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1.
Am J Emerg Med ; 59: 85-93, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35816837

RESUMO

INTRODUCTION: Blood pressure (BP) monitoring and management is essential in the treatment of acute aortic disease (AoD). Previous studies had shown differences between invasive arterial BP monitoring (ABPM) and non-invasive cuff BP monitoring (CBPM), but not whether ABPM would result in patients' change of clinical management. We hypothesized that ABPM would change BP management in AoD patients. METHODS: This was a prospective observational study of adult patients with AoD admitted to the Critical Care Resuscitation Unit from January 2019 to February 2021. Patients with AoD and both ABPM and CBPM measurements were included. Clinician's BP management goals were assessed in real time before and after arterial catheter placement according to current guidelines. We defined change of management as change of current antihypertensive infusion rate or adding a new agent. We used multivariable logistic and ordinal regressions to determine relevant predictors. RESULTS: We analyzed 117 patients, and 56 (47%) had type A dissection. ABPM was frequently ≥10 mmHg higher than CBPM values. Among 40 (34%) patients with changes in management, 58% (23/40) had [ABPM-CBPM] differences ≥20 mmHg. ABPM prompted increasing current antihypertensive infusion in 68% (27/40) of patients. Peripheral artery disease (OR 13, 95% CI 1.18-50+) was associated with changes in clinical management, and ordinal regression showed hypertension and serum lactate to be associated with differences between ABPM and CBPM. CONCLUSIONS: ABPM was frequently higher than CBPM, resulting in 34% of changes of management, most commonly increasing anti-hypertensive infusion rates.


Assuntos
Doenças da Aorta , Hipertensão , Adulto , Anti-Hipertensivos/uso terapêutico , Doenças da Aorta/complicações , Pressão Arterial , Pressão Sanguínea , Monitorização Ambulatorial da Pressão Arterial/métodos , Humanos , Hipertensão/complicações , Hipertensão/tratamento farmacológico
2.
Aggress Behav ; 46(3): 220-231, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32100888

RESUMO

The present study sought to examine the influence of aggressive behavior, psychopathy, and gender on moral judgments of aggressive transgressions. A two-dimensional conceptualization of aggression was used, such that proactive relational aggression, reactive relational aggression, proactive physical aggression, and reactive physical aggression were treated as distinct subtypes of aggression and also as distinct subtypes of moral judgments of aggression. Participants were 421 emerging adults (215 women). Self-report measures of aggression, psychopathy, and moral judgments were collected. Peer-reports of aggression and psychopathy were obtained from a randomly assigned subsample of 73 participants (46 women) for validity purposes. Unique associations were found between subtypes of aggression and corresponding moral judgments of the same subtypes.


Assuntos
Agressão , Transtorno da Personalidade Antissocial , Julgamento , Princípios Morais , Adulto , Feminino , Humanos , Grupo Associado , Fatores Sexuais
3.
Ann Clin Microbiol Antimicrob ; 18(1): 24, 2019 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-31434563

RESUMO

BACKGROUND: Antimicrobial resistance is a widely recognized public health threat, and stewardship interventions to combat this problem are well described. Less is known about antifungal stewardship (AFS) initiatives and their influence within the United States. The purpose of this study was to evaluate evidence on the impact of AFS interventions on clinical and performance measures. METHODS: A systematic review of English language studies identified in the PubMed and EMBASE databases was performed through November 2017. The review was conducted in accordance with PRISMA. Search terms included antifungal stewardship, antimicrobial stewardship, Candida, candidemia, candiduria, and invasive fungal disease. Eligible studies were those that described an AFS program or intervention occurring in the US and evaluated clinical or performance measures. RESULTS: Fifty-four articles were identified and 13 were included. Five studies evaluated AFS interventions and reported clinical outcomes (mortality and length of stay) and performance measures (appropriate antifungal choice and time to therapy). The remaining eight studies evaluated general stewardship interventions and reported data on antifungal consumption. All studies were single center, quasi-experimental with varying interventions across studies. AFS programs had no impact on mortality (3 of 3 studies), with an overall rate of 27% in the intervention group and 23% in the non-intervention group. Length of stay (5 of 5) was also similar between groups (range, 9-25 vs. 11-22). Time to antifungal therapy improved in 2 of 5 studies, and appropriate choice of antifungal increased in 2 of 2 studies. Antifungal consumption was significantly blunted or reduced following stewardship initiation (8 of 8), although a direct comparison between studies was not possible due to a lack of common units. CONCLUSION: The available evidence suggests that AFS interventions can improve performance measures and decrease antifungal consumption. Although this review did not detect improvements in clinical outcomes, significant adverse outcomes were not reported.


