiación intraoperatoria. Nivel de Evidencia II; Ensayo clínico aleatorizado de menor calidad.
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Humanos , Válvulas de Orifício , Doenças Ósseas Metabólicas , Parafusos Ósseos , FluoroscopiaRESUMO
OBJECTIVE: To define the incidence and outcome of acute kidney injury (AKI) in pediatrics using data collected from a national electronic alert system. STUDY DESIGN: A prospective national cohort study was undertaken to collect data on all cases of pediatric AKI, excluding neonates, identified by an e-alert, from April 2015 to March 2019. RESULTS: There were 2472 alerts in a total of 1719 patients, giving an incidence of 77.3 per 100â000 person-years. Of the patients, 84.2% of all AKI were stage 1 and 58.3% occurred with a triggering creatinine within the reference range. The incidence of AKI was associated with measures of social deprivation. Thirty-day mortality was 1.7% but was significantly higher in hospital-acquired AKI (2.1%), compared with community-acquired AKI (0.8%, P < .001) and was associated with the severity of AKI at presentation. A significant proportion of patients had no repeat measure of creatinine (39.8%). This was higher in community-acquired AKI (69.7%) compared with hospital-acquired AKI (43.0%, P < .001), and higher in patients alerting with patients triggering with a creatinine within the reference range (48.4% vs 24.5%, P < .001). The majority of patients (84.7%) experienced only 1 AKI episode. Repeated episodes of AKI were associated with increased 30-mortaltiy (11.6% vs 4.6%, P < .001) and higher residual renal impairment (13.3% vs 5.4%, P < .001). CONCLUSIONS: The results suggest that the significance of the alert is missed in many cases reflecting that a large proportion of cases represent modest elevations in serum creatinine (SCr), triggered by a SCr level that may be interpreted as being normal despite a significant increase from the baseline for the patient.
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Injúria Renal Aguda/diagnóstico , Injúria Renal Aguda/epidemiologia , Creatinina/sangue , Registros Eletrônicos de Saúde , Valores Críticos Laboratoriais , Injúria Renal Aguda/sangue , Criança , Estudos de Coortes , Feminino , Humanos , Incidência , Masculino , Recidiva , Índice de Gravidade de DoençaRESUMO
Acute flaccid myelitis is a debilitating illness characterized by acute onset of limb weakness, with one or more spinal segments displaying magnetic resonance imaging-confirmed gray matter lesions. Since the first outbreak in 2014, tracking by the Centers for Disease Control and Prevention has demonstrated biennial epidemics in the United States, with a current outbreak occurring in 2018. The cases of 3 children with acute flaccid myelitis who were initially thought to have common nonneurologic diagnoses are presented. Emergency physicians need to be vigilant to recognize the subtleties of acute flaccid myelitis because the illness progression is rapid and therapy is nuanced.
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Viroses do Sistema Nervoso Central/diagnóstico , Mielite/diagnóstico , Doenças Neuromusculares/diagnóstico , Pré-Escolar , Diagnóstico Diferencial , Serviço Hospitalar de Emergência/estatística & dados numéricos , Feminino , Humanos , Lactente , Imageamento por Ressonância Magnética , Masculino , PennsylvaniaRESUMO
Photosynthetic productivity is a key determinant of the abundance and distribution of biodiversity around the world. The effect of this productivity on the distribution patterns of mammals is frequently invoked; however, it is seldom measured directly. In this study, we used Sherman live traps set in dry and rainy seasons across a 2300-m elevation gradient in southwestern Mexico to assess small rodent species distributions, and to relate these patterns to habitat structure, climate, and a well-accepted measure of photosynthetic productivity: the normalized difference vegetation index (NDVI). While habitat structure and climate helped explain some of the patterns observed, NDVI proved to be the most important contributing variable for most of the distribution models. We also found that partitioning the gradient-distribution model by trapping season revealed strong differences in terms of the effect of NDVI and the other explanatory variables. For example, lower elevations were associated with seasonal and year-round reductions in rodent diversity and were composed almost exclusively of granivore-based species assemblages. By contrast, the middle and upper elevations were more species rich, less affected by seasonality, and characterized by omnivorous species. Our results suggest that the positive productivity-diversity relationship found may be due, at least in part, to increased food resources and niche opportunities at more productive elevations. Increased diversity at the higher elevations may also be partially due to reductions in competition that result from productivity increases, as well as from the broader spectrum of feeding guild representation that it and the lack of seasonality allow.
