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Per- and polyfluoroalkyl substances (PFAS) are ubiquitous throughout the United States. Previous studies have shown PFAS exposure to be associated with a reduced immune response. However, the relationship between serum PFAS and antibody levels following SARS-CoV-2 infection or COVID-19 vaccination has not been examined. We examined differences in peak immune response and the longitudinal decline of antibodies following SARS-CoV-2 infection and COVID-19 vaccination by serum PFAS levels in a cohort of essential workers in the United States. We measured serum antibodies using an in-house semi-quantitative enzyme-linked immunosorbent assay (ELISA). Two cohorts contributed blood samples following SARS-CoV-2 infection or COVID-19 vaccination. We used linear mixed regression models, adjusting for age, race/ethnicity, gender, presence of chronic conditions, location, and occupation, to estimate differences in immune response with respect to serum PFAS levels. Our study populations included 153 unvaccinated participants that contributed 316 blood draws over a 14-month period following infection, and 860 participants and 2451 blood draws over a 12-month period following vaccination. Higher perfluorooctane sulfonic acid (PFOS), perfluorohexane sulfonic acid (PFHxS), and perfluorononanoic acid (PFNA) concentrations were associated with a lower peak antibody response after infection (p = 0.009, 0.031, 0.015). Higher PFOS, perfluorooctanoic acid (PFOA), PFHxS, and PFNA concentrations were associated with slower declines in antibodies over time after infection (p = 0.003, 0.014, 0.026, 0.025). PFOA, PFOS, PFHxS, and PFNA serum concentrations prior to vaccination were not associated with differences in peak antibody response after vaccination or with differences in decline of antibodies over time after vaccination. These results suggest that elevated PFAS may impede potential immune response to SARS-CoV-2 infection by blunting peak antibody levels following infection; the same finding was not observed for immune response to vaccination.
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Ácidos Alcanossulfônicos , COVID-19 , Poluentes Ambientais , Fluorocarbonos , Humanos , Estados Unidos , SARS-CoV-2 , Vacinas contra COVID-19 , COVID-19/prevenção & controle , AnticorposRESUMO
BACKGROUND: Firefighters have occupational and environmental exposures to per- and polyfluoroalkyl substances (PFAS). The goal of this study was to compare serum PFAS concentrations across multiple United States fire departments to National Health and Nutrition Examination Survey (NHANES) participants. METHODS: Nine serum PFAS were compared in 290 firefighters from four municipal fire departments (coded A-D) and three NHANES participants matched to each firefighter on sex, ethnicity, age, and PFAS collection year. Only Departments A and C had sufficient women study participants (25 and six, respectively) to compare with NHANES. RESULTS: In male firefighters compared with NHANES, geometric mean perfluorohexane sulfonate (PFHxS) was elevated in Departments A-C, sum of branched perfluoromethylheptane sulfonate isomers (Sm-PFOS) was elevated in all four departments, linear perfluorooctane sulfonate (n-PFOS) was elevated in Departments B and C, linear perfluorooctanoate (n-PFOA) was elevated in Departments B-D, and perfluorononanoate (PFNA) was elevated in Departments B-D, but lower in A. In male firefighters compared with NHANES, perfluoroundecanoate (PFUnDA) was more frequently detected in Departments B and D, and 2-(N-methyl-perfluorooctane sulfonamido) acetate (MeFOSAA) was less frequently detected in Departments B-D. In female firefighters compared with NHANES, PFHxS and Sm-PFOS concentrations were elevated in Departments A and C. Other PFAS concentrations were elevated and/or reduced in only one department or not significantly different from NHANES in any department. CONCLUSIONS: Serum PFHxS, Sm-PFOS, n-PFOS, n-PFOA, and PFNA concentrations were increased in at least two of four fire departments in comparison to NHANES.
