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1.
Proc Natl Acad Sci U S A ; 121(10): e2310852121, 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38416678

RESUMO

Enterococci are gut microbes of most land animals. Likely appearing first in the guts of arthropods as they moved onto land, they diversified over hundreds of millions of years adapting to evolving hosts and host diets. Over 60 enterococcal species are now known. Two species, Enterococcus faecalis and Enterococcus faecium, are common constituents of the human microbiome. They are also now leading causes of multidrug-resistant hospital-associated infection. The basis for host association of enterococcal species is unknown. To begin identifying traits that drive host association, we collected 886 enterococcal strains from widely diverse hosts, ecologies, and geographies. This identified 18 previously undescribed species expanding genus diversity by >25%. These species harbor diverse genes including toxins and systems for detoxification and resource acquisition. Enterococcus faecalis and E. faecium were isolated from diverse hosts highlighting their generalist properties. Most other species showed a more restricted distribution indicative of specialized host association. The expanded species diversity permitted the Enterococcus genus phylogeny to be viewed with unprecedented resolution, allowing features to be identified that distinguish its four deeply rooted clades, and the entry of genes associated with range expansion such as B-vitamin biosynthesis and flagellar motility to be mapped to the phylogeny. This work provides an unprecedentedly broad and deep view of the genus Enterococcus, including insights into its evolution, potential new threats to human health, and where substantial additional enterococcal diversity is likely to be found.


Assuntos
Enterococcus faecium , Infecções por Bactérias Gram-Positivas , Animais , Humanos , Enterococcus/genética , Antibacterianos/farmacologia , Enterococcus faecium/genética , Enterococcus faecalis/genética , Filogenia , Testes de Sensibilidade Microbiana , Farmacorresistência Bacteriana
2.
J Transl Med ; 22(1): 256, 2024 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-38461265

RESUMO

BACKGROUND: Children with cancer receiving chemotherapy commonly report a cluster of psychoneurological symptoms (PNS), including pain, fatigue, anxiety, depression, and cognitive dysfunction. The role of the gut microbiome and its functional metabolites in PNS is rarely studied among children with cancer. This study investigated the associations between the gut microbiome-metabolome pathways and PNS in children with cancer across chemotherapy as compared to healthy children. METHODS: A case-control study was conducted. Cancer cases were recruited from Children's Healthcare of Atlanta and healthy controls were recruited via flyers. Participants reported PNS using the Pediatric Patient-Reported Outcomes Measurement Information System. Data for cases were collected pre-cycle two chemotherapy (T0) and post-chemotherapy (T1), whereas data for healthy controls were collected once. Gut microbiome and its metabolites were measured using fecal specimens. Gut microbiome profiling was performed using 16S rRNA V4 sequencing, and metabolome was performed using an untargeted liquid chromatography-mass spectrometry approach. A multi-omics network integration program analyzed microbiome-metabolome pathways of PNS. RESULTS: Cases (n = 21) and controls (n = 14) had mean ages of 13.2 and 13.1 years. For cases at T0, PNS were significantly associated with microbial genera (e.g., Ruminococcus, Megasphaera, and Prevotella), which were linked with carnitine shuttle (p = 0.0003), fatty acid metabolism (p = 0.001) and activation (p = 0.001), and tryptophan metabolism (p = 0.008). Megasphaera, clustered with aspartate and asparagine metabolism (p = 0.034), carnitine shuttle (p = 0.002), and tryptophan (p = 0.019), was associated with PNS for cases at T1. Gut bacteria with potential probiotic functions, along with fatty acid metabolism, tryptophan, and carnitine shuttle, were more clustered in cancer cases than the control network and this linkage with PNS needs further studies. CONCLUSIONS: Using multi-omics approaches, this study indicated specific microbiome-metabolome pathways linked with PNS in children with cancer across chemotherapy. Due to limitations such as antibiotic use in cancer cases, these findings need to be further confirmed in a larger cohort.


Assuntos
Microbioma Gastrointestinal , Neoplasias , Humanos , Criança , Microbioma Gastrointestinal/genética , Metabolômica/métodos , Síndrome , Multiômica , Triptofano , RNA Ribossômico 16S/genética , Estudos de Casos e Controles , Metaboloma , Neoplasias/complicações , Neoplasias/tratamento farmacológico , Ácidos Graxos , Carnitina/análise , Fezes/microbiologia
3.
Proc Natl Acad Sci U S A ; 118(48)2021 11 30.
Artigo em Inglês | MEDLINE | ID: mdl-34819373