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Biodiversidade , Roedores , Animais , Ecossistema , México , Estações do AnoRESUMO
BACKGROUND: Influenza C virus (ICV) is associated with acute respiratory illness. Yet ICV remains under recognized, with most previous studies using only culture to identify cases. OBJECTIVES: To develop a sensitive and specific real-time RT-PCR assay for ICV that allows for rapid and accurate detection in a clinical or research setting. STUDY DESIGN: Multiple ICV sequences obtained from GenBank were analyzed, including 141 hemagglutinin-esterase (HE), 106 matrix (M), and 97 nucleoprotein (NP) sequences. Primers and probes were designed based on conserved regions. Multiple primer-probe sets were tested against multiple ICV strains. RESULTS: The ICV M and NP genes offered the most conserved sequence regions. Primers and probes based on newer sequence data offered enhanced detection of ICV, especially for low titer specimens. An NP-targeted assay yielded the best performance and was capable of detecting 10-100 RNA copies per reaction. The NP assay detected multiple clinical isolates of ICV collected in a field epidemiology study conducted in Peru. CONCLUSIONS: We report a new real-time RT-PCR assay for ICV with high sensitivity and specificity.
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Gammainfluenzavirus/isolamento & purificação , Influenza Humana/diagnóstico , Influenza Humana/virologia , Técnicas de Diagnóstico Molecular/métodos , Reação em Cadeia da Polimerase em Tempo Real/métodos , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos , Pré-Escolar , Feminino , Humanos , Lactente , Gammainfluenzavirus/genética , Masculino , Peru , Sensibilidade e EspecificidadeRESUMO
A 27-year-old man with OSA, posttraumatic stress disorder, and chronic mechanical back pain presented with a 3-day history of acute atraumatic worsening of his low back pain as well as right groin numbness that was exacerbated by walking. He also complained of bilateral leg "heaviness," pain, and swelling, all becoming so severe that he rented a wheelchair for mobility.
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Dor Aguda/etiologia , Circulação Colateral , Edema/etiologia , Dor Lombar/etiologia , Malformações Vasculares/complicações , Veia Cava Inferior/anormalidades , Trombose Venosa/complicações , Adulto , Humanos , Perna (Membro) , Masculino , Limitação da Mobilidade , Tomografia Computadorizada por Raios X , Malformações Vasculares/diagnóstico por imagem , Veia Cava Inferior/diagnóstico por imagem , Trombose Venosa/diagnóstico , Cadeiras de RodasRESUMO
BACKGROUND AND OBJECTIVE: Conscientious objection to abortion, clinicians' refusal to perform legal abortions because of their religious or moral beliefs, has been the subject of increasing debate among bioethicists, policymakers, and public health advocates in recent years. Conscientious objection policies are intended to balance reproductive rights and clinicians' beliefs. However, in practice, clinician objection can act as a barrier to abortion access-impinging on reproductive rights, and increasing unsafe abortion and related morbidity and mortality. There is little information about conscientious objection from a medical or public health perspective. A quantitative instrument is needed to assess prevalence of conscientious objection and to provide insight on its practice. This paper describes the development of a survey instrument to measure conscientious objection to abortion provision. METHODS: A literature review, and in-depth formative interviews with stakeholders in Colombia were used to develop a conceptual model of conscientious objection. This model led to the development of a survey, which was piloted, and then administered, in Ghana. RESULTS: The model posits three domains of conscientious objection that form the basis for the survey instrument: 1) beliefs about abortion and conscientious objection; 2) actions related to conscientious objection and abortion; and 3) self-identification as a conscientious objector. CONCLUSIONS: The instrument is intended to be used to assess prevalence among clinicians trained to provide abortions, and to gain insight on how conscientious objection is practiced in a variety of settings. Its results can inform more effective and appropriate strategies to regulate conscientious objection.
