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1.
Lancet Reg Health Southeast Asia ; 15: 100239, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37614357

RESUMO

Background: Women are estimated to hold between 70 and 75% of global health positions worldwide yet persistent inequities in power and leadership remain. There is little information on specific enablers and barriers that women working in public health face in India and how those compare with other regions. Methods: We collected and analyzed information from women working in public health in India and East Africa (Kenya, Rwanda, and Uganda) and in global health (Canada and United States), to understand and document the specific enablers and barriers women face in India, compared with other regions. Findings: Several universal themes emerged around factors enabling (mentors, professional networks, leadership based in empathy and team building) or impeding (obvert bias and family responsibilities) women across all contexts. Within this, there are nuances in how women's leadership growth factors and obstacles play out in India differently than in other contexts. Interpretation: There are important similarities in the enablers and barriers faced by women in India and other geographies and important ways these differs in for women in India. By designing programs and policies at institutional levels to address these factors, we can create a professional ecosystem that works for women in health and beyond. Funding: This research was funded by WomenLift Health, which is funded by the Bill and Melinda Gates Foundation. Representatives from WomenLift Health, listed as authors, participated in the conceptualization of the research to define objectives and core questions, provided commentary and revision to improve the manuscript, and supervised the progress of the research.

2.
ACS Omega ; 7(19): 16584-16592, 2022 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-35601290

RESUMO

The ongoing public health emergency of opioid use disorders (OUD) and overdose in the United States is largely driven by fentanyl and its related analogues and has resulted in over 75 673 deaths in 2021. Immunotherapeutics such as vaccines have been investigated as a potential interventional strategy complementary to current pharmacotherapies to reduce the incidence of OUD and opioid-related overdose. Given the importance of targeting structurally distinct fentanyl analogues, this study compared a previously established lead conjugate vaccine (F1-CRM) to a series of novel vaccines incorporating haptens derived from alfentanil and acetylfentanyl (F8, 9a, 9b, 10), and evaluated their efficacy against drug-induced pharmacological effects in rats. While no vaccine tested provided significant protection against alfentanil, lead formulations were effective in reducing antinociception, respiratory depression, and bradycardia elicited by fentanyl, sufentanil, and acetylfentanyl. Compared with control, vaccination with F1-CRM also reduced drug levels in the brain of rats challenged with lethal doses of fentanyl. These data further support investigation of F1-CRM as a candidate vaccine against fentanyl and selected analogues.

3.
Educ Stud Math ; 108(3): 513-532, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34934232

RESUMO

The emergence of the COVID-19 pandemic has brought increased attention to the critical mathematical literacy of citizens in the United States and around the world. A statistically and mathematically literate society is crucial for ensuring that citizens are able to sift through political rhetoric to maintain life-saving procedures such as social distancing and other infection dampening efforts. Additionally, recent civil unrest due to the disproportionate killings of Black men by police provokes investigation into the public's mathematical literacy. In this paper, we investigate adolescent students' critical mathematics consciousness and mathematics literacy as they reason through two interview tasks on the coronavirus and police shooting data. Drawing on Frankenstein's program of Critical Mathematics Education, we introduce an analytic framework for documenting the critical mathematics consciousness of adolescent students. We interviewed fifteen 14- to 16-year-old students as they solved five tasks designed to elicit their critical and ethical mathematical awareness. Our findings indicate that students exhibit very little critical mathematics consciousness in the context of the police problem but show awareness that data can be presented in ways that manipulate the public's emotions in the coronavirus problem. We conclude the paper with a discussion of implications for designing future instruction to support students' growth in critical mathematics consciousness.