Assuntos
Antifúngicos/uso terapêutico , Gestão de Antimicrobianos/métodos , Uso de Medicamentos/normas , Pesquisa sobre Serviços de Saúde , Infecções Fúngicas Invasivas/tratamento farmacológico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Análise de Sobrevida , Estados Unidos , Adulto Jovem
4.
J Clin Child Adolesc Psychol ; 44(3): 380-92, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25133659

RESUMO

The development and course of the subtypes of peer victimization is a relatively understudied topic despite the association of victimization with important developmental and clinical outcomes. Moreover, understanding potential predictors, such as peer rejection and emotion regulation, in early childhood may be especially important to elucidate possible bidirectional pathways between relational and physical victimization and rejection. The current study (N = 97) was designed to explore several gaps and limitations in the peer victimization and peer rejection literature. In particular, the prospective associations between relational and physical victimization and peer rejection over the course of 3.5 months during early childhood (i.e., 3 to 5 years old) were investigated in an integrated model. The study consisted of 97 (42 girls) preschool children recruited from four early childhood schools in the northeast of the United States. Using observations, research assistant report, and teacher report, relational and physical aggression, relational and physical victimization, peer rejection, and emotion regulation were measured in a short-term longitudinal study. Path analyses were conducted to test the overall hypothesized model. Peer rejection was found to predict increases in relational victimization. In addition, emotion regulation was found to predict decreases in peer rejection and physical victimization. Implications for research and practice are discussed, including teaching coping strategies for peer rejection and emotional distress.


Assuntos
Agressão/psicologia , Bullying/psicologia , Vítimas de Crime/psicologia , Grupo Associado , Rejeição em Psicologia , Adaptação Psicológica , Criança , Pré-Escolar , Emoções/fisiologia , Feminino , Humanos , Masculino , Estudos Prospectivos , Instituições Acadêmicas
5.
Dev Psychopathol ; 26(3): 575-87, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25047285

RESUMO

A short-term longitudinal study during early childhood (N = 301; 155 girls; M = 44.76 months old, SD = 8.20) investigated the prospective associations between peer victimization and aggression subtypes. Specifically, observations of relational and physical victimization as well as teacher reports of the forms (i.e., relational and physical) and functions (i.e., proactive and reactive) of aggression were collected at two time points during an academic year. Within- and between-group gender differences were examined as part of the preliminary analyses. In order to address key study questions, both directions of effect between peer victimization and aggression subtypes were examined. We found that teacher-reported proactive relational aggression predicted decreases in observed relational victimization over time, whereas reactive relational aggression predicted increases in observed relational victimization over time. Ways in which these and other findings extend the literature are discussed.


Assuntos
Agressão/psicologia , Bullying/psicologia , Comportamento Infantil/psicologia , Vítimas de Crime/psicologia , Grupo Associado , Pré-Escolar , Feminino , Humanos , Relações Interpessoais , Masculino , Estudos Prospectivos , Fatores Sexuais
6.
J Exp Child Psychol ; 116(1): 19-36, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23422928

RESUMO

The central goal of this study was to examine the prospective associations between forms (i.e., physical and relational) and functions (i.e., proactive and reactive) of aggressive behavior with social (i.e., peer rejection) and affective (i.e., anger, emotion regulation skills) processes during early childhood (N = 96, mean age = 42.80 months, SD = 7.57). A cross-lagged path analysis revealed that proactive relational aggression was uniquely associated with decreases in peer rejection, whereas reactive relational aggression was associated with increases in peer rejection over time. Proactive relational aggression predicted decreases in anger, whereas reactive relational aggression tended to be associated with increases in anger. Proactive relational aggression uniquely predicted increases in emotion regulation skills, whereas reactive relational aggression tended to be associated with decreases in emotion regulation skills over time. Finally, anger was significantly associated with increases in several subtypes of aggressive behavior. In sum, the findings provide further support for the distinction between subtypes of aggressive behavior in young children.