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Aborto Induzido/psicologia , Médicos/psicologia , Recusa em Tratar/estatística & dados numéricos , Atitude do Pessoal de Saúde , Colômbia , Consciência , Gana , Humanos , Modelos Teóricos , Inquéritos e QuestionáriosRESUMO
We examined nasopharyngeal pneumococcal colonization density patterns surrounding acute respiratory illnesses (ARI) in young children in Peru. Pneumococcal densities were dynamic, gradually increasing leading up to an ARI, peaking during the ARI, and decreasing after the ARI. Rhinovirus co-infection was associated with higher pneumococcal densities.
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Nasofaringe/microbiologia , Infecções Pneumocócicas/epidemiologia , Infecções Pneumocócicas/microbiologia , Infecções Respiratórias/epidemiologia , Infecções Respiratórias/microbiologia , Streptococcus pneumoniae/isolamento & purificação , Doença Aguda , Carga Bacteriana , Pré-Escolar , Estudos Transversais , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Peru/epidemiologia , Infecções Pneumocócicas/prevenção & controle , Vacinas Pneumocócicas/imunologia , Vigilância da População , Infecções Respiratórias/prevenção & controle , Fatores de Risco , Streptococcus pneumoniae/imunologiaRESUMO
BACKGROUND: Few studies have described patterns of transmission of viral acute respiratory infections (ARI) in children in developing countries. We examined the spatial and temporal spread of viral ARI among young children in rural Peruvian highland communities. Previous studies have described intense social interactions in those communities, which could influence the transmission of viral infections. METHODS: We enrolled and followed children <3 years of age for detection of ARI during the 2009 to 2011 respiratory seasons in a rural setting with relatively wide geographic dispersion of households and communities. Viruses detected included influenza, respiratory syncytial virus (RSV), human metapneumovirus and parainfluenza 2 and 3 viruses (PIV2, PIV3). We used geospatial analyses to identify specific viral infection hot spots with high ARI incidence. We also explored the local spread of ARI from index cases using standard deviational ellipses. RESULTS: Geospatial analyses revealed hot spots of high ARI incidence around the index cases of influenza outbreaks and RSV outbreak in 2010. Although PIV3 in 2009 and PIV2 in 2010 showed distinct spatial hot spots, clustering was not in proximity to their respective index cases. No significant aggregation around index cases was noted for other viruses. Standard deviational ellipse analyses suggested that influenza B and RSV in 2010, and human metapneumovirus in 2011 spread temporally in alignment with the major road network. CONCLUSIONS: Despite the geographic dispersion of communities in this rural setting, we observed a rapid spread of viral ARI among young children. Influenza strains and RSV in 2010 had distinctive outbreaks arising from their index cases.