4.
Hum Vaccin Immunother ; 17(11): 4383-4392, 2021 11 02.
Artigo em Inglês | MEDLINE | ID: mdl-34411500

RESUMO

Vaccines offer a promising prophylactic and therapeutic intervention to counteract opioid use disorders (OUD) and fatal overdoses. Vaccines generate opioid-specific antibodies that bind the target opioid, reducing drug distribution to the brain and preventing drug-induced behavioral and pharmacological effects. Due to their selectivity, anti-opioid vaccines can be administered in combination with FDA-approved medications. Because patients with OUD or other substance use disorders may be affected by other multifactorial co-morbidities, such as infection or depression, it is important to test whether vaccine efficacy is modified by factors that may impact individual innate or adaptive immunity. To that end, this study tested whether housing conditions would affect the efficacy of two lead vaccine formulations targeting oxycodone and fentanyl in male mice and rats, and further analyzed whether differences in the gastrointestinal (GI) microbiome would be correlated with either vaccine efficacy or housing conditions. Results showed that housing mice and rats in either conventional (non-controlled) or specific pathogen-free (SPF, sterile barrier maintained) environment did not affect vaccine-induced antibody responses against oxycodone and fentanyl, nor their efficacy against oxycodone- and fentanyl-induced antinociception, respiratory depression, and bradycardia. Differences in the GI microbiome detected via 16S rRNA gene sequencing were related to the housing environment. This study supports use of anti-opioid vaccines in clinical populations that may display deficits in microbiome function.


Assuntos
Transtornos Relacionados ao Uso de Opioides , Vacinas , Animais , Qualidade Habitacional , Humanos , Masculino , Camundongos , RNA Ribossômico 16S , Ratos , Eficácia de Vacinas
5.
J Alzheimers Dis ; 80(2): 831-840, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33554913

RESUMO

BACKGROUND: Neuroimaging markers provide quantitative insight into brain structure and function in neurodegenerative diseases, such as Alzheimer's disease, where we lack mechanistic insights to explain pathophysiology. These mechanisms are often mediated by genes and genetic variations and are often studied through the lens of genome-wide association studies. Linking these two disparate layers (i.e., imaging and genetic variation) through causal relationships between biological entities involved in the disease's etiology would pave the way to large-scale mechanistic reasoning and interpretation. OBJECTIVE: We explore how genetic variants may lead to functional alterations of intermediate molecular traits, which can further impact neuroimaging hallmarks over a series of biological processes across multiple scales. METHODS: We present an approach in which knowledge pertaining to single nucleotide polymorphisms and imaging readouts is extracted from the literature, encoded in Biological Expression Language, and used in a novel workflow to assist in the functional interpretation of SNPs in a clinical context. RESULTS: We demonstrate our approach in a case scenario which proposes KANSL1 as a candidate gene that accounts for the clinically reported correlation between the incidence of the genetic variants and hippocampal atrophy. We find that the workflow prioritizes multiple mechanisms reported in the literature through which KANSL1 may have an impact on hippocampal atrophy such as through the dysregulation of cell proliferation, synaptic plasticity, and metabolic processes. CONCLUSION: We have presented an approach that enables pinpointing relevant genetic variants as well as investigating their functional role in biological processes spanning across several, diverse biological scales.


Assuntos
Doença de Alzheimer/genética , Predisposição Genética para Doença/genética , Neuroimagem , Biologia de Sistemas , Doença de Alzheimer/diagnóstico por imagem , Biomarcadores/metabolismo , Encéfalo/metabolismo , Encéfalo/patologia , Estudo de Associação Genômica Ampla/métodos , Humanos , Fenótipo , Polimorfismo de Nucleotídeo Único/genética , Biologia de Sistemas/métodos
6.
J Pediatr Pharmacol Ther ; 26(2): 172-178, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33603581

RESUMO

OBJECTIVE: The administration of hyperosmolar oral products in neonates has been associated with gastrointestinal complications. The American Academy of Pediatrics recommends a maximum osmolality of 450 mOsm/kg for formulas and enteral nutrition for term infants, and recent studies reported intolerance to enteral nutrition with osmolality above 500 mOsm/kg in low birthweight infants. The osmolality of medications administered to neonates is often not available in the literature or from manufacturers. The purpose of this study was to determine the osmolality of oral medications commonly administered to neonates in the NICU. METHODS: Fifty-two oral medications were chosen for this study, including solutions, suspensions, syrups, elixirs, and intravenous solutions administered orally. The osmolality of each medication was measured in triplicate by using freezing point depression. RESULTS: Thirty-seven of the 43 medications with measurable values (86.1%) had an osmolality greater than 500 mOsm/kg, and 6 medications (14%) had an osmolality less than 500 mOsm/kg. Nine medications did not result in a value. CONCLUSIONS: Our study provides osmolality data on oral medications commonly used in neonates with most oral medications having an osmolality greater than 500 mOsm/kg.