Assuntos
Afeto/fisiologia , Agressão/psicologia , Comportamento Infantil/psicologia , Comportamento Social , Agressão/fisiologia , Ira/fisiologia , Comportamento Infantil/fisiologia , Pré-Escolar , Emoções/fisiologia , Feminino , Humanos , Masculino , Grupo Associado , Rejeição em Psicologia , Ajustamento Social
7.
West J Emerg Med ; 24(4): 763-773, 2023 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-37527376

RESUMO

INTRODUCTION: Blood pressure measurement is important for treating patients. It is known that there is a discrepancy between cuff blood pressure vs arterial blood pressure measurement. However few studies have explored the clinical significance of discrepancies between cuff (CPB) vs arterial blood pressure (ABP). Our study investigated whether differences in CBP and ABP led to change in management for patients with hypertensive emergencies and factors associated with this change. METHODS: This prospective observational study included adult patients admitted between January 2019-May 2021 to a resuscitation unit with hypertensive emergencies. We defined clinical significance of discrepancies as a discrepancy between CBP and ABP that resulted in change of clinical management. We used stepwise multivariable logistic regression to measure associations between clinical factors and outcomes. RESULTS: Of 212 patients we analyzed, 88 (42%) had change in management. Mean difference between CBP and ABP was 17 milligrams of mercury (SD 14). Increasing the existing rate of antihypertensive infusion occurred in 38 (44%) patients. Higher body mass index (odds ratio [OR] 1.04, 95% confidence Interval [CI] 1.0001-1.08, P-value <0.05) and history of peripheral arterial disease (OR 0.16, 95% CI 0.03-0.97, P-value <0.05) were factors associated with clinical significance of discrepancies. CONCLUSION: Approximately 40% of hypertensive emergencies had a clinical significance of discrepancy warranting management change when arterial blood pressure was initiated. Further studies are necessary to confirm our observations and to investigate the benefit-risk ratio of ABP monitoring.


Assuntos
Hipertensão , Adulto , Humanos , Hipertensão/diagnóstico , Hipertensão/tratamento farmacológico , Emergências , Monitorização Ambulatorial da Pressão Arterial , Determinação da Pressão Arterial/métodos , Cuidados Críticos , Pressão Sanguínea/fisiologia
8.
World J Emerg Med ; 14(3): 173-178, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37152525

RESUMO

BACKGROUND: Blood pressure (BP) monitoring is essential for patient care. Invasive arterial BP (IABP) is more accurate than non-invasive BP (NIBP), although the clinical significance of this difference is unknown. We hypothesized that IABP would result in a change of management (COM) among patients with non-hypertensive diseases in the acute phase of resuscitation. METHODS: This prospective study included adults admitted to the Critical Care Resuscitation Unit (CCRU) with non-hypertensive disease from February 1, 2019, to May 31, 2021. Management plans to maintain a mean arterial pressure >65 mmHg (1 mmHg=0.133 kPa) were recorded in real time for both NIBP and IABP measurements. A COM was defined as a discrepancy between IABP and NIBP that resulted in an increase/decrease or addition/discontinuation of a medication/infusion. Classification and regression tree analysis identified significant variables associated with a COM and assigned relative variable importance (RVI) values. RESULTS: Among the 206 patients analyzed, a COM occurred in 94 (45.6% [94/206]) patients. The most common COM was an increase in current infusion dosages (40 patients, 19.4%). Patients receiving norepinephrine at arterial cannulation were more likely to have a COM compared with those without (45 [47.9%] vs. 32 [28.6%], P=0.004). Receiving norepinephrine (relative variable importance [RVI] 100%) was the most significant factor associated with a COM. No complications were identified with IABP use. CONCLUSION: A COM occurred in 94 (45.6%) non-hypertensive patients in the CCRU. Receiving vasopressors was the greatest factor associated with COM. Clinicians should consider IABP monitoring more often in non-hypertensive patients requiring norepinephrine in the acute resuscitation phase. Further studies are necessary to confirm the risk-to-benefit ratios of IABP among these high-risk patients.