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Infecções Respiratórias/epidemiologia , População Rural/estatística & dados numéricos , Viroses/epidemiologia , Doença Aguda , Altitude , Pré-Escolar , Características da Família , Feminino , Humanos , Lactente , Masculino , Peru/epidemiologia , Estudos Prospectivos , Infecções Respiratórias/virologia , Análise Espaço-Temporal , Viroses/virologiaRESUMO
OBJECTIVES: Electroconvulsive therapy (ECT) has dramatically reduced musculoskeletal complications when carried out with muscle relaxants under general anesthesia. However, seizure quality can be affected by the depth of anesthesia and choice of anesthetic agent. The purpose of this study was to describe a general anesthetic technique for ECT by using laryngeal mask, bispectral index (BIS), and muscle relaxant monitoring. METHODS: Twenty-one patients, between ages 18 and 70 years (American Society of Anesthesiologists physical status I-III), who underwent a total of 89 sessions of ECT were examined in a retrospective study. Anesthesia was induced by use of propofol (1.0 mg/kg) followed by cisatracurium (0.2 mg/kg). The BIS, train-of-four, and end-tidal carbon dioxide were all monitored continuously. A laryngeal mask airway was used to maintain and protect the airway during the procedure. Electroconvulsive therapy stimuli were applied bilaterally when the train-of-four was assessed as being zero and BIS scores were 70. All patients then received 5 µg sufentanil and 2 mg midazolam, while titrated to maintain the BIS value at 40 to 50, before the muscle relaxation exhibited complete recovery. RESULTS: The mean duration of treatment process takes approximately 82.5 minutes. Mean (SD) seizure length was 58.8 (28.3) seconds, with 4.5% incidence of restimulation per treatment. Incidence of awareness was 0%. No patients exhibited delirium, nausea, vomiting, or myalgia in the postseizure phase. CONCLUSIONS: Bispectral index monitoring of the depth of anesthesia may have improved seizure quality, and awareness did not occur.
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Anestesia Geral , Atracúrio/análogos & derivados , Monitores de Consciência , Eletroconvulsoterapia/métodos , Máscaras Laríngeas , Fármacos Neuromusculares não Despolarizantes , Adolescente , Adulto , Idoso , Anestesia Geral/efeitos adversos , Atracúrio/efeitos adversos , Dióxido de Carbono/sangue , Eletroconvulsoterapia/efeitos adversos , Feminino , Humanos , Consciência no Peroperatório , Masculino , Pessoa de Meia-Idade , Fármacos Neuromusculares não Despolarizantes/efeitos adversos , Segurança do Paciente , Estudos Retrospectivos , Convulsões/fisiopatologia , Adulto JovemRESUMO
INTRODUCTION: The disease burden and risk factors for respiratory syncytial virus (RSV) and human metapneumovirus (MPV) infections among children living in remote, rural areas remain unclear. MATERIALS AND METHODS: We conducted a prospective, household-based cohort study of children aged <3 years living in remote rural highland communities in San Marcos, Cajamarca, Peru. Acute respiratory illnesses (ARI), including lower respiratory tract infection (LRTI), were monitored through weekly household visits from March 2009 through September 2011. Nasal swabs collected during ARI/LRTI were tested for RSV, MPV, and other respiratory viruses using real-time RT-PCR. Incidence rates and rate ratios were calculated using mixed effects Poisson regression. RESULTS: Among 892 enrolled children, incidence rates of RSV and MPV ARI were 30 and 17 episodes per 100 child-years, respectively. The proportions of RSV and MPV ARI that presented as LRTI were 12.5% and 8.9%, respectively. Clinic visits for ARI and hospitalizations were significantly more frequent (all p values <0.05) among children with RSV (clinic 41% and hospital 5.3%) and MPV ARI (38% and 3.5%) when compared with other viral infections (23% and 0.7%) and infections without virus detected (24% and 0.6%). In multivariable analysis, risk factors for RSV detection included younger age (RR 1.02, 95% CI: 1.00-1.03), the presence of a smoker in the house (RR 1.63, 95% CI: 1.12-2.38), residing at higher altitudes (RR 1.93, 95% CI: 1.25-3.00 for 2nd compared to 1st quartile residents; RR 1.98, 95% CI: 1.26-3.13 for 3rd compared to 1st quartile residents). Having an unemployed household head was significantly associated with MPV risk (RR 2.11, 95% CI: 1.12-4.01). CONCLUSION: In rural high altitude communities in Peru, childhood ARI due to RSV or MPV were common and associated with higher morbidity than ARI due to other viruses or with no viral detections. The risk factors identified in this study may be considered for interventional studies to control infections by these viruses among young children from developing countries.