RESUMO

A protracted outbreak of New Delhi metallo-ß-lactamase (NDM)-producing carbapenem-resistant Klebsiella pneumoniae started in Tuscany, Italy, in November 2018 and continued in 2020 and through 2021. To understand the regional emergence and transmission dynamics over time, we collected and sequenced the genomes of 117 extensively drug-resistant, NDM-producing K. pneumoniae isolates cultured over a 20-mo period from 76 patients at several healthcare facilities in southeast Tuscany. All isolates belonged to high-risk clone ST-147 and were typically nonsusceptible to all first-line antibiotics. Albeit sporadic, resistances to colistin, tigecycline, and fosfomycin were also observed as a result of repeated, independent mutations. Genomic analysis revealed that ST-147 isolates circulating in Tuscany were monophyletic and highly genetically related (including a network of 42 patients from the same hospital and sharing nearly identical isolates), and shared a recent ancestor with clinical isolates from the Middle East. While the blaNDM-1 gene was carried by an IncFIB-type plasmid, our investigations revealed that the ST-147 lineage from Italy also acquired a hybrid IncFIB/IncHIB-type plasmid carrying the 16S methyltransferase armA gene as well as key virulence biomarkers often found in hypervirulent isolates. This plasmid shared extensive homologies with mosaic plasmids circulating globally including from ST-11 and ST-307 convergent lineages. Phenotypically, the carriage of this hybrid plasmid resulted in increased siderophore production but did not confer virulence to the level of an archetypical, hypervirulent K. pneumoniae in a subcutaneous model of infection with immunocompetent CD1 mice. Our findings highlight the importance of performing genomic surveillance to identify emerging threats.


Assuntos
Surtos de Doenças , Farmacorresistência Bacteriana Múltipla/genética , Infecções por Klebsiella/epidemiologia , Klebsiella pneumoniae/genética , Animais , Antibacterianos , Proteínas de Bactérias/genética , Biomarcadores , Carbapenêmicos , Colistina , Biologia Computacional/métodos , Infecção Hospitalar/epidemiologia , Humanos , Itália/epidemiologia , Estimativa de Kaplan-Meier , Funções Verossimilhança , Camundongos , Testes de Sensibilidade Microbiana , Preparações Farmacêuticas , Plasmídeos , Polimorfismo de Nucleotídeo Único , beta-Lactamases/genética
4.
Euro Surveill ; 29(24)2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38873796

RESUMO

In 2003-2023, amid 5,436 Acinetobacter baumannii isolates collected globally through the Multidrug-Resistant Organism Repository and Surveillance Network, 97 were ST19PAS, 34 of which carbapenem-resistant. Strains (n = 32) sampled after 2019 harboured either bla OXA-23, bla OXA-72, and/or bla NDM-5. Phylogenetic analysis of the 97 isolates and 11 publicly available ST19 genomes revealed three sub-lineages of carbapenemase-producing isolates from mainly Ukraine and Georgia, including an epidemic clone carrying all three carbapenemase genes. Infection control and global surveillance of carbapenem-resistant A. baumannii remain important.


Assuntos
Infecções por Acinetobacter , Acinetobacter baumannii , Proteínas de Bactérias , Testes de Sensibilidade Microbiana , beta-Lactamases , beta-Lactamases/genética , Acinetobacter baumannii/genética , Acinetobacter baumannii/isolamento & purificação , Acinetobacter baumannii/efeitos dos fármacos , Acinetobacter baumannii/enzimologia , Humanos , Infecções por Acinetobacter/microbiologia , Infecções por Acinetobacter/epidemiologia , Proteínas de Bactérias/genética , Ucrânia/epidemiologia , Antibacterianos/farmacologia , Carbapenêmicos/farmacologia , Filogenia , Farmacorresistência Bacteriana Múltipla/genética , República da Geórgia/epidemiologia , Tipagem de Sequências Multilocus
5.
Emerg Infect Dis ; 29(8): 1692-1695, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37406356

RESUMO

Blood and surveillance cultures from an injured service member from Ukraine grew Acinetobacter baumannii, Klebsiella pneumoniae, Enterococcus faecium, and 3 distinct Pseudomonas aeruginosa strains. Isolates were nonsusceptible to most antibiotics and carried an array of antibiotic resistant genes, including carbapenemases (blaIMP-1, blaNDM-1, blaOXA-23, blaOXA-48, blaOXA-72) and 16S methyltransferases (armA and rmtB4).


Assuntos
Acinetobacter baumannii , Militares , Humanos , Ucrânia/epidemiologia , Testes de Sensibilidade Microbiana , Antibacterianos/farmacologia , Bactérias/genética , beta-Lactamases/genética , Farmacorresistência Bacteriana Múltipla/genética
6.
Am Heart J ; 253: 76-85, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-35841944