7.
J Patient Saf ; 17(1): e10-e14, 2021 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-32168273

RESUMO

OBJECTIVES: Medications often require manipulations to measure and administer the correct dose for pediatric patients. These manipulations pose medication safety risks. The objective of this study was to determine the frequency of drug formulation manipulations in the pediatric inpatient population and compare the findings to a parallel adult inpatient population. METHODS: Observations were conducted at four sites with 1 day of data collection per week by a randomized schedule for 5 weeks. All pediatric inpatients at each study site were included as well as an equivalent number of medication orders from adult inpatients with similar levels of care. The percentage of medication orders requiring a manipulation were evaluated and compared between pediatric and adult patients. RESULTS: A total of 15,722 medication orders were analyzed. Drug formulation manipulation was required in 3925 (49.9%) of 7861 pediatric orders versus 1301 of 7861 adult orders (16.6%) (P < 0.05). By pediatric service, drug manipulations were required most frequently (71.5% of orders) in the neonatal intensive care unit. The most common dosage forms requiring manipulation for pediatric patients were oral liquids (45.7% of orders) and intravenous medications (44.6% of orders). By pediatric patient age, drug manipulation was required most often in patients aged 1 to 12 months (69.8% of orders). CONCLUSIONS: Drug formulation manipulation was three times more common in pediatric inpatient practice compared with adult inpatient practice in this study. This study demonstrated a statistically significant difference in the prevalence of drug formulation manipulation between pediatric and adult inpatients.


Assuntos
Composição de Medicamentos/métodos , Pacientes Internados/estatística & dados numéricos , Adolescente , Adulto , Criança , Pré-Escolar , Coleta de Dados , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Adulto Jovem
8.
J Med Chem ; 63(23): 14647-14667, 2020 12 10.
Artigo em Inglês | MEDLINE | ID: mdl-33215913

RESUMO

The incidence of fatal overdoses has increased worldwide due to the widespread access to illicit fentanyl and its potent analogues. Vaccines offer a promising strategy to reduce the prevalence of opioid use disorders (OUDs) and to prevent toxicity from accidental and deliberate exposure to fentanyl and its derivatives. This study describes the development and characterization of vaccine formulations consisting of novel fentanyl-based haptens conjugated to carrier proteins. Vaccine efficacy was tested against opioid-induced behavior and toxicity in mice and rats challenged with fentanyl and its analogues. Prophylactic vaccination reduced fentanyl- and sufentanil-induced antinociception, respiratory depression, and bradycardia in mice and rats. Therapeutic vaccination also reduced fentanyl intravenous self-administration in rats. Because of their selectivity, vaccines did not interfere with the pharmacological effects of commonly used anesthetics nor with methadone, naloxone, oxycodone, or heroin. These preclinical data support the translation of vaccines as a viable strategy to counteract fentanyl use disorders and toxicity.


Assuntos
Fentanila/imunologia , Transtornos Relacionados ao Uso de Opioides/prevenção & controle , Transtornos Relacionados ao Uso de Opioides/terapia , Vacinas/imunologia , Animais , Proteínas de Bactérias/química , Proteínas de Bactérias/imunologia , Bovinos , Toxina Diftérica/química , Toxina Diftérica/imunologia , Feminino , Haptenos/química , Haptenos/imunologia , Hemocianinas/química , Hemocianinas/imunologia , Masculino , Camundongos Endogâmicos BALB C , Piperidinas/síntese química , Piperidinas/imunologia , Estudo de Prova de Conceito , Ratos Sprague-Dawley , Soroalbumina Bovina/química , Soroalbumina Bovina/imunologia , Sufentanil/imunologia
9.
NPJ Vaccines ; 5: 99, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33101712