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Infecções por Paramyxoviridae/epidemiologia , Infecções por Vírus Respiratório Sincicial/epidemiologia , Criança , Pré-Escolar , Feminino , Humanos , Incidência , Lactente , Recém-Nascido , Masculino , Metapneumovirus , Análise Multivariada , Peru/epidemiologia , Distribuição de Poisson , Estudos Prospectivos , Vírus Sincicial Respiratório Humano , Fatores de Risco , População RuralRESUMO
BACKGROUND: Viruses are commonly detected in children with acute respiratory illnesses (ARIs) and in asymptomatic children. Longitudinal studies of viral detections during asymptomatic periods surrounding ARI could facilitate interpretation of viral detections but are currently scant. METHODS: We used reverse transcription polymerase chain reaction to analyze respiratory samples from young Andean children for viruses during asymptomatic periods within 8-120 days of index ARI (cough or fever). We compared viral detections over time within children and explored reverse transcription polymerase chain reaction cycle thresholds (CTs) as surrogates for viral loads. RESULTS: At least 1 respiratory virus was detected in 367 (43%) of 859 samples collected during asymptomatic periods, with more frequent detections in periods with rhinorrhea (49%) than those without (34%, P < 0.001). Relative to index ARI with human rhinovirus (HRV), adenovirus (AdV), respiratory syncytial virus (RSV) and parainfluenza virus detected, the same viruses were also detected during 32, 22, 10 and 3% of asymptomatic periods, respectively. RSV was only detected 8-30 days after index RSV ARI, whereas HRV and AdV were detected throughout asymptomatic periods. Human metapneumovirus and influenza were rarely detected during asymptomatic periods (<3%). No significant differences were observed in the CT for HRV or AdV during asymptomatic periods relative to ARI. For RSV, CTs were significantly lower during ARI relative to the asymptomatic period (P = 0.03). CONCLUSIONS: These findings indicate that influenza, human metapneumovirus, parainfluenza virus and RSV detections in children with an ARI usually indicate a causal relationship. When HRV or AdV is detected during ARI, the causal relationship is less certain.
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Infecções Respiratórias/diagnóstico , Infecções Respiratórias/virologia , Carga Viral/métodos , Vírus/genética , Criança , Humanos , Peru , Distribuição Aleatória , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Vírus/isolamento & purificaçãoRESUMO
BACKGROUND: Respiratory syncytial virus (RSV) is a major cause of respiratory infections in children. Palivizumab (PZ) is the only RSV-specific immunoprophylaxis approved by the U.S. Food and Drug Administration. Mutations leading to amino acid substitutions in the PZ binding site of the RSV F protein have been associated with breakthrough RSV infections in patients receiving PZ. OBJECTIVE: To detect PZ resistance conferring mutations in RSV strains from children who received PZ. STUDY DESIGN: Children aged ≤ 24 months on October 31 who were hospitalized or had outpatient visits for respiratory illness and/or fever during October-May 2001-2008 in 3 US counties were included. PZ receipt was obtained from parent interviews and medical records among children subsequently infected with RSV. Archived nasal/throat swab specimens were tested for RSV by real-time RT-PCR. The coding region of the PZ binding site of the RSV F protein was sequenced using both Sanger and pyrosequencing methods. RESULTS: Of 8762 enrolled children, 375 (4.3%) were tested for RSV and had a history of PZ receipt, of which 56 (14.9%) were RSV-positive and 45 of these had available archived specimens. Molecular typing identified 42 partial F gene sequences in specimens from 39 children: 19 single RSV subgroup A, 17 subgroup B and 3 mixed infections. Nucleotide substitutions were identified in 12/42 (28.6%) RSV strains. PZ resistance mutations were identified in 4 (10.2%) of the 39 children, of which one had documented PZ receipt. CONCLUSIONS: Although RSV PZ resistance mutations were infrequent, most RSV-associated illnesses in children with a history of PZ receipt were not due to strain resistance.