RESUMO

BACKGROUND: Despite guideline recommendations to optimize low-density lipoprotein cholesterol (LDL-C) reduction with intensification of lipid-lowering therapy (LLT) in patients with atherosclerotic cardiovascular disease (ASCVD), few of these patients achieve LDL-C < 70 mg/dL in practice. PURPOSE: We developed a real-time, targeted electronic health record (EHR) alert with embedded ordering capability to promote intensification of evidence based LLT in outpatients with very high risk ASCVD. METHODS: We designed a pragmatic, multicenter, single-blind, cluster randomized trial to test the effectiveness of an EHR-based LLT intensification alert. The study will enroll about 100 providers who will be randomized to either receive the alert or undergo usual care for outpatients with high risk ASCVD with LDL-C > 70 mg/dL. Total enrollment will include 2,500 patients. The primary outcome will be the proportion of patients with LLT intensification at 90 days. Secondary outcomes include achieved LDL-C at 6 months and the proportion of patients with LDL-C < 70 mg/dL or < 55 mg/dL at 6 months. RESULTS: Enrollment of 1,250 patients (50% of goal) was reached within 47 days (50% women, mean age 72, median LDL-C 91). At baseline, 71%, 9%, and 3% were on statins, ezetimibe, or proprotein convertase subtilisin/kexin type 9 inhibitors, respectively. CONCLUSIONS: PRagmatic Trial of Messaging to Providers about Treatment of HyperLIPIDemia has rapidly reached 50% enrollment of patients with very high risk ASCVD, demonstrating low baseline LLT utilization. This pragmatic, EHR-based trial will determine the effectiveness of a real-time, targeted EHR alert with embedded ordering capability to promote LLT intensification. Findings from this low-cost, widely scalable intervention to improve LDL-C may have important public health implications. TRIAL REGISTRATION: clinicaltrials.gov NCT04394715.


Assuntos
Aterosclerose , Doenças Cardiovasculares , Hiperlipidemias , Idoso , Anticolesterolemiantes/uso terapêutico , Aterosclerose/complicações , Doenças Cardiovasculares/complicações , LDL-Colesterol , Feminino , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Hiperlipidemias/complicações , Hiperlipidemias/tratamento farmacológico , Masculino , Estudos Multicêntricos como Assunto , Pacientes Ambulatoriais , Ensaios Clínicos Pragmáticos como Assunto , Método Simples-Cego
7.
Magn Reson Med ; 85(2): 802-817, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-32820572

RESUMO

PURPOSE: Two-dimensional creatine CEST (2D-CrCEST), with a slice thickness of 10-20 mm and temporal resolution (τRes ) of about 30 seconds, has previously been shown to capture the creatine-recovery kinetics in healthy controls and in patients with abnormal creatine-kinase kinetics following the mild plantar flexion exercise. Since the distribution of disease burden may vary across the muscle length for many musculoskeletal disorders, there is a need to increase coverage in the slice-encoding direction. Here, we demonstrate the feasibility of 3D-CrCEST with τRes of about 30 seconds, and propose an improved voxel-wise B1+ -calibration approach for CrCEST. METHODS: The current 7T study with enrollment of 5 volunteers involved collecting the baseline CrCEST imaging for the first 2 minutes, followed by 2 minutes of plantar flexion exercise and then 8 minutes of postexercise CrCEST imaging, to detect the temporal evolution of creatine concentration following exercise. RESULTS: Very good repeatability of 3D-CrCEST findings for activated muscle groups on an intraday and interday basis was established, with coefficient of variance of creatine recovery constants (τCr ) being 7%-15.7%, 7.5%, and 5.8% for lateral gastrocnemius, medial gastrocnemius, and peroneus longus, respectively. We also established a good intraday and interday scan repeatability for 3D-CrCEST and also showed good correspondence between τCr measurements using 2D-CrCEST and 3D-CrCEST acquisitions. CONCLUSION: In this study, we demonstrated for the first time the feasibility and the repeatability of the 3D-CrCEST method in calf muscle with improved B1+ correction to measure creatine-recovery kinetics within a large 3D volume of calf muscle.


Assuntos
Creatina , Imageamento por Ressonância Magnética , Exercício Físico , Humanos , Cinética , Músculo Esquelético/diagnóstico por imagem
8.
Am J Kidney Dis ; 77(4): 490-499.e1, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33422598