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Poluentes Ambientais , Fluorocarbonos , Humanos , Masculino , Feminino , Estados Unidos , Inquéritos Nutricionais , Fluorocarbonos/análise , Exposição Ambiental , AlcanossulfonatosRESUMO
BACKGROUND: Hospitalized patients with advanced heart failure often experience acute and/or chronic pain. While virtual reality has been extensively studied across a wide range of clinical settings, no studies have yet evaluated potential impact on pain management on this patient population. AIM: To investigate the impact of a virtual reality experience on self-reported pain, quality-of-life, general distress, and satisfaction compared to a two-dimensional guided imagery active control. DESIGN: Single-center prospective randomized controlled study. The primary outcome was the difference in pre- versus post-intervention self-reported pain scores on a numerical rating scale from 0 to 10. Secondary outcomes included changes in quality-of-life scores, general distress, and satisfaction with the intervention. SETTING/PARTICIPANTS: Between October 2018 and March 2020, 88 participants hospitalized with advanced heart failure were recruited from an urban tertiary academic medical center. RESULTS: Participants experienced significant improvement in pain score after either 10 minutes of virtual reality (change from pre- to post -2.9 ± 2.6, p < 0.0001) or 10 minutes of guided imagery (change from pre- to post -1.3 ± 1.8, p = 0.0001); the virtual reality arm experienced a 1.5 unit comparatively greater reduction in pain score compared to guided imagery (p = 0.0011). Total quality-of-life and general distress scores did not significantly change for either arm. Seventy-eight participants (89%) responded that they would be willing to use the assigned intervention again. CONCLUSION: Virtual reality may be an effective nonpharmacologic adjuvant pain management intervention in hospitalized patients with heart failure. TRIAL REGISTRATION: ClinicalTrials.gov database (NCT04572425).
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Dor Crônica , Insuficiência Cardíaca , Realidade Virtual , Insuficiência Cardíaca/terapia , Humanos , Manejo da Dor , Estudos ProspectivosRESUMO
HIV pre-exposure prophylaxis (PrEP) is underutilized among Hispanics, women, and low-income individuals. To better understand PrEP barriers in this population, questionnaires were administered to 500 patients attending public health clinics in southern Arizona which provide family planning and sexually transmitted infections care. Sixty-three percent believed that they had no risk of HIV infection. When asked "Before today, did you know that there was a pill that can prevent HIV infection?" 80% of persons answered no. Among women, 88% answered no to this question. As expected, individuals with a higher perceived HIV risk (OR 1.76) or one HIV risk factor (OR 5.85) had a higher probability of knowledge. Among survey participants 87% would take a daily pill, 91% would visit a health-care provider every 3 months, and 92% would have laboratory testing every 3 months. Fifty-four percent would not be afraid or embarrassed if friends or family knew they were taking PrEP. Seventy-two percent would take PrEP despite temporary nausea. Sixty-two percent would pay ≥ $40 every 3 months for PrEP. Lack of knowledge, rather than patient attitudes, is the more important barrier to wider utilization of PrEP among individuals, especially women, attending public health clinics in Southern Arizona. Future efforts need to focus on education and access to PrEP in underserved populations including women and Hispanics.
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Serviços de Saúde Comunitária , Infecções por HIV , Conhecimentos, Atitudes e Prática em Saúde , Profilaxia Pré-Exposição , Adulto , Arizona , Infecções por HIV/tratamento farmacológico , Infecções por HIV/prevenção & controle , Humanos , Inquéritos e QuestionáriosRESUMO
BACKGROUND: School-supervised use of a once-daily inhaled corticosteroid regimen (supervised therapy) can improve medication adherence and asthma control. OBJECTIVE: We sought to evaluate the effectiveness of supervised therapy in a unique setting and population. METHODS: We conducted a cluster randomized trial of supervised therapy in 20 elementary schools with a disproportionate enrollment of low-income Latino students. Schools were purposively selected, matched, and randomized to receive 9 months of supervised therapy with mometasone furoate or usual care. All English- or Spanish-speaking students with self-reported asthma were eligible. The Asthma Control Questionnaire (ACQ) was interviewer administered quarterly at school. Students in supervised therapy schools were hypothesized to have lower ACQ scores than students in usual-care schools. RESULTS: Of 393 enrolled students, 189 students receiving immediate intervention and 143 students receiving delayed intervention provided 1 or more ACQ data points, were between 6 and 10 years of age, and were included in the primary analysis. At baseline, 39% of students reported taking a controller medication, and 24% had well-controlled asthma. Eighty percent of students receiving immediate intervention were prescribed mometasone. Schools administered 98% of prescribed doses when students attended school. Absences, weekends, and holidays reduced calendar adherence to 53%. During the first year, the mean ACQ score for students receiving immediate and delayed intervention was 1.55 (95% CI, 1.41-1.70) and 1.64 (95% CI, 1.47-1.80), respectively. The estimated treatment effect was -0.08 (95% CI, -0.31 to 0.14). DISCUSSION: Compared with usual care, supervised therapy did not improve asthma control among this population of Latino students. Additional research is warranted to confirm these results.
