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Background: Historical penicillin allergy is commonly reported, but the lack of standardized allergy clinic practices may diminish the ability to delabel beta-lactam allergy appropriately. Objective: We sought to improve beta-lactam allergy testing and patient understanding of their antibiotic allergy status by standardizing testing and communication practices between 7 adult and pediatric hospital centers. Methods: Phase 1 prospectively described the beta-lactam allergy testing practices at each center. Following this, practice was standardized to achieve a defined panel of skin testing reagents, pro forma result letters for patients and referring doctors, and provision of medical alert jewelry to those with confirmed allergy. Testing outcomes and patient perception regarding allergy status 8 weeks postassessment were compared before (phase 1) and after standardization (phase 2). Primary outcomes were the percentage of participants delabeled after testing, and concordance rates between participant perception of their allergy status and their status as determined by the treating physician at 8-week follow-up. Results: Of 195 adult and pediatric participants (median age, 50 years; 21.5% <18 years; 36.9% males), 75% were delabeled of their beta-lactam allergy. No patient experienced anaphylaxis related to any beta-lactam delabeling testing. In phase 1, 75% of participants received written results, 52% were informed verbally, and 48% received results in more than 1 form. All phase 2 participants received written results (P < .01), 61% received verbal results from a physician as well (P > .05). At 8-week follow-up, 54% of phase 1 participants had concordant perceptions of their allergy status as the testing team versus 91.6% in phase2 (P < .001). Of the 17 participants who were delabeled and treated with a beta-lactam antibiotic during the 8-week follow-up period, there were no reported allergic reactions, although 1 participant experienced anaphylaxis following exposure to amoxicillin-clavulanic acid 1 year after delabeling. Conclusions: Standardization of testing and written patient information improved short-term patient perception of beta-lactam allergy status.
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BACKGROUND AND OBJECTIVES: Less than 50% of youth living with HIV know their status. The Centers for Disease Control and Prevention and the United States Preventive Services Task Force recommend universal HIV screening in adolescence. Pediatric primary care settings are still lacking in testing youth who are at risk for HIV. Our objective was to determine whether implementing rapid HIV screening improved HIV screening rates and result receipt in 13- to 25-year-old pediatric primary patients. METHODS: From March 2014 to June 2015, a 4-cycle plan-do-study-act quality improvement model was used. A total of 4433 patients aged 13 to 25 years were eligible for HIV screening on the basis of Centers for Disease Control and Prevention criteria. Logistic regression with random effects was used to estimate the odds of HIV screening and screening with a rapid test compared with each previous cycle. Statistical process control charts using standard interpretation rules assessed the effect of patients receiving rapid HIV screening. RESULTS: Baseline HIV screening rate was 29.6%; it increased to 82.7% in cycle 4. The odds of HIV screening increased 31% between cycle 1 and baseline (odds ratio 1.31 [95% confidence interval: 1.01-1.69]) to a 1272% increase between cycle 4 and baseline (odds ratio 12.72 [95% confidence interval: 10.45-15.48]), with most (90.4%) via rapid screening. Rapid screening yielded higher same-day result receipt . Five patients were identified with HIV and immediately linked to on-site care. CONCLUSIONS: Rapid HIV screening and system-level modifications significantly increased screening rates and result receipt, revealing this to be an effective method to deliver HIV services to youth.
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Infecções por HIV/diagnóstico , Programas de Rastreamento/métodos , Serviços Preventivos de Saúde/métodos , Atenção Primária à Saúde/métodos , Melhoria de Qualidade/estatística & dados numéricos , Adolescente , Adulto , Centers for Disease Control and Prevention, U.S. , Feminino , Humanos , Masculino , Programas de Rastreamento/estatística & dados numéricos , Serviços Preventivos de Saúde/estatística & dados numéricos , Atenção Primária à Saúde/estatística & dados numéricos , Estados Unidos , Serviços Urbanos de Saúde/estatística & dados numéricos , Adulto JovemRESUMO
This article presents the findings of a pre-test, post-test quality improvement project that describes the change in knowledge from prior to and following an evidence-based education presentation. The presentation addressed the clinical symptoms, diagnostic processes, interventions, and responsibilities of licensed and unlicensed health care workers employed in long-term care facilities related to prevention and detection of non-catheter-related urinary tract infections. Results indicate that the education presentation improved knowledge in specific.