RESUMO

RATIONALE & OBJECTIVE: Although coronavirus disease 2019 (COVID-19) has been associated with acute kidney injury (AKI), it is unclear whether this association is independent of traditional risk factors such as hypotension, nephrotoxin exposure, and inflammation. We tested the independent association of COVID-19 with AKI. STUDY DESIGN: Multicenter, observational, cohort study. SETTING & PARTICIPANTS: Patients admitted to 1 of 6 hospitals within the Yale New Haven Health System between March 10, 2020, and August 31, 2020, with results for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testing via polymerase chain reaction of a nasopharyngeal sample. EXPOSURE: Positive test for SARS-CoV-2. OUTCOME: AKI by KDIGO (Kidney Disease: Improving Global Outcomes) criteria. ANALYTICAL APPROACH: Evaluated the association of COVID-19 with AKI after controlling for time-invariant factors at admission (eg, demographic characteristics, comorbidities) and time-varying factors updated continuously during hospitalization (eg, vital signs, medications, laboratory results, respiratory failure) using time-updated Cox proportional hazard models. RESULTS: Of the 22,122 patients hospitalized, 2,600 tested positive and 19,522 tested negative for SARS-CoV-2. Compared with patients who tested negative, patients with COVID-19 had more AKI (30.6% vs 18.2%; absolute risk difference, 12.5% [95% CI, 10.6%-14.3%]) and dialysis-requiring AKI (8.5% vs 3.6%) and lower rates of recovery from AKI (58% vs 69.8%). Compared with patients without COVID-19, patients with COVID-19 had higher inflammatory marker levels (C-reactive protein, ferritin) and greater use of vasopressors and diuretic agents. Compared with patients without COVID-19, patients with COVID-19 had a higher rate of AKI in univariable analysis (hazard ratio, 1.84 [95% CI, 1.73-1.95]). In a fully adjusted model controlling for demographic variables, comorbidities, vital signs, medications, and laboratory results, COVID-19 remained associated with a high rate of AKI (adjusted hazard ratio, 1.40 [95% CI, 1.29-1.53]). LIMITATIONS: Possibility of residual confounding. CONCLUSIONS: COVID-19 is associated with high rates of AKI not fully explained by adjustment for known risk factors. This suggests the presence of mechanisms of AKI not accounted for in this analysis, which may include a direct effect of COVID-19 on the kidney or other unmeasured mediators. Future studies should evaluate the possible unique pathways by which COVID-19 may cause AKI.


Assuntos
Injúria Renal Aguda/epidemiologia , COVID-19/epidemiologia , Injúria Renal Aguda/sangue , Injúria Renal Aguda/terapia , Idoso , Proteína C-Reativa/metabolismo , COVID-19/metabolismo , COVID-19/terapia , Estudos de Coortes , Creatinina/sangue , Diuréticos/uso terapêutico , Feminino , Mortalidade Hospitalar , Humanos , Unidades de Terapia Intensiva , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Diálise Renal , Insuficiência Renal Crônica/sangue , Insuficiência Renal Crônica/epidemiologia , Respiração Artificial , Fatores de Risco , SARS-CoV-2 , Índice de Gravidade de Doença , Estados Unidos/epidemiologia , Vasoconstritores/uso terapêutico
9.
Cereb Cortex ; 30(3): 1830-1842, 2020 03 14.
Artigo em Inglês | MEDLINE | ID: mdl-31599922

RESUMO

Cigarette smoking during pregnancy is a major public health concern, resulting in detrimental health effects in the mother and her offspring. The adverse behavioral consequences for children include increased risk for attention deficit hyperactivity disorder, working memory deficits, epilepsy, novelty-seeking, and risk-taking behaviors. Some of these behavioral conditions are consistent with an imbalance in frontal cortical excitatory (glutamate) and inhibitory (GABA) neurotransmitter signaling. We used a GAD67-GFP knock-in mouse model to examine if developmental nicotine exposure alters frontal cortical GABA neuron numbers, GABA-to-non-GABA neuron ratio and behavioral phenotypes. Female mice were exposed to nicotine (100 or 200 µg/mL) in drinking water beginning 3 weeks prior to breeding and until 3 weeks postpartum. Male and female offspring were examined beginning at 60 days of age. The nicotine exposure produced dose-dependent decreases in GABA-to-non-GABA neuron ratios in the prefrontal and medial prefrontal cortices without perturbing the intrinsic differences in cortical thickness and laminar distribution of GABA or non-GABA neurons between these regions. A significant increase in exploratory behavior and a shift toward "approach" in the approach-avoidance paradigm were also observed. Thus, developmental nicotine exposure shifts the cortical excitation-inhibition balance toward excitation and produces behavioral changes consistent with novelty-seeking behavior.


Assuntos
Comportamento Exploratório/efeitos dos fármacos , Neurônios GABAérgicos/efeitos dos fármacos , Nicotina/farmacologia , Agonistas Nicotínicos/farmacologia , Animais , Comportamento Animal/efeitos dos fármacos , Modelos Animais de Doenças , Feminino , Lobo Frontal/efeitos dos fármacos , Transtornos da Memória/complicações , Memória de Curto Prazo/efeitos dos fármacos , Camundongos , Córtex Pré-Frontal/efeitos dos fármacos , Gravidez , Efeitos Tardios da Exposição Pré-Natal
10.
Dig Dis Sci ; 66(7): 2240-2249, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-32797346