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Corticosteroides/uso terapêutico , Antiasmáticos/uso terapêutico , Asma/tratamento farmacológico , Furoato de Mometasona/uso terapêutico , Serviços de Saúde Escolar/estatística & dados numéricos , Administração por Inalação , Asma/epidemiologia , Criança , Feminino , Humanos , Masculino , Adesão à Medicação , Pobreza , Instituições Acadêmicas , Inquéritos e Questionários , Estados Unidos/epidemiologiaRESUMO
Mechanisms of magnesium homeostasis in Mycobacterium tuberculosis are poorly understood. Here, we describe the characterization of a pyrimidinetrione amide scaffold that disrupts magnesium homeostasis in the pathogen by direct binding to the CorA Mg2+/Co2+ transporter. Mutations in domains of CorA that are predicted to regulate the pore opening in response to Mg2+ ions conferred resistance to this scaffold. The pyrimidinetrione amides were cidal against the pathogen under both actively replicating and nonreplicating conditions in vitro and were efficacious against the organism during macrophage infection. However, the compound lacked efficacy in infected mice, possibly due to limited exposure. Our results indicate that inhibition of Mg2+ homeostasis by CorA is an attractive target for tuberculosis drug discovery and encourage identification of improved CorA inhibitors.
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Proteínas de Bactérias/metabolismo , Proteínas de Transporte de Cátions/metabolismo , Magnésio/metabolismo , Mycobacterium tuberculosis/efeitos dos fármacos , Mycobacterium tuberculosis/metabolismo , Antibacterianos/química , Antibacterianos/farmacocinética , Antibacterianos/farmacologia , Proteínas de Bactérias/genética , Proteínas de Transporte de Cátions/genética , Homeostase/efeitos dos fármacos , Pirimidinas/química , Pirimidinas/farmacocinética , Pirimidinas/farmacologia , Relação Estrutura-AtividadeRESUMO
Speech sounds are encoded by distributed patterns of activity in bilateral superior temporal cortex. However, it is unclear whether speech sounds are topographically represented in cortex, or which acoustic or phonetic dimensions might be spatially mapped. Here, using functional MRI, we investigated the potential spatial representation of vowels, which are largely distinguished from one another by the frequencies of their first and second formants, i.e. peaks in their frequency spectra. This allowed us to generate clear hypotheses about the representation of specific vowels in tonotopic regions of auditory cortex. We scanned participants as they listened to multiple natural tokens of the vowels [É] and [i], which we selected because their first and second formants overlap minimally. Formant-based regions of interest were defined for each vowel based on spectral analysis of the vowel stimuli and independently acquired tonotopic maps for each participant. We found that perception of [É] and [i] yielded differential activation of tonotopic regions corresponding to formants of [É] and [i], such that each vowel was associated with increased signal in tonotopic regions corresponding to its own formants. This pattern was observed in Heschl's gyrus and the superior temporal gyrus, in both hemispheres, and for both the first and second formants. Using linear discriminant analysis of mean signal change in formant-based regions of interest, the identity of untrained vowels was predicted with â¼73% accuracy. Our findings show that cortical encoding of vowels is scaffolded on tonotopy, a fundamental organizing principle of auditory cortex that is not language-specific.