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Antivirais/uso terapêutico , Palivizumab/uso terapêutico , Infecções por Vírus Respiratório Sincicial/prevenção & controle , Infecções por Vírus Respiratório Sincicial/virologia , Vírus Sinciciais Respiratórios/efeitos dos fármacos , Vírus Sinciciais Respiratórios/genética , Antivirais/farmacologia , Criança , Pré-Escolar , Farmacorresistência Viral/genética , Feminino , Humanos , Masculino , Mutação , Palivizumab/farmacologia , Análise de Sequência de DNA , Fatores de Tempo , Estados UnidosRESUMO
OBJECTIVE: To determine the effectiveness of a pedicle probe to anticipate an impending breach and allow redirection during placement of a pilot pedicle hole. METHODS: Purposely four cortical wall sites were drilled: medial and lateral pedicle wall, and lateral and anterior wall of the vertebral body. The surgeon stopped probing when the sound changed, suggesting abutment against the cortical wall ("anticipation" of impending breach). A fluoroscopy image was then obtained. The surgeon then advanced the PediGuard through the cortex until the sound changed, indicating a breach. In the second part of the study three probes were used: 1) DSG (PediGuard) with curved tip with electronics ON; 2) DSG with electronics OFF; 3) standard Lenke probe. After the images were taken, the operating surgeon (blinded to x-rays) was instructed to redirect and continue drilling into the vertebral body. RESULTS: The surgeon accurately anticipated 60 of 75 (80%) of the breaches, 17 of 19 (89%) in the medial pedicle wall. In the second part of the study the DSG with electronics ON was superior to the DSG with electronics OFF as well as the standard Lenke probe (100% vs. 90% vs. 79%, p = 0.0191). CONCLUSION: Successful redirection by passing the pedicle probes into the vertebral body without a breach after anticipation of an impending pedicle wall breach occurred in 100% of the drillings when done with the DSG with the electronics ON vs only 84% when there was no electronic feedback. .
OBJETIVO: Avaliar a efetividade da sonda pedicular para prever a rotura iminente e permitir o redirecionamento durante o posicionamento de orifício piloto no pedículo. MÉTODOS: Intencionalmente, foram feitos quatro orifícios na parede cortical: parede medial e lateral do pedículo e parede lateral e anterior do corpo vertebral. O cirurgião parava a sondagem à mudança do som, que sugeria a proximidade da parede cortical ("previsão" de rotura iminente). A imagem por fluoroscopia era obtida. A seguir, o cirurgião avançava a sonda PediGuard através do osso cortical até a alteração do som, que indicava a rotura. Na segunda parte do estudo foram utilizadas três sondas: GCD (PediGuard) com ponta curva ligada, PediGuard curva desligada e sonda Lenke padrão. Depois que as radiografias eram feitas, o cirurgião (sem ver as imagens) era instruído a redirecionar e a continuar perfurando o corpo vertebral. RESULTADOS: O cirurgião previu com precisão 60 das 75 (80%) roturas, 17 de 19 (89%) na parede medial do pedículo. Na segunda parte do estudo, o guia cirúrgico dinâmico ligado foi superior à desligado, assim como à sonda Lenke padrão (100% vs. 90% vs. 79%, p = 0,0191). CONCLUSÃO: O redirecionamento bem-sucedido da sonda pedicular no interior do corpo vertebral, sem rotura devido à previsão de rotura iminente da parede do pedículo ocorreu em 100% das perfurações com a utilização do o guia cirúrgico dinâmico com o dispositivo ligado, em comparação com 84% das perfurações com o dispositivo desligado. .