RESUMO

BACKGROUND: Adult liver-related hospitalizations have recently increased in the USA, but data are limited for the pediatric population. AIMS: Utilizing the Office of Statewide Health Planning and Development hospital claims database (covering > 98% of all California hospitalizations), we aimed to characterize the demographic, clinical, and socioeconomic factors of liver disease-associated admissions among children between 2005 and 2015. METHODS: We used ICD-9 codes to identify admissions associated with liver disease in patients up to 21 years of age. Patient characteristics were described as percentages and evaluated using the χ2 test. We used linear regression to examine changes over time. RESULTS: We analyzed 37,372 eligible admissions. Overall, close to one-third (28%) and one-half (48.0%) of admissions occurred in the age group 0-5 years and 16-21 years, respectively, with the remaining 23.1% occurring in the age group between 5 and 15 years. Over half (54.9%) were in males. By race, blacks made up half of the admission (49.7%), while by ethnicity, Hispanic also accounted for half of the admission (49.7%). Medicaid and Medicare payors were also disproportionately represented (54.6%). The most common liver disease was Alagille syndrome (29.2%) in 2005. Between 2005 and 2015, both the number of pediatric liver-associated admissions and the proportion of pediatric liver admissions over total admissions increased from 3130 to 3429 and 1.2% to 1.6%, respectively (both p = 0.001). By 2015, while Alagille syndrome admissions decreased to 26.4% (p = 0.004), NAFLD admission increased to 19.7% (p < 0.001). CONCLUSION: Major disparities exist in inpatient liver disease burden for blacks and Hispanics with liver disease, while NAFLD emerged as a rapidly rising liver disease in pediatrics.


Assuntos
Hospitalização/tendências , Hepatopatias/epidemiologia , Grupos Raciais , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Medicaid , Medicare , Fatores Socioeconômicos , Estados Unidos , Adulto Jovem
11.
J Am Soc Nephrol ; 31(6): 1348-1357, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32381598

RESUMO

BACKGROUND: Timely prediction of AKI in children can allow for targeted interventions, but the wealth of data in the electronic health record poses unique modeling challenges. METHODS: We retrospectively reviewed the electronic medical records of all children younger than 18 years old who had at least two creatinine values measured during a hospital admission from January 2014 through January 2018. We divided the study population into derivation, and internal and external validation cohorts, and used five feature selection techniques to select 10 of 720 potentially predictive variables from the electronic health records. Model performance was assessed by the area under the receiver operating characteristic curve in the validation cohorts. The primary outcome was development of AKI (per the Kidney Disease Improving Global Outcomes creatinine definition) within a moving 48-hour window. Secondary outcomes included severe AKI (stage 2 or 3), inpatient mortality, and length of stay. RESULTS: Among 8473 encounters studied, AKI occurred in 516 (10.2%), 207 (9%), and 27 (2.5%) encounters in the derivation, and internal and external validation cohorts, respectively. The highest-performing model used a machine learning-based genetic algorithm, with an overall receiver operating characteristic curve in the internal validation cohort of 0.76 [95% confidence interval (CI), 0.72 to 0.79] for AKI, 0.79 (95% CI, 0.74 to 0.83) for severe AKI, and 0.81 (95% CI, 0.77 to 0.86) for neonatal AKI. To translate this prediction model into a clinical risk-stratification tool, we identified high- and low-risk threshold points. CONCLUSIONS: Using various machine learning algorithms, we identified and validated a time-updated prediction model of ten readily available electronic health record variables to accurately predict imminent AKI in hospitalized children.


Assuntos
Injúria Renal Aguda/etiologia , Adolescente , Criança , Criança Hospitalizada , Pré-Escolar , Registros Eletrônicos de Saúde , Feminino , Humanos , Lactente , Aprendizado de Máquina , Masculino , Estudos Retrospectivos
12.
J Appl Clin Med Phys ; 22(6): 11-15, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34018313

RESUMO

The American Association of Physicists in Medicine (AAPM) is a nonprofit professional society whose primary purposes are to advance the science, education and professional practice of medical physics. The AAPM has more than 8,000 members and is the principal organization of medical physicists in the United States. The AAPM will periodically define new practice guidelines for medical physics practice to help advance the science of medical physics and to improve the quality of service to patients throughout the United States. Existing medical physics practice guidelines will be reviewed for the purpose of revision or renewal, as appropriate, on their fifth anniversary or sooner. Each medical physics practice guideline represents a policy statement by the AAPM, has undergone a thorough consensus process in which it has been subjected to extensive review, and requires the approval of the Professional Council. The medical physics practice guidelines recognize that the safe and effective use of diagnostic and therapeutic radiology requires specific training, skills, and techniques, as described in each document. Reproduction or modification of the published practice guidelines and technical standards by those entities not providing these services is not authorized. The following terms are used in the AAPM practice guidelines: (1) Must and Must Not: Used to indicate that adherence to the recommendation is considered necessary to conform to this practice guideline. (2) Should and Should Not: Used to indicate a prudent practice to which exceptions may occasionally be made in appropriate circumstances.