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Córtex Auditivo/fisiologia , Mapeamento Encefálico/métodos , Fonética , Percepção da Fala/fisiologia , Estimulação Acústica , Adulto , Feminino , Humanos , Imageamento por Ressonância Magnética/métodos , MasculinoRESUMO
A versatile synthetic protocol is reported that allows high concentrations of functionally active membrane proteins to be incorporated in mesostructured silica materials. Judicious selections of solvent, surfactant, silica precursor species, and synthesis conditions enable membrane proteins to be stabilized in solution and during subsequent coassembly into silica-surfactant composites with nano- and mesoscale order. This was demonstrated by using a combination of nonionic ( n-dodecyl-ß-d-maltoside or Pluronic P123), lipid-like (1,2-diheptanoyl- s n-glycero-3-phosphocholine), and perfluoro-octanoate surfactants under mild acidic conditions to coassemble the light-responsive transmembrane protein proteorhodopsin at concentrations up to 15 wt % into the hydrophobic regions of worm-like mesostructured silica materials in films. Small-angle X-ray scattering, electron paramagnetic resonance spectroscopy, and transient UV-visible spectroscopy analyses established that proteorhodopsin molecules in mesostructured silica films exhibited native-like function, as well as enhanced thermal stability compared to surfactant or lipid environments. The light absorbance properties and light-activated conformational changes of proteorhodopsin guests in mesostructured silica films are consistent with those associated with the native H+-pumping mechanism of these biomolecules. The synthetic protocol is expected to be general, as demonstrated also for the incorporation of functionally active cytochrome c, a peripheral membrane protein enzyme involved in electron transport, into mesostructured silica-cationic surfactant films.
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Citocromos c/química , Rodopsinas Microbianas/química , Dióxido de Silício/química , Citocromos c/metabolismo , Estrutura Molecular , Rodopsinas Microbianas/metabolismo , Dióxido de Silício/metabolismo , Tensoativos/química , Tensoativos/metabolismoRESUMO
In alpine ecosystems, nitrogen (N) deposition has been linked to plant community composition change, including loss of bryophytes and increase of graminoids. Since bryophyte growth is stimulated by increased N availability, it has been hypothesized that loss of bryophyte cover is driven by enhanced decomposition. As bryophyte mats are a significant carbon (C) store, their loss may impact C storage in these ecosystems. We used an N deposition gradient across 15 sites in the UK to examine effects of N deposition on bryophyte litter quality, decomposition and C and N stocks in Racomitrium moss-sedge heath. Increasing N deposition reduced C : N in bryophyte litter, which in turn enhanced decomposition. Soil N stocks increased significantly in response to increased N deposition, and soil C : N declined. However, depletion of the bryophyte mat and its replacement by graminoids under high N deposition was not associated with a change in total ecosystem C stocks. We conclude that decomposition processes in Racomitrium heath are very sensitive to N deposition and provide a mechanism by which N deposition drives depletion of the bryophyte mat. Nitrogen deposition did not measurably alter C stocks, but changes in soil N stocks and C : N suggest the ecosystem is becoming N saturated.
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Briófitas/metabolismo , Carbono/metabolismo , Nitrogênio/metabolismo , Biomassa , Geografia , Modelos Lineares , Folhas de Planta/fisiologia , Reino UnidoRESUMO
A two-step, one-flask reaction of pyrrole and pentafluorobenzaldehyde was investigated as a streamlined synthetic route to an N-confused porphyrin bearing pentafluorophenyl substituents previously prepared by a stepwise route. A survey of acid catalysts, acid catalyst concentration, DDQ quantity, and reaction time was performed with monitoring by HPLC. The targeted N-confused porphyrin was observed from many reaction conditions. The best condition afforded the N-confused porphyrin in an isolated yield of 10-12% (245-281 mg), providing improved access to this interesting porphyrinoid.