RESUMO

Opioid use disorders (OUD) affect over 27 million people worldwide. Anti-opioid vaccines offer a promising strategy to treat OUD and prevent overdose. Using immunomodulation of cytokine signaling to increase vaccine efficacy, this study found that blocking IL-4 improved the efficacy of vaccines targeting oxycodone and fentanyl in male and female mice. Genetic deletion of the IL-4 receptor, STAT6, or antibody-based depletion of IL-13, did not increase vaccine efficacy against opioids, suggesting the involvement of type I IL-4 receptors. Enhancement of vaccine efficacy with blockade of IL-4 was associated with improved germinal center formation in secondary lymphoid organs and selective transcriptome signatures in the activated CD4+ T cell population subset. These data suggest that IL-4 is both a pharmacological target and a potential biomarker of vaccine efficacy against OUD.

10.
J Obstet Gynaecol Can ; 42(10): 1217-1222, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32694071

RESUMO

OBJECTIVES: To describe the response rate to chemotherapy, rates of recurrence, and overall survival in patients with non-serous epithelial ovarian cancers. METHODS: This retrospective cohort study used the Manitoba Cancer Registry to identify all women with non-serous epithelial ovarian, fallopian, or peritoneal cancer treated between 1995 and 2010. Chart review entailed extracting information regarding therapy and outcomes. All patients with recurrence were identified and response to chemotherapy was assessed. RESULTS: We identified 392 patients with non-serous ovarian cancers, 192 of whom received chemotherapy in the first-line setting. Optimal debulking resulted in improvements in rates of recurrence and overall survival (P < 0.001). Histology did not have an effect on recurrence or overall survival. Forty-eight patients (25%) had a recurrence and received second-line therapy, and 21 (11%) received third-line therapy. Response rates were similar regardless of histology. In the second-line setting, 40.9%-83.3% of patients (other > mucinous > clear cell > endometrioid) and in the third-line setting, 33.3%-75.0% of patients (other > mucinous > clear cell > endometrioid) received >6 lines of chemotherapy. Twenty-three percent of patients experienced a recurrence within 2 years of first-line therapy. Two-year survival was 79.4% after first-line treatment, 27.6% after second-line treatment, and 19.5% after third-line treatment. CONCLUSION: Patients with clear cell ovarian cancer had chemotherapy continuation rates similar to those of previously reported studies. This is one of the first studies reporting response rates for mucinous and endometrioid subtypes. Recurrent disease responds to treatment with second- and third-line therapy, emphasizing the importance of offering patients subsequent lines of chemotherapy for disease management. Further studies are needed to determine the optimal regimen.


Assuntos
Antineoplásicos/uso terapêutico , Carcinoma Epitelial do Ovário/tratamento farmacológico , Neoplasias Ovarianas/tratamento farmacológico , Adulto , Idoso , Feminino , Humanos , Manitoba/epidemiologia , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/epidemiologia , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Neoplasias Ovarianas/patologia , Estudos Retrospectivos , Resultado do Tratamento
11.
J Clin Virol ; 124: 104262, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32007841