Assuntos
Física Médica , Radioterapia (Especialidade) , Humanos , Sociedades , Estados Unidos
13.
Am J Kidney Dis ; 76(6): 806-814.e1, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32505812

RESUMO

RATIONALE & OBJECTIVE: Acute kidney injury (AKI) is diagnosed based on changes in serum creatinine concentration, a late marker of this syndrome. Algorithms that predict elevated risk for AKI are of great interest, but no studies have incorporated such an algorithm into the electronic health record to assist with clinical care. We describe the experience of implementing such an algorithm. STUDY DESIGN: Prospective observational cohort study. SETTING & PARTICIPANTS: 2,856 hospitalized adults in a single urban tertiary-care hospital with an algorithm-predicted risk for AKI in the next 24 hours>15%. Alerts were also used to target a convenience sample of 100 patients for measurement of 16 urine and 6 blood biomarkers. EXPOSURE: Clinical characteristics at the time of pre-AKI alert. OUTCOME: AKI within 24 hours of pre-AKI alert (AKI24). ANALYTICAL APPROACH: Descriptive statistics and univariable associations. RESULTS: At enrollment, mean predicted probability of AKI24 was 19.1%; 18.9% of patients went on to develop AKI24. Outcomes were generally poor among this population, with 29% inpatient mortality among those who developed AKI24 and 14% among those who did not (P<0.001). Systolic blood pressure<100mm Hg (28% of patients with AKI24 vs 18% without), heart rate>100 beats/min (32% of patients with AKI24 vs 24% without), and oxygen saturation<92% (15% of patients with AKI24 vs 6% without) were all more common among those who developed AKI24. Of all biomarkers measured, only hyaline casts on urine microscopy (72% of patients with AKI24 vs 25% without) and fractional excretion of urea nitrogen (20% [IQR, 12%-36%] among patients with AKI24 vs 34% [IQR, 25%-44%] without) differed between those who did and did not develop AKI24. LIMITATIONS: Single-center study, reliance on serum creatinine level for AKI diagnosis, small number of patients undergoing biomarker evaluation. CONCLUSIONS: A real-time AKI risk model was successfully integrated into the EHR.


Assuntos
Injúria Renal Aguda/diagnóstico , Creatinina/sangue , Pacientes Internados , Medição de Risco/métodos , Injúria Renal Aguda/sangue , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Nitrogênio da Ureia Sanguínea , Progressão da Doença , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Curva ROC , Índice de Gravidade de Doença
14.
Biometrics ; 76(1): 257-269, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31350904

RESUMO

The field of neuroimaging dedicated to mapping connections in the brain is increasingly being recognized as key for understanding neurodevelopment and pathology. Networks of these connections are quantitatively represented using complex structures, including matrices, functions, and graphs, which require specialized statistical techniques for estimation and inference about developmental and disorder-related changes. Unfortunately, classical statistical testing procedures are not well suited to high-dimensional testing problems. In the context of global or regional tests for differences in neuroimaging data, traditional analysis of variance (ANOVA) is not directly applicable without first summarizing the data into univariate or low-dimensional features, a process that might mask the salient features of high-dimensional distributions. In this work, we consider a general framework for two-sample testing of complex structures by studying generalized within-group and between-group variances based on distances between complex and potentially high-dimensional observations. We derive an asymptotic approximation to the null distribution of the ANOVA test statistic, and conduct simulation studies with scalar and graph outcomes to study finite sample properties of the test. Finally, we apply our test to our motivating study of structural connectivity in autism spectrum disorder.


Assuntos
Biometria/métodos , Conectoma/estatística & dados numéricos , Adolescente , Análise de Variância , Transtorno do Espectro Autista/diagnóstico por imagem , Criança , Simulação por Computador , Interpretação Estatística de Dados , Imagem de Tensor de Difusão/estatística & dados numéricos , Humanos
15.
J Appl Clin Med Phys ; 21(7): 11-15, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31800151

RESUMO

The American Association of Physicists in Medicine (AAPM) is a nonprofit professional society whose primary purposes are to advance the science, education and professional practice of medical physics. The AAPM has more than 8,000 members and is the principal organization of medical physicists in the United States. The AAPM will periodically define new practice guidelines for medical physics practice to help advance the science of medical physics and to improve the quality of service to patients throughout the United States. Existing medical physics practice guidelines will be reviewed for the purpose of revision or renewal, as appropriate, on their fifth anniversary or sooner. Each medical physics practice guideline represents a policy statement by the AAPM, has undergone a thorough consensus process in which it has been subjected to extensive review, and requires the approval of the Professional Council. The medical physics practice guidelines recognize that the safe and effective use of diagnostic and therapeutic radiology requires specific training, skills, and techniques, as described in each document. Reproduction or modification of the published practice guidelines and technical standards by those entities not providing these services is not authorized. The following terms are used in the AAPM practice guidelines: Must and Must Not: Used to indicate that adherence to the recommendation is considered necessary to conform to this practice guideline. Should and Should Not: Used to indicate a prudent practice to which exceptions may occasionally be made in appropriate circumstances. Approved by AAPM's Executive Committee May 28, 2019.