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Neutral and deprotonated anionic Ni(II), Pd(II), Cu(II), and Cu(III) complexes of tetrakis(perfluorophenyl)-N-confused porphyrin (PF-NCP) were prepared and investigated by UV-visible and magnetic circular dichroism (MCD) spectroscopies. As in the previously reported Ni(II) adduct of tetraphenyl N-confused porphyrin, we observe sign reverse (positive to negative intensities with increasing energy) features in the MCD spectra of the neutral Ni(II), Pd(II), and Cu(II) complexes of PF-NCP, which is indicative of rare ΔHOMO < ΔLUMO relationships. Upon deprotonation of Ni(II), Pd(II), and Cu(II) complexes, these features revert to those of more typical porphyrin MCD spectra consistent with a ΔHOMO > ΔLUMO condition. The Cu(III) PF-NCP complex shows features similar to those of the deprotonated divalent metal systems. Spectroscopic features in all target complexes as well as previously published metal-free and Ni(II) NCP systems were correlated with the density functional theory (DFT) and time-dependent DFT (TDDFT) calculations. Calculation data are consistent with the tautomeric rearrangement of the electronic structures of NCP cores playing dominant roles, with smaller contribution from the central metal ions in the observed optical and magneto-optical properties. This is true for all described NCP systems to date, as they affect the stabilization/destabilization of the N-confused porphyrin-centered Gouterman orbitals.
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Bioassays of planarian neoplasia highlight the potential of these organisms as useful standards to assess whether environmental toxins such as cadmium promote tumorigenesis. These studies complement other investigations into the exceptional healing and regeneration of planarians - processes that are driven by a population of active stem cells, or neoblasts, which are likely transformed during planarian tumor growth. Our goal was to determine if planarian tumorigenesis assays are amenable to mechanistic studies of cadmium carcinogenesis. To that end we demonstrate, by examining both counts of cell populations by size, and instances of mitosis, that the activity of the stem cell population can be monitored. We also provide evidence that specific biomodulators can affect the potential of planarian neoplastic growth, in that an inhibitor of metalloproteinases effectively blocked the development of the lesions. From these results, we infer that neoblast activity does respond to cadmium-induced tumor growth, and that metalloproteinases are required for the progression of cancer in the planarian.
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Cádmio/toxicidade , Carcinógenos/toxicidade , Transformação Celular Neoplásica/induzido quimicamente , Modelos Biológicos , Planárias/efeitos dos fármacos , Animais , Benchmarking , Testes de Carcinogenicidade , Transformação Celular Neoplásica/ultraestrutura , Cocarcinogênese , Mitose/efeitos dos fármacos , Planárias/citologia , Regeneração/efeitos dos fármacosRESUMO
BACKGROUND: The optimal strategy for initial respiratory support in patients with respiratory failure associated with COVID-19 is unclear, and the initial strategy may affect outcomes. RESEARCH QUESTION: Which initial respiratory support strategy is associated with improved outcomes in patients with COVID-19 with acute respiratory failure? STUDY DESIGN AND METHODS: All patients with COVID-19 requiring respiratory support and admitted to a large health care network were eligible for inclusion. We compared patients treated initially with noninvasive respiratory support (NIRS; noninvasive positive pressure ventilation by facemask or high-flow nasal oxygen) with patients treated initially with invasive mechanical ventilation (IMV). The primary outcome was time to in-hospital death analyzed using an inverse probability of treatment weighted Cox model adjusted for potential confounders. Secondary outcomes included unweighted and weighted assessments of mortality, lengths of stay (ICU and hospital), and time to intubation. RESULTS: Nearly one-half of the 2,354 patients (47%) who met inclusion criteria received IMV first, and 53% received initial NIRS. Overall, in-hospital mortality was 38% (37% for IMV and 39% for NIRS). Initial NIRS was associated with an increased hazard of death compared with initial IMV (hazard ratio, 1.42; 95% CI, 1.03-1.94), but also an increased hazard of leaving the hospital sooner that waned with time (noninvasive support by time interaction: hazard ratio, 0.97; 95% CI, 0.95-0.98). INTERPRETATION: Patients with COVID-19 with acute hypoxemic respiratory failure initially treated with NIRS showed an increased hazard of in-hospital death.