RESUMO

BACKGROUND: In 2014, enterovirus D68 (EV-D68) was responsible for an outbreak of severe respiratory illness in children, with 1,153 EV-D68 cases reported across 49 states. Despite this, there is no commercial assay for its detection in routine clinical care. BioFire® Syndromic Trends (Trend) is an epidemiological network that collects, in near real-time, deidentified. BioFire test results worldwide, including data from the BioFire® Respiratory Panel (RP). OBJECTIVES: Using the RP version 1.7 (which was not explicitly designed to differentiate EV-D68 from other picornaviruses), we formulate a model, Pathogen Extended Resolution (PER), to distinguish EV-D68 from other human rhinoviruses/enteroviruses (RV/EV) tested for in the panel. Using PER in conjunction with Trend, we survey for historical evidence of EVD68 positivity and demonstrate a method for prospective real-time outbreak monitoring within the network. STUDY DESIGN: PER incorporates real-time polymerase chain reaction metrics from the RPRV/EV assays. Six institutions in the United States and Europe contributed to the model creation, providing data from 1,619 samples spanning two years, confirmed by EV-D68 gold-standard molecular methods. We estimate outbreak periods by applying PER to over 600,000 historical Trend RP tests since 2014. Additionally, we used PER as a prospective monitoring tool during the 2018 outbreak. RESULTS: The final PER algorithm demonstrated an overall sensitivity and specificity of 87.1% and 86.1%, respectively, among the gold-standard dataset. During the 2018 outbreak monitoring period, PER alerted the research network of EV-D68 emergence in July. One of the first sites to experience a significant increase, Nationwide Children's Hospital, confirmed the outbreak and implemented EV-D68 testing at the institution in response. Applying PER to the historical Trend dataset to determine rates among RP tests, we find three potential outbreaks with predicted regional EV-D68 rates as high as 37% in 2014, 16% in 2016, and 29% in 2018. CONCLUSIONS: Using PER within the Trend network was shown to both accurately predict outbreaks of EV-D68 and to provide timely notifications of its circulation to participating clinical laboratories.


Assuntos
Surtos de Doenças , Enterovirus Humano D , Infecções por Enterovirus/diagnóstico , Infecções por Enterovirus/epidemiologia , Infecções Respiratórias/diagnóstico , Infecções Respiratórias/epidemiologia , Algoritmos , Criança , Infecções por Enterovirus/virologia , Monitoramento Epidemiológico , Europa (Continente)/epidemiologia , Humanos , Infecções Respiratórias/virologia , Sensibilidade e Especificidade , Estados Unidos/epidemiologia
12.
Stat Med ; 39(8): 1145-1155, 2020 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-31985869

RESUMO

Estimation of epidemic onset timing is an important component of controlling the spread of seasonal infectious diseases within community healthcare sites. The Above Local Elevated Respiratory Illness Threshold (ALERT) algorithm uses a threshold-based approach to suggest incidence levels that historically have indicated the transition from endemic to epidemic activity. In this paper, we present the first detailed overview of the computational approach underlying the algorithm. In the motivating example section, we evaluate the performance of ALERT in determining the onset of increased respiratory virus incidence using laboratory testing data from the Children's Hospital of Colorado. At a threshold of 10 cases per week, ALERT-selected intervention periods performed better than the observed hospital site periods (2004/2005-2012/2013) and a CUSUM method. Additional simulation studies show how data properties may effect ALERT performance on novel data. We found that the conditions under which ALERT showed ideal performance generally included high seasonality and low off-season incidence.


Assuntos
Doenças Transmissíveis , Influenza Humana , Algoritmos , Colorado/epidemiologia , Doenças Transmissíveis/epidemiologia , Surtos de Doenças , Humanos , Influenza Humana/epidemiologia , Vigilância da População , Estações do Ano
13.
Am J Trop Med Hyg ; 101(3): 534-540, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31392942

RESUMO

Multiplex polymerase chain reaction (PCR) platforms have enhanced understanding of intestinal pathogens in low- and middle-income countries (LMICs). However, few such studies have been performed in Latin America, where poverty, poor sanitation, and undernutrition persist. Multiplex PCR (BioFire, Salt Lake City, UT) was used to identify viral, bacterial, and parasitic pathogens in stool collected on day 1 and 31 from children aged 6 to 35 months with acute, non-bloody diarrhea in two locations (rural and urban) in Guatemala. We analyzed correlation between pathogens and clinical, demographic, and socioeconomic variables; described patterns of pathogen acquisition, persistence, and clearance over the 30-day period; and calculated population attributable fractions (PAFs) for diarrheal causation for individual pathogens. We analyzed 316 subjects (144 urban; 172 rural) enrolled between March 2015 and January 2016. Rural subjects had significantly more malnutrition, animal exposure, and unimproved water/sanitation infrastructure. The majority of subjects had multiple pathogens/sample (4.8 rural and 2.7 urban). Few meaningful correlates were identified between individual pathogens and clinical, demographic, or environmental variables. Escherichia coli pathotypes, Shigella, Campylobacter, and Giardia had high rates of persistence between initial and 30-day follow-up. Statistically significant adjusted PAFs were identified for Campylobacter (14.9%, 95% CI: 3.2-23.1), norovirus (10.2%, 95% CI: 0.4-17.1), sapovirus (7.6%, 95% CI: 2.3-10.9), and adenovirus 40/41 (5.6%, 95% CI: 0.3-8.7). These observations further characterize the diversity and complexity of enteric pathogens in children in LMICs. Patterns of chronic symptomatic and asymptomatic infection among Latin American children are similar to those observed in other LMIC regions. Findings have direct implications for practitioners treating individuals with acute infectious diarrhea and should inform regional public health strategies.