9.
West J Emerg Med ; 23(3): 358-367, 2022 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-35679499

RESUMO

INTRODUCTION: Blood pressure (BP) monitoring is an essential component of sepsis management. The Surviving Sepsis Guidelines recommend invasive arterial BP (IABP) monitoring, although the benefits over non-invasive BP (NIBP) monitoring are unclear. This study investigated discrepancies between IABP and NIBP measurement and their clinical significance. We hypothesized that IABP monitoring would be associated with changes in management among patients with sepsis requiring vasopressors. METHODS: We performed a retrospective study of adult patients admitted to the critical care resuscitation unit at a quaternary medical center between January 1-December 31, 2017. We included patients with sepsis conditions AND IABP monitoring. We defined a clinically significant BP discrepancy (BPD) between NIBP and IABP measurement as a difference of > 10 millimeters of mercury (mm Hg) AND change of BP management to maintain mean arterial pressure ≥ 65 mm Hg. RESULTS: We analyzed 127 patients. Among 57 (45%) requiring vasopressors, 9 (16%) patients had a clinically significant BPD vs 2 patients (3% odds ratio [OR] 6.4; 95% CI: 1.2-30; P = 0.01) without vasopressors. In multivariable logistic regression, higher Sequential Organ Failure Assessment (SOFA) score (OR 1.33; 95% CI: 1.02-1.73; P = 0.03) and serum lactate (OR 1.27; 95% CI: 1.003-1.60, P = 0.04) were associated with increased likelihood of clinically significant BPD. There were no complications (95% CI: 0-0.02) from arterial catheter insertions. CONCLUSION: Among our population of septic patients, the use of vasopressors was associated with increased odds of a clinically significant blood pressure discrepancy between IABP and NIBP measurement. Additionally, higher SOFA score and serum lactate were associated with higher likelihood of clinically significant blood pressure discrepancy. Further studies are needed to confirm our observations and investigate the benefits vs the risk of harm of IABP monitoring in patients with sepsis.


Assuntos
Determinação da Pressão Arterial , Sepse , Adulto , Pressão Sanguínea , Humanos , Lactatos , Estudos Retrospectivos , Sepse/diagnóstico , Vasoconstritores/uso terapêutico
10.
Behav Sci Law ; 29(5): 695-710, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21815200

RESUMO

Two studies investigated potential mediators of the association between relational victimization and relational aggression. Self-report measures of aggressive behavior among peers, exclusivity, hostile attribution biases, and borderline personality disorder (BPD) symptoms were collected. In study 1, participants were 180 female emerging adults (M = 18.82, SD = 1.18). Both exclusivity and hostile attribution biases for relational provocations were found to partially mediate the association between relational victimization and relational aggression. In study 2, participants were 54 female emerging adults (M = 19.16, SD = 1.11). Symptoms of BPD were not found to mediate the association between relational victimization and relational aggression, yet unique associations with relational aggression were observed. The results add to recent research guided by a social process model in which links between victimization and aggression are more clearly understood.


Assuntos
Agressão/psicologia , Hostilidade , Relações Interpessoais , Modelos Psicológicos , Adolescente , Transtorno da Personalidade Borderline/psicologia , Vítimas de Crime/psicologia , Feminino , Humanos , Grupo Associado , Autorrelato , Adulto Jovem
11.
J Commun Disord ; 93: 106145, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34399133

RESUMO

BACKGROUND: After a stroke, it is highly likely that an individual will experience substantial fatigue that can significantly affect recovery and function; stroke survivors also have more than a 50% chance of having at least one speech-language disorder. Current reviews of post-stroke fatigue have not provided evidence focused on speech-language disorders or the potential influence they may have on post-stroke fatigue and related recovery. OBJECTIVES: The aim of this review was to determine how speech-language disorders are represented in post-stroke fatigue research and to catalogue methods used to identify speech-language disorders and measure fatigue. METHODS: A systematic scoping review was conducted to identify studies measuring post-stroke fatigue. To identify these studies, a comprehensive literature search was conducted using relevant databases and grey literature sources, followed by several stages of review that adhered to PRISMA guidelines. We evaluated these studies using pre-established eligibility criteria and extracted data regarding the inclusion/exclusion of persons with speech-language disorders and the assessment methods used. RESULTS: The scoping review analysis was conducted on 161 studies. Of these, 41 (26%) excluded all speech-language disorders, 71 (44%) excluded severe speech-language disorders, and 49 (30%) included participants with speech-language disorders. Of the 120 studies that did not explicitly exclude all speech-language disorders, only 34 were confirmed to report data from at least one person with a speech-language disorder. Further, only 5 studies reported data that could be used to determine a relationship between speech-language disorders and fatigue. CONCLUSIONS: Persons with speech-language disorders are underrepresented in post-stroke fatigue research and very few studies have examined the relationship between post-stroke fatigue and speech-language disorders, limiting conclusions that can be drawn. This is problematic because medical professionals relying on this evidence to guide clinical practice are likely to be treating individuals with co-occurring fatigue and speech-language disorders and the current research does not provide enough information about the potential impact of fatigue on speech-language disorders or vice versa. To bridge this gap, we suggest methods of assessment that could provide ways to more accurately 1) reflect the real population in post-stroke fatigue studies, and 2) measure and document fatigue in post-stroke speech-language disorder studies. We also propose the Filter-Funnel Model of Post-Stroke Fatigue, which considers the role of speech-language disorders and communicative demands in the context of post-stroke fatigue.