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OBJECTIVE: Firefighters are occupationally exposed to per- and polyfluoroalkyl substances (PFAS). This study objective was to compare serum PFAS concentrations in incumbent and recruit firefighters and evaluate temporal trends among recruits. METHODS: Serum PFAS concentrations were measured in 99 incumbent and 55 recruit firefighters at enrollment in 2015-2016, with follow-up 20 to 37 months later for recruits. Linear and logistic regression and linear mixed-effects models were used for analyses. Fireground exposure impact on PFAS concentrations was investigated using adjusted linear and logistic regression models. RESULTS: Incumbents had lower n-PFOA and PFNA than recruits and most PFAS significantly decreased over time among male recruits. No significant links were found between cumulative fireground exposures and PFAS concentrations. CONCLUSIONS: Serum PFAS concentrations were not increased in incumbent firefighters compared with recruits and were not associated with cumulative fireground exposures.
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Ácidos Alcanossulfônicos , Poluentes Ambientais , Bombeiros , Fluorocarbonos , Humanos , Masculino , Modelos Lineares , Coleta de DadosRESUMO
BACKGROUND: Noninvasive respiratory support (NRS) is increasingly used to support patients with acute respiratory failure. However, noninvasive support failure may worsen outcomes compared to primary support with invasive mechanical ventilation. Therefore, there is a need to identify patients where NRS is failing so that treatment can be reassessed and adjusted. The objective of this study was to develop and evaluate 3 recurrent neural network (RNN) models to predict NRS failure. METHODS: This was a cross-sectional observational study to evaluate the ability of deep RNN models (long short-term memory [LSTM], gated recurrent unit [GRU]), and GRU with trainable decay) to predict failure of NRS. Data were extracted from electronic health records from all adult (≥ 18 y) patient records requiring any type of oxygen therapy or mechanical ventilation between November 1, 2013-September 30, 2020, across 46 ICUs in the Southwest United States in a single health care network. Input variables for each model included serum chloride, creatinine, albumin, breathing frequency, heart rate, SpO2 , FIO2 , arterial oxygen saturation (SaO2 ), and 2 measurements each (point-of-care and laboratory measurement) of PaO2 and partial pressure of arterial oxygen from an arterial blood gas. RESULTS: Time series data from electronic health records were available for 22,075 subjects. The highest accuracy and area under the receiver operating characteristic curve were for the LSTM model (94.04% and 0.9636, respectively). Accurate predictions were made 12 h after ICU admission, and performance remained high well in advance of NRS failure. CONCLUSIONS: RNN models using routinely collected time series data can accurately predict NRS failure well before intubation. This lead time may provide an opportunity to intervene to optimize patient outcomes.
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Ventilação não Invasiva , Insuficiência Respiratória , Adulto , Humanos , Estudos Transversais , Oxigênio , Respiração Artificial , Oximetria , Oxigenoterapia/efeitos adversos , Insuficiência Respiratória/terapia , Insuficiência Respiratória/etiologiaRESUMO
Rationale: Noninvasive respiratory support modalities are common alternatives to mechanical ventilation for patients with early acute hypoxemic respiratory failure. These modalities include noninvasive positive pressure ventilation, using either continuous or bilevel positive airway pressure, and nasal high flow using a high flow nasal cannula system. However, outcomes data historically compare noninvasive respiratory support to conventional oxygen rather than to mechanical ventilation. Objectives: The goal of this study was to compare the outcomes of in-hospital death and alive discharge in patients with acute hypoxemic respiratory failure when treated initially with noninvasive respiratory support compared to patients treated initially with invasive mechanical ventilation. Methods: We used a validated phenotyping algorithm to classify all patients with eligible International Classification of Diseases codes at a large healthcare network between January 1, 2018 and December 31, 2019 into noninvasive respiratory support and invasive mechanical ventilation cohorts. The primary outcome was time-to-in-hospital death analyzed using an inverse probability of treatment weighted Cox model adjusted for potential confounders, with estimated cumulative incidence curves. Secondary outcomes included time-to-hospital discharge alive. A secondary analysis was conducted to examine potential differences between noninvasive positive pressure ventilation and nasal high flow. Results: During the study period, 3177 patients met inclusion criteria (40% invasive mechanical ventilation, 60% noninvasive respiratory support). Initial noninvasive respiratory support was not associated with a decreased hazard of in-hospital death (HR: 0.65, 95% CI: 0.35 - 1.2), but was associated with an increased hazard of discharge alive (HR: 2.26, 95% CI: 1.92 - 2.67). In-hospital death varied between the nasal high flow (HR 3.27, 95% CI: 1.43 - 7.45) and noninvasive positive pressure ventilation (HR 0.52, 95% CI 0.25 - 1.07), but both were associated with increased likelihood of discharge alive (nasal high flow HR 2.12, 95 CI: 1.25 - 3.57; noninvasive positive pressure ventilation HR 2.29, 95% CI: 1.92 - 2.74). Conclusion: These observational data from a large healthcare network show that noninvasive respiratory support is not associated with reduced hazards of in-hospital death but is associated with hospital discharge alive. There are also potential differences between the noninvasive respiratory support modalities.