Assuntos
Diarreia/diagnóstico , Reação em Cadeia da Polimerase Multiplex , População Rural , População Urbana , Doença Aguda , Animais , Bactérias/genética , Bactérias/patogenicidade , Pré-Escolar , Coinfecção/diagnóstico , Coinfecção/microbiologia , Coinfecção/parasitologia , Coinfecção/virologia , Diarreia/microbiologia , Diarreia/parasitologia , Diarreia/virologia , Feminino , Trato Gastrointestinal/microbiologia , Trato Gastrointestinal/parasitologia , Trato Gastrointestinal/virologia , Humanos , Lactente , Masculino , Parasitos/genética , Parasitos/patogenicidade , Vírus/genética , Vírus/patogenicidade
14.
BMJ Case Rep ; 12(6)2019 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-31248894

RESUMO

Human parechovirus-3 (PeVA3) infection is a common cause of febrile illness in young infants and the spectrum of clinical presentation is broad. We describe a term infant who presented with marked abdominal distension and anorexia, concerning for an acute surgical abdomen. Evaluation revealed that the infant had PeVA3 infection. This case highlights the importance of recognising severe abdominal distension and discomfort as a clinical presentation associated with PeV and the potential utility of rapid testing for PeV.


Assuntos
Abdome/patologia , Abdome/virologia , Parechovirus/isolamento & purificação , Infecções por Picornaviridae/diagnóstico , Infecções por Picornaviridae/patologia , Diagnóstico Diferencial , Humanos , Recém-Nascido , Masculino
15.
Hum Vaccin Immunother ; 15(4): 909-917, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30625019

RESUMO

Opioid use disorders (OUD) and fatal overdoses are a national emergency in the United States. Therapeutic vaccines offer a promising strategy to treat OUD and reduce the incidence of overdose. Immunization with opioid-based haptens conjugated to immunogenic carriers elicits opioid-specific antibodies that block opioid distribution to the brain and reduce opioid-induced behavior and toxicity in pre-clinical models. This study tested whether the efficacy of a lead oxycodone conjugate vaccine was improved by formulation in either aluminum hydroxide or the squalene-based oil-in-water emulsion MF59 adjuvant, which was recently FDA-approved for influenza vaccines in subjects 65+ years old. In adult BALB/c mice, alum formulation was more effective than MF59 at promoting the early expansion of hapten-specific B cells and the production of oxycodone-specific serum IgG antibodies, as well as blocking oxycodone distribution to the brain and oxycodone-induced motor activity. Alum was also more effective than MF59 at promoting early differentiation of peptide-specific MHCII-restricted CD4+ Tfh and GC-Tfh cells in adult C57Bl/6 mice immunized with a model peptide-protein conjugate. In contrast, alum and MF59 were equally effective in promoting hapten-specific B cells and peptide-specific MHCII-restricted CD4+ T cell differentiation in older C57Bl/6 mice. These data suggest that alum is a more effective adjuvant than MF59 for conjugate vaccines targeting synthetic small molecule haptens or peptide antigens in adult, but not aged, mice.