Assuntos
Transtornos da Comunicação , Transtornos da Linguagem , Fadiga/etiologia , Humanos , Fala , Fonoterapia
12.
J Bacteriol ; 192(14): 3722-34, 2010 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-20472788

RESUMO

The locus for enterocyte effacement (LEE) is the virulence hallmark of the attaching-and-effacing (A/E) intestinal pathogens, namely, enteropathogenic Escherichia coli, enterohemorrhagic E. coli, and Citrobacter rodentium. The LEE carries more than 40 genes that are arranged in several operons, e.g., LEE1 to LEE5. Expression of the various transcriptional units is subject to xenogeneic silencing by the histone-like protein H-NS. The LEE1-encoded regulator, Ler, plays a key role in relieving this repression at several major LEE promoters, including LEE2 to LEE5. To achieve appropriate intracellular concentrations of Ler in different environments, A/E pathogens have evolved a sophisticated regulatory network to control ler expression. For example, the LEE-encoded GrlA and GrlR proteins work as activator and antiactivator, respectively, of ler transcription. Thus, control of the transcriptional activities of the LEE1 (ler) promoter and the grlRA operon determines the rate of transcription of all of the LEE-encoded virulence factors. To date, only a single promoter has been identified for the grlRA operon. In this study, we showed that the non-LEE-encoded AraC-like regulatory protein RegA of C. rodentium directly stimulates transcription of the grlRA promoter by binding to an upstream region in the presence of bicarbonate ions. In addition, in vivo and in vitro transcription assays revealed a sigma(70) promoter that is specifically responsible for transcription of grlA. Expression from this promoter was strongly repressed by H-NS and its paralog StpA but was activated by Ler. DNase I footprinting demonstrated that Ler binds to a region upstream of the grlA promoter, whereas H-NS interacts specifically with a region extending from the grlA core promoter into its coding sequence. Together, these findings provide new insights into the environmental regulation and differential expressions of the grlR and grlA genes of C. rodentium.


Assuntos
Proteínas de Bactérias/metabolismo , Citrobacter rodentium/genética , Citrobacter rodentium/metabolismo , Regulação Bacteriana da Expressão Gênica/fisiologia , Óperon/genética , Proteínas de Bactérias/genética , Sequência de Bases , Mapeamento Cromossômico , Citrobacter rodentium/patogenicidade , DNA Bacteriano , Regulação Enzimológica da Expressão Gênica/fisiologia , Dados de Sequência Molecular , Bicarbonato de Sódio , Sítio de Iniciação de Transcrição , Transcrição Gênica , Virulência
13.
J Antimicrob Chemother ; 65(5): 974-80, 2010 May.
Artigo em Inglês | MEDLINE | ID: mdl-20233779

RESUMO

OBJECTIVES: To assess support discs, comprising polyethylene terephthalate (PET), coated with different polymer/levofloxacin combinations for antimicrobial activity in an animal model of infection, in order to explore the use of specific polymer coatings incorporating levofloxacin as a means of reducing device-related infections. METHODS: Aliphatic polyester-polyurethanes containing different ratios of poly(lactic acid) diol and poly(caprolactone) diol were prepared, blended with levofloxacin and then used to coat support discs. The in vitro levofloxacin release profiles from these discs were measured in aqueous solution. Mice were surgically implanted with the coated discs placed subcutaneously and infection was initiated by injection of 10(6) cfu of Staphylococcus aureus into the subcutaneous pocket containing the implant. After 5, 10, 20 and 30 days, the discs were removed, and the number of bacteria adhering to the implant and the residual antimicrobial activity of the discs were determined. RESULTS: In vitro, the release of levofloxacin from the coated discs occurred at a constant rate and then reached a plateau at different timepoints, depending on the polymer preparation used. In vivo, none of the discs coated with polymer blends containing levofloxacin was colonized by S. aureus, whereas 94% of the discs coated with polymer alone were infected. All discs coated with levofloxacin-blended polymers displayed residual antimicrobial activity for at least 20 days post-implantation. CONCLUSIONS: Bioerodable polyester-polyurethane polymer coatings containing levofloxacin can prevent bacterial colonization of implants in an intra-operative model of device-related infections.