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Conhecimentos, Atitudes e Prática em Saúde , Assistência de Longa Duração , Enfermagem em Nefrologia/educação , Infecções Urinárias/enfermagem , Enfermagem Baseada em Evidências , Humanos , Licenciamento em Enfermagem , Melhoria de Qualidade , Inquéritos e Questionários , Infecções Urinárias/diagnóstico , Infecções Urinárias/prevenção & controleRESUMO
UNLABELLED: Bacteria engage in chemical signaling, termed quorum sensing (QS), to mediate intercellular communication, mimicking multicellular organisms. The LuxR family of QS transcription factors regulates gene expression, coordinating population behavior by sensing endogenous acyl homoserine lactones (AHLs). However, some bacteria (such as Escherichia coli) do not produce AHLs. These LuxR orphans sense exogenous AHLs but also regulate transcription in the absence of AHLs. Importantly, this AHL-independent regulatory mechanism is still largely unknown. Here we present several structures of one such orphan LuxR-type protein, SdiA, from enterohemorrhagic E. coli (EHEC), in the presence and absence of AHL. SdiA is actually not in an apo state without AHL but is regulated by a previously unknown endogenous ligand, 1-octanoyl-rac-glycerol (OCL), which is ubiquitously found throughout the tree of life and serves as an energy source, signaling molecule, and substrate for membrane biogenesis. While exogenous AHL renders to SdiA higher stability and DNA binding affinity, OCL may function as a chemical chaperone placeholder that stabilizes SdiA, allowing for basal activity. Structural comparison between SdiA-AHL and SdiA-OCL complexes provides crucial mechanistic insights into the ligand regulation of AHL-dependent and -independent function of LuxR-type proteins. Importantly, in addition to its contribution to basic science, this work has implications for public health, inasmuch as the SdiA signaling system aids the deadly human pathogen EHEC to adapt to a commensal lifestyle in the gastrointestinal (GI) tract of cattle, its main reservoir. These studies open exciting and novel avenues to control shedding of this human pathogen in the environment. IMPORTANCE: Quorum sensing refers to bacterial chemical signaling. The QS acyl homoserine lactone (AHL) signals are recognized by LuxR-type receptors that regulate gene transcription. However, some bacteria have orphan LuxR-type receptors and do not produce AHLs, sensing them from other bacteria. We solved three structures of the E. coli SdiA orphan, in the presence and absence of AHL. SdiA with no AHL is not in an apo state but is regulated by a previously unknown endogenous ligand, 1-octanoyl-rac-glycerol (OCL). OCL is ubiquitously found in prokaryotes and eukaryotes and is a phospholipid precursor for membrane biogenesis and a signaling molecule. While AHL renders to SdiA higher stability and DNA-binding affinity, OCL functions as a chemical chaperone placeholder, stabilizing SdiA and allowing for basal activity. Our studies provide crucial mechanistic insights into the ligand regulation of SdiA activity.
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Acil-Butirolactonas/metabolismo , Diglicerídeos/metabolismo , Escherichia coli Êntero-Hemorrágica/efeitos dos fármacos , Proteínas de Escherichia coli/metabolismo , Regulação Bacteriana da Expressão Gênica/efeitos dos fármacos , Percepção de Quorum , Transativadores/metabolismo , Transcrição Gênica/efeitos dos fármacos , Acil-Butirolactonas/química , Animais , Bovinos , Cristalografia por Raios X , Diglicerídeos/química , Escherichia coli Êntero-Hemorrágica/genética , Escherichia coli Êntero-Hemorrágica/fisiologia , Proteínas de Escherichia coli/química , Humanos , Modelos Moleculares , Conformação Proteica , Estabilidade Proteica , Transativadores/químicaRESUMO
Hypoxia inducible factors (HIFs) are heterodimeric transcription factors induced in a variety of pathophysiological settings, including cancer. We describe the first detailed structure-activity relationship study of small molecules designed to inhibit HIF-2α-ARNT heterodimerization by binding an internal cavity of the HIF-2α PAS-B domain. Through a series of biophysical characterizations of inhibitor-protein interactions (NMR and X-ray crystallography), we have established the structural requirements for artificial inhibitors of the HIF-2α-ARNT PAS-B interaction. These results may serve as a foundation for discovering therapeutic agents that function by a novel mode of action.