Assuntos
Adjuvantes Imunológicos/administração & dosagem , Compostos de Alúmen/administração & dosagem , Centro Germinativo/efeitos dos fármacos , Transtornos Relacionados ao Uso de Opioides/imunologia , Transtornos Relacionados ao Uso de Opioides/terapia , Polissorbatos/administração & dosagem , Esqualeno/administração & dosagem , Adjuvantes Imunológicos/química , Compostos de Alúmen/química , Animais , Linfócitos B/imunologia , Overdose de Drogas , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Oxicodona/química , Oxicodona/imunologia , Peptídeos/química , Peptídeos/imunologia , Polissorbatos/química , Proteínas/química , Proteínas/imunologia , Esqualeno/química , Vacinas Conjugadas/administração & dosagem , Vacinas Conjugadas/imunologia
16.
J Microbiol Methods ; 156: 60-67, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30527965

RESUMO

BACKGROUND: Pathogen detection in pediatric patients with musculoskeletal infections relies on conventional bacterial culture, which is slow and can delay antimicrobial optimization. The ability to rapidly identify causative agents and antimicrobial resistance genes in these infections may improve clinical care. METHODS: Convenience specimens from bone and joint samples submitted for culture to Children's Hospital Colorado (CHCO) from June 2012 to October 2016 were evaluated using a "Musculoskeletal Diagnostic Panel" (MDP) consisting of the Xpert MRSA/SA SSTI real-time PCR (qPCR, Cepheid) and laboratory-developed qPCRs for Kingella kingae detection and erm genes A, B, and C which confer clindamycin resistance. Results from the MDP were compared to culture and antimicrobial susceptibility testing (AST) results. RESULTS: A total of 184 source specimens from 125 patients were tested. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the Xpert MRSA/SA SSTI compared to culture and AST results were 85%, 98%, 93%, and 95% respectively for MSSA and 82%, 100%, 100%, and 99% for MRSA. Compared to phenotypic clindamycin resistance in S. aureus isolates, the erm A, B, and C gene PCRs collectively demonstrated a sensitivity, specificity, PPV, and NPV of 80%, 96%, 67%, and 98%. In comparison to clinical truth, Kingella PCR had a sensitivity, specificity, PPV, and NPV of 100%, 99.5%, 100%, and 100%. CONCLUSIONS: This novel MDP offers a rapid, sensitive, and specific option for pathogen detection in pediatric patients with musculoskeletal infections.


Assuntos
Farmacorresistência Bacteriana , Kingella kingae/isolamento & purificação , Infecções por Neisseriaceae/diagnóstico , Osteoartrite/microbiologia , Osteomielite/microbiologia , Antibacterianos/uso terapêutico , Proteínas de Bactérias/genética , Criança , Clindamicina/uso terapêutico , Feminino , Humanos , Kingella kingae/genética , Masculino , Metiltransferases/genética
17.
Front Mol Biosci ; 6: 158, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31993440

RESUMO

Dementia-related diseases like Alzheimer's Disease (AD) have a tremendous social and economic cost. A deeper understanding of its underlying pathophysiologies may provide an opportunity for earlier detection and therapeutic intervention. Previous approaches for characterizing AD were targeted at single aspects of the disease. Yet, due to the complex nature of AD, the success of these approaches was limited. However, in recent years, advancements in integrative disease modeling, built on a wide range of AD biomarkers, have taken a global view on the disease, facilitating more comprehensive analysis and interpretation. Integrative AD models can be sorted in two primary types, namely hypothetical models and data-driven models. The latter group split into two subgroups: (i) Models that use traditional statistical methods such as linear models, (ii) Models that take advantage of more advanced artificial intelligence approaches such as machine learning. While many integrative AD models have been published over the last decade, their impact on clinical practice is limited. There exist major challenges in the course of integrative AD modeling, namely data missingness and censoring, imprecise human-involved priori knowledge, model reproducibility, dataset interoperability, dataset integration, and model interpretability. In this review, we highlight recent advancements and future possibilities of integrative modeling in the field of AD research, showcase and discuss the limitations and challenges involved, and finally, propose avenues to address several of these challenges.