Assuntos
Antibacterianos/farmacologia , Levofloxacino , Ofloxacino/farmacologia , Polímeros/farmacologia , Infecções Relacionadas à Prótese/prevenção & controle , Infecções Estafilocócicas/prevenção & controle , Animais , Contagem de Colônia Microbiana , Modelos Animais de Doenças , Feminino , Corpos Estranhos , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Staphylococcus aureus/efeitos dos fármacos
14.
Mol Microbiol ; 68(2): 314-27, 2008 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-18284589

RESUMO

Regulation of virulence gene expression plays a central role in the pathogenesis of enteric bacteria as they encounter diverse environmental conditions in the gastrointestinal tract of their hosts. In this study, we investigated environmental regulation of two putative virulence determinants adcA and kfc by RegA, an AraC/XylS-like regulator, from Citrobacter rodentium, and identified bicarbonate as the environmental signal which induced transcription of adcA and kfc through RegA. Primer extension experiments showed that adcA and kfc were divergently transcribed from sigma(70) promoters. In vivo and in vitro experiments demonstrated that bicarbonate facilitated and stabilized the binding of RegA to an operator located between the two promoters. The interaction of RegA with its DNA target resulted in the formation of a nucleosome-like structure, which evidently displaced the histone-like proteins, H-NS and StpA, from the adcA and kfc promoter regions, leading to transcriptional derepression. In addition, our results indicated that RegA also behaved as a Class I activator by directly stimulating transcription initiation by RNA polymerase. This is the first report to describe the molecular mechanism by which an environmental chemical stimulates transcription of virulence-associated genes of an enteric pathogen through an AraC/XlyS-like activator.


Assuntos
Proteínas de Bactérias/metabolismo , Bicarbonatos/metabolismo , Citrobacter rodentium/fisiologia , Regulação Bacteriana da Expressão Gênica , Óperon , Ativação Transcricional/efeitos dos fármacos , Fatores de Virulência/biossíntese , Fusão Gênica Artificial , Proteínas de Bactérias/genética , Sequência de Bases , Citrobacter rodentium/genética , Pegada de DNA , DNA Bacteriano/metabolismo , Proteínas de Ligação a DNA/metabolismo , Ensaio de Desvio de Mobilidade Eletroforética , Deleção de Genes , Genes Reporter , Dados de Sequência Molecular , Nucleossomos/metabolismo , Regiões Operadoras Genéticas , Regiões Promotoras Genéticas , Ligação Proteica , Sítio de Iniciação de Transcrição , beta-Galactosidase/genética , beta-Galactosidase/metabolismo
15.
Pharmacotherapy ; 39(4): 443-453, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30779194

RESUMO

BACKGROUND: Proton pump inhibitors (PPIs) have been linked to acute kidney injury (AKI) and chronic kidney disease (CKD); however, current evidence has only been evaluated in a small number of studies with short follow-up periods. This study examined the association between PPI use and risk of incident AKI and CKD in a large population-based health maintenance organization (HMO) cohort. METHODS: Patients aged 18 years or older, without evidence of preexisting renal disease, started on PPI therapy, and those continuously enrolled for at least 12 months between July 1993 and September 2008 were identified in an HMO database. Incidences of AKI and CKD were defined using documented International Classification of Disease, Ninth Revision, Clinical Modification (ICD-9-CM) codes or a glomerular filtration rate less than 60 ml/min/1.73 m2 after initiation of PPI therapy. Patients with AKI were followed for up to 90 days (cohort 1), and patients with CKD required at least 1 year of follow-up (cohort 2). Multivariable logistic regression analyses were used to adjust for differences in demographics (excluding race), comorbidities, and medication use between groups. RESULTS: In 93,335 patients in the AKI cohort, 16,593 of whom were exposed to PPIs, the incidence rate of AKI was higher in the PPI group than nonusers (36.4 vs 3.54 per 1000 person-years, p<0.0001, respectively). In adjusted models, PPI exposure was associated with an increased risk of AKI (adjusted odds ratio [aOR] 4.35, 95% confidence interval [CI] 3.14-6.04, p<0.0001). In 84,600 patients in the CKD cohort, 14,514 of whom were exposed to PPIs, the incidence rate of CKD was higher in the PPI group than nonusers (34.3 vs 8.75 per 1000 person-years, p<0.0001, respectively). In adjusted models, PPIs were associated with a higher risk of CKD compared with controls (aOR 1.20, 95% CI 1.12-1.28, p<0.0001). Associations between PPI use and AKI and CKD persisted in propensity score-matched analyses. CONCLUSION: The use of PPIs is associated with an increased risk of incident AKI and CKD. This relationship could have a considerable public health impact; therefore, health care provider education and deprescribing initiatives will be necessary to raise awareness and reduce health care burden.