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Acute respiratory failure is a common reason for ICU admission and imposes significant strain on patients and the healthcare system. Noninvasive positive-pressure ventilation and high-flow nasal oxygen are increasingly used as an alternative to invasive mechanical ventilation to treat acute respiratory failure. As such, there is a need to accurately cohort patients using large, routinely collected, clinical data to better understand utilization patterns and patient outcomes. The primary objective of this retrospective observational study was to externally validate our computable phenotyping algorithm for patients with acute respiratory failure requiring various sequences of respiratory support in real-world data from a large healthcare delivery network. DESIGN: This is a cross-sectional observational study to validate our algorithm for phenotyping acute respiratory patients by method of respiratory support. We randomly selected 5% (n = 4,319) from each phenotype for manual validation. We calculated the algorithm performance and generated summary statistics for each phenotype and a priori defined clinical subgroups. SETTING: Data were extracted from a clinical data warehouse containing electronic health record data from 46 ICUs in the southwest United States. PATIENTS: All adult (≥ 18 yr) patient records requiring any type of oxygen therapy or mechanical ventilation between November 1, 2013, and September 30, 2020, were extracted for the study. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Micro- and macroaveraged multiclass specificities of the algorithm were 0.902 and 0.896, respectively. Sensitivity and specificity of phenotypes individually were greater than 0.90 for all phenotypes except for those patients extubated from invasive to noninvasive ventilation. We successfully created clinical subgroups of common illnesses requiring ventilatory support and provide high-level comparison of outcomes. CONCLUSIONS: The electronic phenotyping algorithm is robust and provides a necessary tool for retrospective research for characterizing patients with acute respiratory failure across modalities of respiratory support.
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Purpose: The goal of this study was to compare noninvasive respiratory support to invasive mechanical ventilation as the initial respiratory support in COVID-19 patients with acute hypoxemic respiratory failure. Methods: All patients admitted to a large healthcare network with acute hypoxemic respiratory failure associated with COVID-19 and requiring respiratory support were eligible for inclusion. We compared patients treated initially with noninvasive respiratory support (noninvasive positive pressure ventilation by facemask or high flow nasal oxygen) with patients treated initially with invasive mechanical ventilation. The primary outcome was time-to-in-hospital death analyzed using an inverse probability of treatment weighted Cox model adjusted for potential confounders. Secondary outcomes included unweighted and weighted assessments of mortality, lengths-of-stay (intensive care unit and hospital) and time-to-intubation. Results: Over the study period, 2354 patients met inclusion criteria. Nearly half (47%) received invasive mechanical ventilation first and 53% received initial noninvasive respiratory support. There was an overall 38% in-hospital mortality (37% for invasive mechanical ventilation and 39% for noninvasive respiratory support). Initial noninvasive respiratory support was associated with an increased hazard of death compared to initial invasive mechanical ventilation (HR: 1.61, p < 0.0001, 95% CI: 1.33 - 1.94). However, patients on initial noninvasive respiratory support also experienced an increased hazard of leaving the hospital sooner, but the hazard ratio waned with time (HR: 0.97, p < 0.0001, 95% CI: 0.96 - 0.98). Conclusion: These data show that the COVID-19 patients with acute hypoxemic respiratory failure initially treated with noninvasive respiratory support had an increased hazard of in-hospital death.