Assuntos
Física Médica , Radioterapia (Especialidade) , Humanos , Sociedades , Estados Unidos
16.
PLoS Med ; 16(7): e1002861, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31306408

RESUMO

BACKGROUND: Acute kidney injury (AKI) is an adverse event that carries significant morbidity. Given that interventions after AKI occurrence have poor performance, there is substantial interest in prediction of AKI prior to its diagnosis. However, integration of real-time prognostic modeling into the electronic health record (EHR) has been challenging, as complex models increase the risk of error and complicate deployment. Our goal in this study was to create an implementable predictive model to accurately predict AKI in hospitalized patients and could be easily integrated within an existing EHR system. METHODS AND FINDINGS: We performed a retrospective analysis looking at data of 169,859 hospitalized adults admitted to one of three study hospitals in the United States (in New Haven and Bridgeport, Connecticut) from December 2012 to February 2016. Demographics, medical comorbidities, hospital procedures, medications, and laboratory data were used to develop a model to predict AKI within 24 hours of a given observation. Outcomes of AKI severity, requirement for renal replacement therapy, and mortality were also measured and predicted. Models were trained using discrete-time logistic regression in a subset of Hospital 1, internally validated in the remainder of Hospital 1, and externally validated in Hospital 2 and Hospital 3. Model performance was assessed via the area under the receiver-operator characteristic (ROC) curve (AUC). The training set cohort contained 60,701 patients, and the internal validation set contained 30,599 patients. External validation data sets contained 43,534 and 35,025 patients. Patients in the overall cohort were generally older (median age ranging from 61 to 68 across hospitals); 44%-49% were male, 16%-20% were black, and 23%-29% were admitted to surgical wards. In the training set and external validation set, 19.1% and 18.9% of patients, respectively, developed AKI. The full model, including all covariates, had good ability to predict imminent AKI for the validation set, sustained AKI, dialysis, and death with AUCs of 0.74 (95% CI 0.73-0.74), 0.77 (95% CI 0.76-0.78), 0.79 (95% CI 0.73-0.85), and 0.69 (95% CI 0.67-0.72), respectively. A simple model using only readily available, time-updated laboratory values had very similar predictive performance to the complete model. The main limitation of this study is that it is observational in nature; thus, we are unable to conclude a causal relationship between covariates and AKI and do not provide an optimal treatment strategy for those predicted to develop AKI. CONCLUSIONS: In this study, we observed that a simple model using readily available laboratory data could be developed to predict imminent AKI with good discrimination. This model may lend itself well to integration into the EHR without sacrificing the performance seen in more complex models.


Assuntos
Injúria Renal Aguda/epidemiologia , Técnicas de Apoio para a Decisão , Pacientes Internados , Admissão do Paciente/tendências , Injúria Renal Aguda/diagnóstico , Injúria Renal Aguda/mortalidade , Injúria Renal Aguda/terapia , Idoso , Idoso de 80 Anos ou mais , Connecticut/epidemiologia , Registros Eletrônicos de Saúde , Feminino , Mortalidade Hospitalar , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Diálise Renal , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Índice de Gravidade de Doença , Fatores de Tempo
17.
Artigo em Inglês | MEDLINE | ID: mdl-30397055

RESUMO

Lipopeptide daptomycin is a last-line cell-membrane-targeting antibiotic to treat multidrug-resistant Staphylococcus aureus Alarmingly, daptomycin-resistant S. aureus isolates have emerged. The mechanisms underlying daptomycin resistance are diverse and share similarities with resistances to cationic antimicrobial peptides and other lipopeptides, but they remain to be fully elucidated. We selected mutants with increased resistance to daptomycin from a library of transposon insertions in sequent type 8 (ST8) S. aureus HG003. Insertions conferring increased daptomycin resistance were localized to two genes, one coding for a hypothetical lipoprotein (SAOUHSC_00362, Dsp1), and the other for an alkaline shock protein (SAOUHSC_02441, Asp23). Markerless loss-of-function mutants were then generated for comparison. All transposon mutants and knockout strains exhibited increased daptomycin resistance compared to those of wild-type and complemented strains. Null and transposon insertion mutants also exhibited increased resistance to cationic antimicrobial peptides. Interestingly, the Δdsp1 mutant also showed increased resistance to vancomycin, a cell-wall-targeting drug with a different mode of action. Null mutations in both dsp1 and asp23 resulted in increased tolerance as reflected by reduced killing to both daptomycin and vancomycin, as well as an increased tolerance to surfactant (Triton X-100). Neither mutant exhibited increased resistance to lysostaphin, a cell-wall-targeting endopeptidase. These findings identified two genes core to the S. aureus species that make previously uncharacterized contributions to antimicrobial resistance and tolerance in S. aureus.