Assuntos
Injúria Renal Aguda/induzido quimicamente , Inibidores da Bomba de Prótons/efeitos adversos , Insuficiência Renal Crônica/induzido quimicamente , Injúria Renal Aguda/epidemiologia , Adulto , Estudos de Coortes , Comorbidade , Bases de Dados Factuais , Feminino , Taxa de Filtração Glomerular , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Insuficiência Renal Crônica/epidemiologia , Estudos Retrospectivos , Fatores de Risco
16.
Infect Immun ; 76(11): 5247-56, 2008 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-18765720

RESUMO

Citrobacter rodentium is an attaching and effacing pathogen which causes transmissible colonic hyperplasia in mice. Infection with C. rodentium serves as a model for infection of humans with enteropathogenic and enterohemorrhagic Escherichia coli. To identify novel colonization factors of C. rodentium, we screened a signature-tagged mutant library of C. rodentium in mice. One noncolonizing mutant had a single transposon insertion in an open reading frame (ORF) which we designated regA because of its homology to genes encoding members of the AraC family of transcriptional regulators. Deletion of regA in C. rodentium resulted in markedly reduced colonization of the mouse intestine. Examination of lacZ transcriptional fusions using promoter regions of known and putative virulence-associated genes of C. rodentium revealed that RegA strongly stimulated transcription of two newly identified genes located close to regA, which we designated adcA and kfcC. The cloned adcA gene conferred autoaggregation and adherence to mammalian cells to E. coli strain DH5alpha, and a kfc mutation led to a reduction in the duration of intestinal colonization, but the kfc mutant was far less attenuated than the regA mutant. These results indicated that other genes of C. rodentium whose expression required activation by RegA were required for colonization. Microarray analysis revealed a number of RegA-regulated ORFs encoding proteins homologous to known colonization factors. Transcription of these putative virulence determinants was activated by RegA only in the presence of sodium bicarbonate. Taken together, these results show that RegA is a global regulator of virulence in C. rodentium which activates factors that are required for intestinal colonization.


Assuntos
Proteínas de Bactérias/genética , Citrobacter rodentium/genética , Citrobacter rodentium/patogenicidade , Infecções por Enterobacteriaceae/genética , Regulação Bacteriana da Expressão Gênica , Sequência de Aminoácidos , Animais , Aderência Bacteriana , Proteínas de Bactérias/metabolismo , Mucosa Intestinal/microbiologia , Mucosa Intestinal/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Dados de Sequência Molecular , Análise de Sequência com Séries de Oligonucleotídeos , Homologia de Sequência de Aminoácidos , Transcrição Gênica , Virulência/genética
17.
Pediatr Pulmonol ; 52(5): 632-635, 2017 05.
Artigo em Inglês | MEDLINE | ID: mdl-28328157

RESUMO

BACKGROUND: Small-colony variants (SCVs) of Staphylococcus aureus are associated with worse lung disease in children with Cystic Fibrosis (CF), exhibit a higher resistance to antibiotics and co-colonize more commonly with Pseudomonas aeruginosa compared to the normal phenotype. The prevalence of SCVs in lower airway specimens from children with CF is largely unknown. METHODS: Each visible morphotype of S. aureus was subcultured onto horse blood agar (HBA) to enable identification of SCVs. RESULTS: Sixty-one samples from 41 children (mean age 11.7 (SD 5.3) years) were identified with a positive S. aureus culture from lower respiratory tract specimens collected in 2014-2015. None of the differing morphotypes isolated were identified as S. aureus SCVs. CONCLUSION: In a center where anti staphylococcal prophylaxis is adopted, S. aureus SCVs were not isolated from the lower airways specimens in young children with CF indicating that acquisition of small colony variant S. aureus may not be a significant clinical problem in young children with CF.


Assuntos
Fibrose Cística/microbiologia , Infecções Respiratórias/microbiologia , Infecções Estafilocócicas/microbiologia , Staphylococcus aureus/isolamento & purificação , Adolescente , Antibacterianos/uso terapêutico , Criança , Fibrose Cística/complicações , Resistência Microbiana a Medicamentos , Feminino , Humanos , Masculino , Fenótipo , Pseudomonas aeruginosa/isolamento & purificação , Sistema Respiratório/microbiologia , Infecções Respiratórias/etiologia
18.
Vaccine ; 35(45): 6160-6165, 2017 10 27.
Artigo em Inglês | MEDLINE | ID: mdl-28951086

