Tag: pubmed

J Magn Reson Imaging. 2021 Oct 1. doi: 10.1002/jmri.27938. Online ahead of print.

ABSTRACT

BACKGROUND: Under normal physiological conditions, the spin-lattice relaxation rate (R1) in blood is influenced by many factors, including hematocrit, field strength, and the paramagnetic effects of deoxyhemoglobin and dissolved oxygen. In addition, techniques such as oxygen-enhanced magnetic resonance imaging (MRI) require high fractions of inspired oxygen to induce hyperoxia, which complicates the R1 signal further. A quantitative model relating total blood oxygen content to R1 could help explain these effects.

PURPOSE: To propose and assess a general model to estimate the R1 of blood, accounting for hematocrit, SO₂ , PO₂ , and B0 under both normal physiological and hyperoxic conditions.

STUDY TYPE: Mathematical modeling.

POPULATION: One hundred and twenty-six published values of R1 from phantoms and animal models.

FIELD STRENGTH/SEQUENCE: 5-8.45 T.

ASSESSMENT: We propose a two-compartment nonlinear model to calculate R1 as a function of hematocrit, PO₂ , and B0. The Akaike Information Criterion (AIC) was used to select the best-performing model with the fewest parameters. A previous model of R1 as a function of hematocrit, SO₂ , and B0 has been proposed by Hales et al, and our work builds upon this work to make the model applicable under hyperoxic conditions (SO₂ > 0.99). Models were assessed using the AIC, mean squared error (MSE), coefficient of determination (R² ), and Bland-Altman analysis. The effect of volume fraction constants $W_{\mathrm{RBC}}$ and $W_{\text{plasma}}$ was assessed by the SD of resulting R1. The range of the model was determined by the maximum and minimum B0, hematocrit, SO₂ , and PO₂ of the literature data points.

STATISTICAL TESTS: Bland-Altman, AIC, MSE, coefficient of determination (R² ), SD.

RESULTS: The model estimates agreed well with the literature values of R1 of blood (R² = 0.93, MSE = 0.0013 s^-2 ), and its performance was consistent across the range of parameters: B0 = 1.5-8.45 T, SO₂ = 0.40-1, PO₂ = 30-700 mmHg.

DATA CONCLUSION: Using the results from this model, we have quantified and explained the contradictory decrease in R1 reported in oxygen-enhanced MRI and oxygen-delivery experiments.

LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY: Stage 1.

PMID:34596290 | DOI:10.1002/jmri.27938

Stat Med. 2021 Oct 1. doi: 10.1002/sim.9211. Online ahead of print.

ABSTRACT

Post-GWAS analysis, in many cases, focuses on fine-mapping targeted genetic regions discovered at GWAS-stage; that is, the aim is to pinpoint potential causal variants and susceptibility genes for complex traits and disease outcomes using next-generation sequencing (NGS) technologies. Large-scale GWAS cohorts are necessary to identify target regions given the typically modest genetic effect sizes. In this context, two-phase sampling design and analysis is a cost-reduction technique that utilizes data collected during phase 1 GWAS to select an informative subsample for phase 2 sequencing. The main goal is to make inference for genetic variants measured via NGS by efficiently combining data from phases 1 and 2. We propose two approaches for selecting a phase 2 design under a budget constraint. The first method identifies sampling fractions that select a phase 2 design yielding an asymptotic variance covariance matrix with certain optimal characteristics, for example, smallest trace, via Lagrange multipliers (LM). The second relies on a genetic algorithm (GA) with a defined fitness function to identify exactly a phase 2 subsample. We perform comprehensive simulation studies to evaluate the empirical properties of the proposed designs for a genetic association study of a quantitative trait. We compare our methods against two ranked designs: residual-dependent sampling and a recently identified optimal design. Our findings demonstrate that the proposed designs, GA in particular, can render competitive power in combined phase 1 and 2 analysis compared with alternative designs while preserving type 1 error control. These results are especially evident under the more practical scenario where design values need to be defined a priori and are subject to misspecification. We illustrate the proposed methods in a study of triglyceride levels in the North Finland Birth Cohort of 1966. R code to reproduce our results is available at github.com/egosv/TwoPhase_postGWAS.