Assuntos
Antibacterianos/farmacologia , Proteínas de Bactérias/genética , Daptomicina/farmacologia , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/genética , Membrana Celular/efeitos dos fármacos , Elementos de DNA Transponíveis/genética , Farmacorresistência Bacteriana Múltipla/genética , Testes de Sensibilidade Microbiana , Infecções Estafilocócicas/tratamento farmacológico , Vancomicina/farmacologia
18.
J Environ Manage ; 232: 1012-1020, 2019 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-33395753

RESUMO

Carcinoscorpius rotundicauda and Tachypleus gigas may co-exist and share common spawning grounds elsewhere but at Balok (East Coast of Peninsular Malaysia), C. rotundicauda is an understudied species. Neglected as research candidate because of inaccessible spawning grounds, smaller size and less commercial value than T. gigas and also, difficulty to attain from the wild has made C. rotundicauda population status remaining unidentified at Balok. This standpoint drove the present attempt because anthropic activities like structure placement and mining are point-source for runoffs that load sediments into Balok River. While erosion-accretion events have altered Balok River width, the shore sediments in Balok Beach were transitioned between medium-fine and fine sand between years 2012 and 2016. Eventually by year 2016, the C. rotundicauda were depositing 5117 eggs in 91 nests from 200 to 1000 m range along this corridor facing South China Sea. From this yield, C. rotundicauda released 2880 eggs in 56 nests during the Southwest monsoon, 1254 eggs in 19 nests during the Northeast monsoon and 983 eggs in 16 nests during the Inter-monsoon seasons. Though female C. rotundicauda opted to lay their eggs in shallow burrows at lower shorelines, the absence of erosion and substantial silt and clay (>20%) deposition facilitates C. rotundicauda embryogenesis with brief periods of temperature and salinity shocks during day-time falling tides. This encourages C. rotundicauda to emerge with increasing abundance and carry out bi-monthly spawning at Balok Beach. In short, shore restoration initiatives like systematic boat docking, proper disposal of nets and waste and, periodic fish-catching operations were effectively led by the Balok fisher citizen scientist. This successful community joint-cooperation proves that citizen-led caretaking of degraded beaches offers marine life protection and are practical for coastal area management especially at areas where other oviparous animals such as turtles and crocodiles are harboured.

19.
J Appl Clin Med Phys ; 19(6): 11-25, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30338913

RESUMO

The American Association of Physicists in Medicine (AAPM) is a nonprofit professional society whose primary purposes are to advance the science, education, and professional practice of medical physics. The AAPM has more than 8000 members and is the principal organization of medical physicists in the United States. The AAPM will periodically define new practice guidelines for medical physics practice to help advance the science of medical physics and to improve the quality of service to patients throughout the United States. Existing medical physics practice guidelines will be reviewed for the purpose of revision or renewal, as appropriate, on their fifth anniversary or sooner. Each medical physics practice guideline (MPPG) represents a policy statement by the AAPM, has undergone a thorough consensus process in which it has been subjected to extensive review, and requires the approval of the Professional Council. The medical physics practice guidelines recognize that the safe and effective use of diagnostic and therapeutic radiation requires specific training, skills, and techniques as described in each document. As the review of the previous version of AAPM Professional Policy (PP)-17 (Scope of Practice) progressed, the writing group focused on one of the main goals: to have this document accepted by regulatory and accrediting bodies. After much discussion, it was decided that this goal would be better served through a MPPG. To further advance this goal, the text was updated to reflect the rationale and processes by which the activities in the scope of practice were identified and categorized. Lastly, the AAPM Professional Council believes that this document has benefitted from public comment which is part of the MPPG process but not the AAPM Professional Policy approval process. The following terms are used in the AAPM's MPPGs: Must and Must Not: Used to indicate that adherence to the recommendation is considered necessary to conform to this practice guideline. Should and Should Not: Used to indicate a prudent practice to which exceptions may occasionally be made in appropriate circumstances.


Assuntos
Física Médica/normas , Guias de Prática Clínica como Assunto/normas , Sociedades Científicas/normas , Humanos , Doses de Radiação
20.
J Pediatr Hematol Oncol ; 39(8): e446-e449, 2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-28306689

RESUMO

Pneumothorax is a well-described complication of osteosarcoma. Conversely, the presence of a pneumomediastinum to our knowledge has been reported just once in a patient with osteosarcoma, and never without detectable lung metastasis. We report the case of an 18-year-old male with a localized, distal femur osteosarcoma who was found to have an asymptomatic pneumomediastinum and pneumatocele at diagnosis, and then 16 months later experienced a pulmonary relapse. Our case suggests that these findings may represent the presence of occult metastatic disease and cautions providers to treat appropriately and provide surveillance with a high index of suspicion for pulmonary recurrence.


Assuntos
Neoplasias Ósseas/patologia , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/secundário , Mediastino/patologia , Osteossarcoma/patologia , Adolescente , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biópsia , Neoplasias Ósseas/diagnóstico , Neoplasias Ósseas/tratamento farmacológico , Terapia Combinada , Evolução Fatal , Humanos , Neoplasias Pulmonares/terapia , Masculino , Osteossarcoma/diagnóstico , Osteossarcoma/tratamento farmacológico , Tomografia por Emissão de Pósitrons , Tomografia Computadorizada por Raios X
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