18.
Future Microbiol ; 13: 1553-1554, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30421966

RESUMO

In Response to: Duff S, et al. "Economic analysis of rapid multiplex polymerase chain reaction testing for meningitis/encephalitis in pediatric patients" Future Microbiology (2018) (Epub ahead of print).


Assuntos
Meningite , Reação em Cadeia da Polimerase Multiplex , Criança , Encefalite , Humanos
19.
JMIR Public Health Surveill ; 4(3): e59, 2018 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-29980501

RESUMO

BACKGROUND: Health care and public health professionals rely on accurate, real-time monitoring of infectious diseases for outbreak preparedness and response. Early detection of outbreaks is improved by systems that are comprehensive and specific with respect to the pathogen but are rapid in reporting the data. It has proven difficult to implement these requirements on a large scale while maintaining patient privacy. OBJECTIVE: The aim of this study was to demonstrate the automated export, aggregation, and analysis of infectious disease diagnostic test results from clinical laboratories across the United States in a manner that protects patient confidentiality. We hypothesized that such a system could aid in monitoring the seasonal occurrence of respiratory pathogens and may have advantages with regard to scope and ease of reporting compared with existing surveillance systems. METHODS: We describe a system, BioFire Syndromic Trends, for rapid disease reporting that is syndrome-based but pathogen-specific. Deidentified patient test results from the BioFire FilmArray multiplex molecular diagnostic system are sent directly to a cloud database. Summaries of these data are displayed in near real time on the Syndromic Trends public website. We studied this dataset for the prevalence, seasonality, and coinfections of the 20 respiratory pathogens detected in over 362,000 patient samples acquired as a standard-of-care testing over the last 4 years from 20 clinical laboratories in the United States. RESULTS: The majority of pathogens show influenza-like seasonality, rhinovirus has fall and spring peaks, and adenovirus and the bacterial pathogens show constant detection over the year. The dataset can also be considered in an ecological framework; the viruses and bacteria detected by this test are parasites of a host (the human patient). Interestingly, the rate of pathogen codetections, on average 7.94% (28,741/362,101), matches predictions based on the relative abundance of organisms present. CONCLUSIONS: Syndromic Trends preserves patient privacy by removing or obfuscating patient identifiers while still collecting much useful information about the bacterial and viral pathogens that they harbor. Test results are uploaded to the database within a few hours of completion compared with delays of up to 10 days for other diagnostic-based reporting systems. This work shows that the barriers to establishing epidemiology systems are no longer scientific and technical but rather administrative, involving questions of patient privacy and data ownership. We have demonstrated here that these barriers can be overcome. This first look at the resulting data stream suggests that Syndromic Trends will be able to provide high-resolution analysis of circulating respiratory pathogens and may aid in the detection of new outbreaks.

20.
J Pediatr Pharmacol Ther ; 23(3): 203-208, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29970976

RESUMO

OBJECTIVE: This study was conducted to evaluate the impact of education on optimizing medication histories in a single-center pediatric emergency department. METHODS: This was a prospective, 2-phase study of 200 patients ages 21 years and younger who presented to the pediatric emergency department in January and February 2017. In phase I of the study, 100 patients were interviewed by both a nurse and a pharmacist. Between phases I and II, the pharmacist educated each nurse and disseminated standardized education materials. In phase II, 100 additional patients were interviewed by both a nurse and a pharmacist. Discrepancies were quantified in both phases of the study. The primary outcome was the distribution of total discrepancies in medications identified. Total discrepancies were defined as a composite of medication name, dose, route, frequency, and time of last dose. RESULTS: A total of 200 medication histories were collected over phases I and II. In phase I (n = 79), the pharmacist identified 185 medications, 88 of which were also identified by the nurse. In phase II (n = 82), the pharmacist identified 180 medications, 95 of which were also identified by the nurse. The distribution of discrepancies per patient and per medication was significantly reduced in regard to dose, route, and frequency documentation. CONCLUSION: Although improvement was observed, barriers beyond a knowledge deficit exist to limit accuracy of medication histories collected by nurses.

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