PMID:34596256 | DOI:10.1002/sim.9211

Clin Exp Pharmacol Physiol. 2021 Oct 1. doi: 10.1111/1440-1681.13597. Online ahead of print.

ABSTRACT

The aim of this prospective study was to construct a new pharmacokinetic model of vancomycin for target-concentration controlled infusion (TCI). As the first loading dose, 25 mg/kg of vancomycin was administered during 60-90 min. Arterial blood samples were obtained at pre-set intervals to measure the serum concentrations of vancomycin. Population pharmacokinetic analysis was performed using the NONMEM software (ICON Development Solutions, Dublin, Ireland). In total, 197 serum concentration measurements from 22 patients were used to characterize the pharmacokinetics of vancomycin. A three-compartment mammillary model best described the pharmacokinetics of vancomycin in critically ill patients. The ideal body weight was a significant covariate for the central and slow peripheral volume of distribution. The weight and age converted to categorical variables at a cut-off of 65 years were a significant covariate for the clearance. Based on the results of stochastic simulation, the TCI method maintained the therapeutic concentration range for the longest duration. In addition, assuming that vancomycin was administered by the TCI method for 7 days, the dose was reduced by about 15% compared with the standard administration methods. The daily area under the curve values were maintained between 500 mg·h/L and 600 mg·h/L. TCI has the potential to become a new infusion method for patient-tailored dosing in critically ill patients. To administer vancomycin via TCI in clinical practice, the newly constructed pharmacokinetic model should undergo proper external validation.

PMID:34596258 | DOI:10.1111/1440-1681.13597

Clin Infect Dis. 2021 Oct 1:ciab875. doi: 10.1093/cid/ciab875. Online ahead of print.

ABSTRACT

BACKGROUND: Remdesivir (RDV) improved clinical outcomes among hospitalized COVID-19 patients in randomized trials, but data from clinical practice are limited.

METHODS: We examined survival outcomes for US patients hospitalized with COVID-19 between Aug-Nov 2020 and treated with RDV within two-days of hospitalization vs. those not receiving RDV during their hospitalization using the Premier Healthcare Database. Preferential within-hospital propensity score matching with replacement was used. Additionally, patients were also matched on baseline oxygenation level (no supplemental oxygen charges (NSO), low-flow oxygen (LFO), high-flow oxygen/non-invasive ventilation (HFO/NIV) and invasive mechanical ventilation/ECMO (IMV/ECMO) and two-month admission window and excluded if discharged within 3-days of admission (to exclude anticipated discharges/transfers within 72-hrs consistent with ACTT-1 study). Cox Proportional Hazards models were used to assess time to 14-/28-day mortality overall and for patients on NSO, LFO, HFO/NIV and IMV/ECMO.

RESULTS: 28,855 RDV patients were matched to 16,687 unique non-RDV patients. Overall, 10.6% and 15.4% RDV patients died within 14- and 28-days, respectively compared with 15.4% and 19.1% non-RDV patients. Overall, RDV was associated with a reduction in mortality at 14-days (HR[95% CI]: 0.76[0.70-0.83]) and 28-days (0.89[0.82-0.96]). This mortality benefit was also seen for NSO, LFO and IMV/ECMO at 14-days (NSO:0.69[0.57-0.83], LFO:0.68[0.80-0.77], IMV/ECMO:0.70[0.58-0.84]) and 28-days (NSO:0.80[0.68-0.94], LFO:0.77[0.68-0.86], IMV/ECMO:0.81[0.69-0.94]). Additionally, HFO/NIV RDV group had a lower risk of mortality at 14-days (0.81[0.70-0.93]) but no statistical significance at 28-days.

CONCLUSIONS: RDV initiated upon hospital admission was associated with improved survival among COVID-19 patients. Our findings complement ACTT-1 and support RDV as a foundational treatment for hospitalized COVID-19 patients.