RESUMO

BACKGROUND: The 13-valent pneumococcal conjugate vaccine (PCV13) was introduced in 2010 in the U.S. and its impact on pneumococcal meningitis (PM) is unknown. We assessed the impact of PCV13 on PM hospitalization rates 4years after the vaccine was introduced. METHODS: This was a retrospective analysis of the National Inpatient Sample from 2008-2014. Patients with an ICD-9-CM code for PM (320.1) were identified and rates calculated using US Census data as the denominator. Data weights were used to derive national estimates. We examined three time periods: 2008-2009 (late post-PCV7), 2010 (transition year), and 2011-2014 (post-PCV13). RESULTS: During the study period, there were 10,493 hospitalizations due to PM in the U.S. Overall, PM incidence decreased from 0.62 to 0.38 cases per 100,000 over this time (39% decrease; P<0.01). Among children <2years, the average annualized PM rate decreased by 45% from 2.19 to 1.20 per 100,000 (P=0.10). Annual PM rates decreased in those aged 18-39years (0.25-0.15 cases per 100,000; P=0.02) and 40-64years (0.95-0.54 cases per 100,000; P=0.03). A total of 1016 deaths were due to PM, and the case fatality rate was variable over the study period (8.3%-11.2%; P=0.96). CONCLUSION: Following the introduction of PCV13, hospitalization rates for PM decreased significantly with no subsequent improvements in case-fatality rate.


Assuntos
Hospitalização/tendências , Meningite Pneumocócica/imunologia , Vacinas Pneumocócicas/imunologia , Vacinas Conjugadas/imunologia , Adolescente , Adulto , Idoso , Censos , Criança , Pré-Escolar , Feminino , Humanos , Incidência , Pacientes Internados/estatística & dados numéricos , Classificação Internacional de Doenças/estatística & dados numéricos , Masculino , Meningite Pneumocócica/prevenção & controle , Pessoa de Meia-Idade , Estudos Retrospectivos , Estados Unidos , Adulto Jovem
19.
Sci Data ; 4: 170181, 2017 12 19.
Artigo em Inglês | MEDLINE | ID: mdl-29257126

RESUMO

Technological and methodological innovations are equipping researchers with unprecedented capabilities for detecting and characterizing pathologic processes in the developing human brain. As a result, ambitions to achieve clinically useful tools to assist in the diagnosis and management of mental health and learning disorders are gaining momentum. To this end, it is critical to accrue large-scale multimodal datasets that capture a broad range of commonly encountered clinical psychopathology. The Child Mind Institute has launched the Healthy Brain Network (HBN), an ongoing initiative focused on creating and sharing a biobank of data from 10,000 New York area participants (ages 5-21). The HBN Biobank houses data about psychiatric, behavioral, cognitive, and lifestyle phenotypes, as well as multimodal brain imaging (resting and naturalistic viewing fMRI, diffusion MRI, morphometric MRI), electroencephalography, eye-tracking, voice and video recordings, genetics and actigraphy. Here, we present the rationale, design and implementation of HBN protocols. We describe the first data release (n=664) and the potential of the biobank to advance related areas (e.g., biophysical modeling, voice analysis).


Assuntos
Deficiências da Aprendizagem , Saúde Mental , Adolescente , Criança , Bases de Dados Factuais , Eletroencefalografia , Humanos , Deficiências da Aprendizagem/diagnóstico , Imagem Multimodal , Neuroimagem , Adulto Jovem
20.
ERJ Open Res ; 2(3)2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-27957481

RESUMO

Respiratory infections are a major cause of pulmonary decline in children with cystic fibrosis (CF). We compared the prevalence of infection in early life at geographically distant CF treatment centres participating in the same surveillance programme in Australia. Lower airway microbiology, inflammation and structural lung disease at annual review were evaluated for 260 children 0-8 years old with CF at 1032 visits to CF treatment centres in Melbourne or Perth. Melbourne patients were more likely to be culture-positive for common respiratory pathogens at all age groups (odds ratio (OR) 1.85, 95% CI 1.33-2.58). Subjects <2 years old in Melbourne were also more likely to have neutrophil elastase present (OR 3.11, 95% CI 1.62-5.95). Bronchiectasis (OR 2.02, 95% CI 1.21-3.38) and air trapping (OR 2.53, 95% CI 1.42-4.51) in subjects 2-5 years old was more common in Melbourne subjects. The severity of structural lung disease was also worse in Melbourne patients >5 years old. Patients at both centres had a similar rate of hospitalisations and prescribed antibiotics. No procedural differences were identified that could explain the disparity between pathogen prevalence. Geographical differences in early acquisition of infection may contribute to variability in outcomes between CF centres.

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