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Fatores de Transcrição Hélice-Alça-Hélice Básicos/antagonistas & inibidores , Translocador Nuclear Receptor Aril Hidrocarboneto/química , Fatores de Transcrição Hélice-Alça-Hélice Básicos/química , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Cristalografia por Raios X , Ensaios de Triagem em Larga Escala , Humanos , Espectroscopia de Ressonância Magnética , Modelos Moleculares , Estrutura Molecular , Mutação , Oxidiazóis/síntese química , Oxidiazóis/química , Ligação Proteica , Multimerização Proteica , Estrutura Terciária de Proteína , Bibliotecas de Moléculas Pequenas/química , Relação Estrutura-AtividadeRESUMO
Biocatalysis has become an important method in the pharmaceutical industry for the incorporation of new functionality in small molecules. Currently this method is limited in the types of reactions that can be carried out and no strategy exists to systematically screen for new biocatalyzed reactions. This study involves the development of a medium throughput screen to identify and optimize new reactions using a series of marine-derived bacterial cell lines, which were screened against several (13)C labeled organic substrates. The reactions were analyzed using (13)C NMR as the primary screening tool. We describe the discovery of a bacterial catalyzed indole oxidation reaction in which complete conversion of (13)C labeled N-methyl indole to 3-hydroxyindole was observed. In addition, the sensitivity of this reaction to dO(2) levels can be exploited to oxidize to either 3-hydroxyindole or 2-oxoindole. This new platform sets up an important tool for the discovery of new organic transformations using an extensive library of marine bacteria.
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Actinobacteria/enzimologia , Indóis/metabolismo , Actinobacteria/química , Actinobacteria/metabolismo , Biocatálise , Biotransformação , Isótopos de Carbono/análise , Isótopos de Carbono/metabolismo , Indóis/química , Oxirredução , Oxigênio/metabolismoRESUMO
The principles of autonomy, beneficence, non-maleficence, and justice are well established ethical principles in health research. Of these principles, justice has received less attention by health researchers. The purpose of this article is to broaden the discussion of health research ethics, particularly the ethical principle of justice, to include societal considerations--who and what are studied and why?--and to critique current applications of ethical principles within this broader view. We will use a feminist intersectional approach in the context of health disparities research to firmly establish inseparable links between health research ethics, social action, and social justice. The aim is to provide an ethical approach to health disparities research that simultaneously describes and seeks to eliminate health disparities.
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Temas Bioéticos , Feminismo , Pesquisa sobre Serviços de Saúde/ética , Disparidades em Assistência à Saúde , Justiça Social , Feminino , Disparidades em Assistência à Saúde/ética , Humanos , MasculinoRESUMO
OBJECTIVE: To describe a pilot programme that consisted of identifying, contacting and providing HIV testing to members of social and sexual networks of HIV-infected youth patients as a part of routine clinical care at an adolescent HIV clinic in Baltimore, Maryland, USA. METHODS: Forty-nine sexually active HIV-infected adolescent patients were interviewed about their social and sexual contacts at a routine HIV clinic visit. A trained community health worker located these referred social and sexual contacts, and encouraged them to make an appointment for HIV counselling, testing and referral (CTR) services. RESULTS: During a period of 18 months, 26 index youths provided locating information on 53 first-generation contacts and these 53 contacts provided information on 16 second-generation contacts. A total of 32 contacts received counselling services and 25 were tested for HIV infection, yielding three new HIV-positive individuals. CONCLUSION: As a part of standard care for regular visits of HIV-infected youth patients, interviewing about their social and sexual contacts could be a viable strategy in identifying high-risk youths for HIV infection and subsequent CTR services.
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Infecções por HIV/psicologia , Apoio Social , Adolescente , Adulto , Baltimore , Preservativos/estatística & dados numéricos , Aconselhamento , Revelação , Feminino , Educação em Saúde , Humanos , Entrevistas como Assunto , Masculino , Projetos Piloto , Fatores de Risco , Comportamento de Redução do Risco , Parceiros Sexuais , Sexo sem Proteção/psicologia , Sexo sem Proteção/estatística & dados numéricos , Adulto JovemRESUMO
Seventy-one of 84 human immunodeficiency virus (HIV)-infected children [84.5% (95% confidence interval: 75-91.5%)] were hepatitis A virus (HAV) seropositive after 2 doses of HAV vaccine. Higher CD4% and HIV suppression were significantly associated with increased HAV seropositivity rate. In multivariate analysis, CD4 >or=25% and young age were independent predictors of HAV seropositivity. Of 7 children given a third HAV vaccine dose because of negative HAV antibody after 2 doses, 2 (29%) became seropositive.