PMID:34596223 | DOI:10.1093/cid/ciab875

J Dermatol. 2021 Oct 1. doi: 10.1111/1346-8138.16175. Online ahead of print.

ABSTRACT

A decrease in the ceramide content of the stratum corneum is known to cause dry and barrier-disrupted skin. In this literature review, the clinical usefulness of preparations containing natural or synthetic ceramides for water retention and barrier functions was evaluated. The PubMed, Cochrane Library, and Igaku Chuo Zasshi databases were searched using keywords such as “ceramide”, “skincare products”, “barrier + hydration + moisture + skin”, and “randomized trial”. All database searches were conducted in February 2019. Forty-one reports were selected based on the following criterion: comparative control studies that evaluated the effects of ceramide-containing formulations based on statistical evidence. Among the 41 reports, 12 were selected using the patient, intervention, comparison, and outcome approach. These 12 reports showed that external ceramide-containing preparations can improve dry skin and barrier function in patients with atopic dermatitis. However, a double-blinded comparative study with a large sample size is warranted for appropriate clinical use.

PMID:34596254 | DOI:10.1111/1346-8138.16175

Am J Clin Pathol. 2021 Oct 1:aqab144. doi: 10.1093/ajcp/aqab144. Online ahead of print.

ABSTRACT

OBJECTIVES: To develop a structured, introductory curriculum in scientific writing and publishing for residents in anatomic pathology.

METHODS: We assessed the need for this curriculum by using an online questionnaire sent to anatomic pathology residents in our program and tailored content to address areas of least familiarity. The curriculum consisted of 4 virtual lectures delivered by select experts in the field. Curriculum evaluation was assessed through a postcurriculum questionnaire.

RESULTS: In total, 27 of 31 (87%) residents responded to the initial questionnaire. The major educational need was identified in the following topics: “responsibilities of a corresponding author”; “selecting a journal for publication”; “editor’s approach to evaluating a manuscript”; “correspondence with editors and reviewers”; and “open access, cost and increasing exposure to manuscript.” Eight residents participated in at least 3 of 4 lectures and completed the pre- and postcurriculum survey. The postcurriculum survey demonstrated statistically significant interval increases in familiarity with 7 of 18 topics, and the leading increases were noted in topics of most significant educational need.

CONCLUSIONS: Development of novel curricula is vital to the ever-changing landscape of pathology resident education. This study proposes a generalizable algorithmic approach to assessing new areas of educational need and effectively addressing them through targeted curricula.

PMID:34596207 | DOI:10.1093/ajcp/aqab144

Demography. 2021 Oct 1:9530075. doi: 10.1215/00703370-9530075. Online ahead of print.

ABSTRACT

The accurate measurement of poverty is essential for the development of effective poverty policy. Unfortunately, approaches that use poverty rates to assess the causes and consequences of poverty do not fully capture the components of change in the poverty population because changes in the conventional poverty rate can occur owing to processes of natural increase, migration, or transitions in and out of poverty. This article presents an accounting framework for changes in poverty within and between places. The framework, termed the poverty balancing equation, generates a series of summary statistics that can be used in place of the conventional poverty rate in future research. The approach is demonstrated using the 2014 panel of the Survey of Income and Program Participation to generate state-level estimates of the poverty components of change for three states in the American South between January and December of 2013. Results show that even when poverty rates remain constant, there is significant dynamism within poor and nonpoor populations. By applying this approach, either completely or in part, researchers can provide more specific and actionable evidence for poverty alleviation policy.

PMID:34596211 | DOI:10.1215/00703370-9530075

Med Pr. 2021 Sep 16:139129. doi: 10.13075/mp.5893.01085. Online ahead of print.

ABSTRACT

BACKGROUND: The aim of the study was to assess the correct insertion of earplugs in the ear canal by people with different knowledge regarding this matter. The use of hearing protectors leads to a reduction in the risk of hearing loss, which is part of environmental engineering.

MATERIAL AND METHODS: Measurements of sound attenuation by earplugs were carried out with the participation of 21 people with no experience in the use of earplugs. The measurements were repeated until the subjects had read the instructions for the use of earplugs, and then after the subjects had been trained in the correct insertion of earplugs in the ear canal. The tests were carried out using a newly developed portable device for quick measurements of sound attenuation.