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BACKGROUND: Self-reported hearing aid outcomes among older adults are variable and important to improve. The extent of the role of auditory processing in long-term hearing aid outcomes is not well understood. PURPOSE: To determine how auditory processing abilities are related to self-reported hearing aid satisfaction and benefit along with either aided audibility alone or exploratory factors suggested by previous literature. RESEARCH DESIGN: Descriptive analyses and multiple regression analyses of cross-sectional self-reported outcomes. STUDY SAMPLE: Adult participants, >60 years (n = 78), fitted with bilateral hearing aids to treat symmetric, mild to moderate sensorineural hearing loss. DATA COLLECTION AND ANALYSIS: Participants were recruited from a single audiology clinic to complete a series of questionnaires, behavioral assessments, and obtain data from their hearing aids, including real ear measures and data logging of hearing aid use. Multiple linear regressions were used to determine the amount of variance explained by predictive factors in self-reported hearing aid satisfaction and benefit. The primary predictive factors included gap detection threshold, spatial advantage score, dichotic difference score, and aided audibility. Exploratory factors included personality, self-efficacy, self-report of disability, and hearing aid use. All interpretations of statistical significance used p < 0.05. Effect sizes were determined using Cohen's f 2 with a medium effect suggesting clinical relevance. RESULTS: Gap detection threshold was a statistically significant predictor in both primary regression models with a medium effect size for satisfaction and a small effect size for benefit. When additional exploratory factors were included in the regression models with auditory processing abilities, gap detection and self-efficacy were both significant predictors of hearing aid satisfaction with medium effect sizes, explaining 10 and 17% of the variance, respectively. There were no medium effect sizes found for other predictor variables in either the primary or exploratory hearing aid benefit models. Additional factors were statistically significant in the models, explaining a small amount of variance, but did not meet the medium effect size criterion. CONCLUSION: This study provides initial evidence supporting the incorporation of measures of gap detection ability and hearing aid self-efficacy into clinical practice for the interpretation of postfitting long-term hearing aid satisfaction.
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Auxiliares de Audição , Perda Auditiva , Idoso , Percepção Auditiva , Estudos Transversais , Humanos , Pessoa de Meia-Idade , AutorrelatoRESUMO
Polymeric ionogels, cross-linked gels swollen by ionic liquids (ILs), are useful vehicles for the release and storage of molecular solutes in separation, delivery, and other applications. Although rapid solute diffusion is often critical for performance, it remains challenging to predict diffusivities across multidimensional composition spaces. Recently, we showed that water (a neutral solute) diffuses through alkyl-methylimidazolium halide ILs by hopping between hydrogen bonding sites on relatively immobile cations. Here, we expand on this activated hopping mechanism in two significant ways. First, we demonstrate that water diffuses through poly(ethylene glycol)diacrylate ionogels via the same mechanism at a reduced rate. Second, we hypothesize that the activation energy barrier can be determined from relatively simple 1H NMR chemical shift measurements of the proton responsible for H-bonding. This relationship enables water's diffusivity in ionogels of this class to be predicted quantitatively, requiring only (1) the composition-dependent diffusivity and Arrhenius behavior of a single IL and (2) 1H NMR spectra of the ionogels of interest. High-throughput microfluidic Fabry-Perot interferometry measurements verify prediction accuracy across a broad formulation space (four ILs, 0 ≤ xH2O ≤ 0.7, 0 ≤ ÏPEGDA ≤ 0.66). The predictive model may expedite IL-material screening; moreover, it intimates a powerful connection between solute mobility and hydrogen bonding and suggests targets for rational design.