OBJETIVO: Evaluar la efectividad de la sonda pedicular para prever la rotura inminente y permitir el redireccionamiento durante el posicionamiento de orificio piloto en el pedículo. MÉTODOS: Intencionalmente, fueron hechos cuatro orificios en la pared cortical: pared medial y lateral del pedículo y pared lateral y anterior del cuerpo vertebral. El cirujano paraba el sondeo al cambiar el sonido, que sugería la proximidad de la pared cortical ("previsión" de rotura inminente). Era obtenida imagen por fluoroscopia. A seguir, el cirujano avanzaba la sonda PediGuard a través del hueso cortical hasta la alteración del sonido, que indicaba la rotura. En la segunda parte del estudio fueron utilizadas tres sondas: ECMT (PediGuard) con punta curva encendida, PediGuard curva apagada y sonda Lenke estándar. Después que las radiografías eran realizadas, el cirujano (sin ver las imágenes) era instruido a redireccionar y a continuar perforando el cuerpo vertebral. RESULTADOS: El cirujano previno con precisión 60 de las 75 (80%) roturas, 17 de 19 (89%) en la pared medial del pedículo. En la segunda parte del estudio, la sonda ECMT encendida fue superior a la apagada, así como a la sonda Lenke estándar (100% vs. 90% vs. 79%, p = 0,0191). CONCLUSIÓN: El redireccionamiento exitoso de la sonda pedicular en el interior del cuerpo vertebral, sin rotura debido a la previsión de rotura inminente de la pared del pedículo ocurrió en 100% de las perforaciones con el uso de la sonda ECMT con el dispositivo encendido, en comparación con 84% de las perforaciones con el dispositivo apagado. .
Assuntos
Procedimentos Cirúrgicos Operatórios/métodos , Fusão Vertebral/instrumentação , Fluoroscopia , Parafusos PedicularesRESUMO
OBJECTIVE: To investigate the effects of intravenous administration of dexamethasone on early postoperative cognitive dysfunction (POCD). METHODS: In this prospective randomized trial, 1000 patients with facial spasm undergoing microvascular decompression (MVD) were randomly assigned to receive normal sodium (Dex-0 group, n=333), dexamethasone 0.1 mg/kg (Dex-1 group, n=333), or dexamethasone 0.2 mg/kg (Dex-2 group, n=334). Exclusion criteria included: a history of neurologic or mental disease, renal failure, active liver disease, cardiac or pulmonary dysfunction, endocrine, metabolic, or peptic ulcer disease, a history of past surgery, <6 years of schooling, inability to complete neuropsychological testing, visual dysfunction, and auditory dysfunction. Patients were also excluded at any point if additional steroid was required. Propofol and sufentanil were administered for anesthetic induction, whereas propofol and remifentanil were given for maintenance of anesthesia. A battery of 9 neuropsychological tests was administered preoperatively and the on day 5 postoperatively. A postoperative deficit was defined as a postoperative decrement to preoperative score of >1SD on any test. Patients who experienced >2 deficits were considered to have experienced early POCD. RESULTS: Nine hundred and fifty-four patients completed both preoperative and postoperative neuropsychological testing. Within the 3 groups: Dex-0 group, n=319; Dex-1 group, n=320 and Dex-2, n=315. POCD occurred in 71 patients (22.3%) in the Dex-0 group, in 66 patients (20.6%) in the Dex-1 group, and 99 patients (31.4%) in the Dex-2 group. POCD was significant among the 3 groups (P=0.003). Partitions of χ method was applied for multiple comparisons showing that Dex-2 group was significantly different from Dex-1 and Dex-0 groups. CONCLUSIONS: Administration of higher dose of dexamethasone (0.2 mg/kg) increases the incidence of POCD in the early postoperative period after microvascular decompression under general anesthesia.