RESULTS: Familiarizing the subjects with the instructions for use resulted in a sound attenuation value being 6.7 and 3.3 dB higher, at 250 and 4000 Hz, respectively, compared to the measurement when the subjects inserted earplugs in the ear canal without any guidance. An even greater increase in attenuation was observed when the subjects were trained to insert earplugs, at 9.2 dB (250 Hz) and 5.4 dB (4000 Hz), respectively. In most cases, the changes in attenuation as a result of providing guidance were statistically significant.

CONCLUSIONS: Persons who have no experience in using earplugs have significant problems with their correct insertion. Reading the instructions for use does not guarantee that earplugs will be inserted correctly. Only the training showing how to insert the earplugs correctly results in people being able to do it correctly in most cases. Med Pr. 2021;72(5).

PMID:34596171 | DOI:10.13075/mp.5893.01085

Environ Sci Process Impacts. 2021 Oct 1. doi: 10.1039/d1em00202c. Online ahead of print.

ABSTRACT

Indoor flooding is a leading contributor to indoor dampness and the associated mold infestations in the coastal United States. Whether the prevalent mold genera that infest the coastal flood-prone buildings are different from those not flood-prone is unknown. In the current case study of 28 mold-infested buildings across the U.S. east coast, we surprisingly noted a trend of higher prevalence of indoor Aspergillus and Penicillium genera (denoted here as Asp-Pen) in buildings with previous flooding history. Hence, we sought to determine the possibility of a potential statistically significant association between indoor Asp-Pen prevalence and three building-related variables: (i) indoor flooding history, (ii) geographical location, and (iii) the building’s use (residential versus non-residential). Culturable spores and hyphal fragments in indoor air were collected using the settle-plate method, and corresponding genera were confirmed using phylogenetic analysis of their ITS sequence (the fungal barcode). Analysis of variance (ANOVA) using Generalized linear model procedure (GLM) showed that Asp-Pen prevalence is significantly associated with indoor flooding as well as coastal proximity. To address the small sample size, a multivariate decision tree analysis was conducted, which ranked indoor flooding history as the strongest determinant of Asp-Pen prevalence, followed by geographical location and the building’s use.

PMID:34596193 | DOI:10.1039/d1em00202c

Medicine (Baltimore). 2021 Oct 1;100(39):e27417. doi: 10.1097/MD.0000000000027417.

ABSTRACT

This study evaluated the clinical implications of hepatitis B surface antigen quantification (qHBs Ag) in chronic hepatitis B (CHB) patients treated with entecavir (ETV) or tenofovir disoproxil fumarate (TDF) and identified the association between qHBs Ag and the risk of hepatocellular carcinoma (HCC) in these patients.Between January 2007 and December 2018, the qHBs Ag and clinical data of 183 CHB patients who initially received ETV (n = 45, 24.6%) or TDF (n = 138, 75.4%) were analyzed.The mean follow-up period of the 183 CHB patients was 45.3 months, of which 59 (32.2%) patients showed a reduction in qHBs Ag by >50% after 1 year of antiviral treatment (ETV or TDF). The HCC development (P = .179) or qHBs Ag reduction (P = .524) were similar in the ETV and TDF groups. Patients with a ≥50% decrease in qHBs Ag had a significantly lower incidence of HCC or decompensated cirrhosis complications (P = .005). Multivariate analysis showed that a >50% reduction of qHBs Ag (hazard ratio 0.085, P = .018) and the presence of cirrhosis (hazard ratio 3.32, P = .016) were independent factors predicting the development of HCC.Patients whose qHBs Ag value decreased >50% at 1 year after antiviral treatment for CHB showed a significant decrease in HCC or decompensated cirrhosis events. A reduction in qHBs Ag could be used as a predictive factor of HCC development or critical complications in CHB patients treated with TDF or ETV.

PMID:34596169 | DOI:10.1097/MD.0000000000027417