Assuntos
Transtornos Cognitivos/induzido quimicamente , Dexametasona/efeitos adversos , Hipnóticos e Sedativos/efeitos adversos , Complicações Pós-Operatórias/induzido quimicamente , Adulto , Anestesia , Transtornos Cognitivos/epidemiologia , Dexametasona/administração & dosagem , Feminino , Humanos , Hipnóticos e Sedativos/administração & dosagem , Masculino , Cirurgia de Descompressão Microvascular/efeitos adversos , Pessoa de Meia-Idade , Testes Neuropsicológicos , Complicações Pós-Operatórias/epidemiologia , Estudos ProspectivosRESUMO
BACKGROUND: Animal models suggest that influenza infection favors nasopharyngeal acquisition of pneumococci. We assessed this relationship with influenza and other respiratory viruses in young children. METHODS: A case-control study was nested within a prospective cohort study of acute respiratory illness (ARI) in Andean children <3 years of age (RESPIRA-PERU study). Weekly household visits were made to identify ARI and obtain nasal swabs for viral detection using real-time reverse-transcription polymerase chain reaction. Monthly nasopharyngeal (NP) samples were obtained to assess pneumococcal colonization. We determined whether specific respiratory viral ARI episodes occurring within the interval between NP samples increased the risk of NP acquisition of new pneumococcal serotypes. RESULTS: A total of 729 children contributed 2128 episodes of observation, including 681 pneumococcal acquisition episodes (new serotype, not detected in prior sample), 1029 nonacquisition episodes (no colonization or persistent colonization with the same serotype as the prior sample), and 418 indeterminate episodes. The risk of pneumococcal acquisition increased following influenza-ARI (adjusted odds ratio [AOR], 2.19; 95% confidence interval [CI], 1.02-4.69) and parainfluenza-ARI (AOR, 1.86; 95% CI, 1.15-3.01), when compared with episodes without ARI. Other viral infections (respiratory syncytial virus, human metapneumovirus, human rhinovirus, and adenovirus) were not associated with acquisition. CONCLUSIONS: Influenza and parainfluenza ARIs appeared to facilitate pneumococcal acquisition among young children. As acquisition increases the risk of pneumococcal diseases, these observations are pivotal in our attempts to prevent pneumococcal disease.
Assuntos
Influenza Humana/virologia , Nasofaringe/microbiologia , Orthomyxoviridae/fisiologia , Infecções por Paramyxoviridae/virologia , Paramyxoviridae/fisiologia , Infecções Respiratórias/virologia , Streptococcus pneumoniae/isolamento & purificação , Estudos de Casos e Controles , Pré-Escolar , Estudos de Coortes , Feminino , Humanos , Lactente , Recém-Nascido , Influenza Humana/microbiologia , Masculino , Interações Microbianas , Infecções por Paramyxoviridae/microbiologia , Peru , Estudos Prospectivos , Infecções Respiratórias/microbiologia , Fatores de Risco , Sorotipagem , Streptococcus pneumoniae/classificaçãoRESUMO
BACKGROUND: The Respiratory Infections in Andean Peruvian Children (RESPIRA-PERU) study enrolled children who participated in a community-cluster randomized trial of improved stoves, solar water disinfection, and kitchen sinks (IHIP trial) and children from additional Andean households. We quantified the burden of influenza-associated acute respiratory illness (ARI) in this household-based cohort. METHODS: From May 2009 to September 2011, we conducted active weekly ARI surveillance in 892 children age <3 years, of whom 272 (30.5%) had participated in the IHIP trial. We collected nasal swabs during ARI, tested for influenza and other respiratory viruses by RT-PCR, and determined influenza incidence and risk factors using mixed-effects regression models. RESULTS: The overall incidence of influenza-associated ARI was 36.6/100 child-years; incidence of influenza A, B, and C was 20.5, 8.7, and 5.2/100 child-years, respectively. Influenza C was associated with fewer days of subjective fever (median 1 vs. 2) and malaise (median 0 vs. 2) compared to influenza A. Non-influenza ARI also resulted in fewer days of fever and malaise, and fewer healthcare visits than influenza A-associated ARI. Influenza incidence varied by calendar year (80% occurred in the 2010 season) and IHIP trial participation. Among households that participated in the IHIP trial, influenza-associated ARI incidence was significantly lower in intervention than in control households (RR 0.40, 95% CI: 0.20-0.82). CONCLUSIONS: Influenza burden is high among Andean children. ARI associated with influenza A and B had longer symptom duration and higher healthcare utilization than influenza C-associated ARI or non-influenza ARI. Environmental community interventions may reduce influenza morbidity.