bluuebunny/crossref_metadata_2025 huggingface dataset:
Disease Severity and Perinatal Outcomes of Pregnant Patients With Coronavirus Disease 2019 (COVID-19)
Authors: Metz Torri D. , Clifton Rebecca G. , Hughes Brenna L. , Sandoval Grecio , Saade George R. , Grobman William A. , Manuck Tracy A. , Miodovnik Menachem , Sowles Amber , Clark Kelly , Gyamfi-Bannerman Cynthia , Mendez-Figueroa Hector , Sehdev Harish M. , Rouse Dwight J. , Tita Alan T.N. , Bailit Jennifer , Costantine Maged M. , Simhan Hyagriv N. , Macones George A. ,   for the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Maternal-Fetal Medicine Units (MFMU) Network
Published: February 2021

OBJECTIVE:

To describe coronavirus disease 2019 (COVID-19) severity in pregnant patients and evaluate the association between disease severity and perinatal outcomes.

METHODS:

We conducted an observational cohort study of all pregnant patients with a singleton gestation and a positive test result for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) who delivered at 1 of 33 U.S. hospitals in 14 states from March 1 to July 31, 2020. Disease severity was classified by National Institutes of Health criteria. Maternal, fetal, and neonatal outcomes were abstracted by centrally trained and certified perinatal research staff. We evaluated trends in maternal characteristics and outcomes across COVID-19 severity classes and associations between severity and outcomes by multivariable modeling.

RESULTS:

A total of 1,219 patients were included: 47% asymptomatic, 27% mild, 14% moderate, 8% severe, 4% critical. Overall, 53% were Hispanic; there was no trend in race–ethnicity distribution by disease severity. Those with more severe illness had older mean age, higher median body mass index, and pre-existing medical comorbidities. Four maternal deaths (0.3%) were attributed to COVID-19. Frequency of perinatal death or a positive neonatal SARS-CoV-2 test result did not differ by severity. Adverse perinatal outcomes were more frequent among patients with more severe illness, including 6% (95% CI 2–11%) incidence of venous thromboembolism among those with severe–critical illness compared with 0.2% in mild–moderate and 0% in asymptomatic (P<.001 for trend across severity). In adjusted analyses, severe–critical COVID-19 was associated with increased risk of cesarean birth (59.6% vs 34.0%, adjusted relative risk [aRR] 1.57, 95% CI 1.30–1.90), hypertensive disorders of pregnancy (40.4% vs 18.8%, aRR 1.61, 95% CI 1.18–2.20), and preterm birth (41.8% vs 11.9%, aRR 3.53, 95% CI 2.42–5.14) compared with asymptomatic patients. Mild–moderate COVID-19 was not associated with adverse perinatal outcomes compared with asymptomatic patients.

CONCLUSION:

Compared with pregnant patients with SARS-CoV-2 infection without symptoms, those with severe–critical COVID-19, but not those with mild–moderate COVID-19, were at increased risk of perinatal complications.
Effect of Age at Cochlear Implantation in Educational Placement and Peer Relationships
Authors: Choo Oak-Sung , Kim Hantai , Kim You-Jeong , Roh Jimin , Jang Jeong Hun , Park Hun Yi , Choung Yun-Hoon
Published: February 2021

Objectives:

The education and school life of children who have undergone cochlear implantation (CI) is very important and should be monitored continuously. This study assessed auditory performance in children with cochlear implants over time, along with educational placement and peer relationship, and compared the results based on the age at CI and the presence of additional disabilities.

Design:

In total, 77 children who had undergone CI at the Hearing Center in Ajou University Hospital at less than 10 years old and who were presently attending school or had already graduated from school within 3 years were enrolled in this study. All children had congenital bilateral severe or profound hearing loss at the diagnosis. They were classified based on the age at which they received CI: the “early-implanted group,” younger than 3.5 years (n = 38), and the “late-implanted group,” between 3.5 and 10 years old (n = 39).

Results:

The early-implanted group had worse short-term auditory performance than the late group, but after 2 years of the implant use, auditory performance was similar in both groups. The early and late groups did not differ significantly in terms of the proportions of children who were enrolled in a regular school (94.7% and 89.7%, respectively). However, the early-implanted group had a larger proportion of children who were enrolled in a regular school without additional needs (73.0%), compared with the late group (48.6%) (p = .034). Children with multiple disabilities showed poorer performance (word score of 57.7% and sentence score of 44.7%) than children with hearing disability only (91.8% and 87.2%, respectively), which affected full-time enrollment in regular schools. With regard to peer relationships, 19.0% of children in the early-implanted group required close observation and assistance, and 9.5% even required help and counseling. Children who underwent early CI had a high tendency toward social restraint, apathy, and over-commitment. No correlations were observed between audiological factors and the aspects of peer relationships assessed in this study.

Conclusions:

Early CI and the absence of other disabilities were the two main factors that increased the likelihood of full-time enrollment in mainstream classes at regular schools. Nevertheless, many children who underwent earlier CI still encountered difficulties in peer relationships.
Outcomes of a Minimally Invasive Approach for Congenital Vertical Talus With a Comparison Between the Idiopathic and Syndromic Feet
Authors: Hafez Mohamed , Davis Naomi
Published: February 2021

Background:

Congenital vertical talus (CVT) is a rare congenital foot disorder. Approximately half of the affected children have associated neuromuscular syndromes which may further complicate the treatment. The traditional treatment involved extensive soft tissue and bony reconstructions. The minimally invasive method (Dobbs method/reverse Ponseti) has changed the treatment of CVT. There is significant variation of the reported outcome of this method in the current literature. In this study we report the outcome of this minimally invasive technique for treatment of CVT and compare the results of treatment in syndromic and idiopathic patients.

Methods:

Idiopathic and syndromic patients treated from CVT with minimally invasive method from 2006 till 2016 were included in this retrospective study. We reviewed the patients’ notes, radiographs and collected parents reported outcome questionnaire (Roye score) in addition to clinical examination to comprehensively report the treatment outcome.

Results:

A total of 21 patients 30 feet were included in this study. The average age of commencing treatment was 6 months (1 to 17 mo). The mean follow-up was 6.5 years (1 to 11 y). Correction of the deformities and abnormal angles were achieved in all feet. Five of the 17 syndromic feet had recurrence while no recurrence was reported in any if the 13 idiopathic feet. At the time of the index procedure no supplementary procedures were required. The average arc of motion for foot ankle dorsiflexion and plantar flexion was 30 degrees. Patients with idiopathic CVT had a mean the Roye score of 11 while syndromic patients had a mean score of 22.

Conclusion:

The minimally invasive method is a valuable option for treatment of CVT. Idiopathic patients had no recurrence and better functional scores compared syndromic patients. There was no requirement for supplementary procedures such as tibialis anterior transfer or anterolateral release at the time of the initial surgery.

Level of Evidence:

Level IV—case series.
The Use of Modified Ollier Approach and Structural Allograft for Fixation of Intra-articular Calcaneal Fractures
Authors: Tay Guan Tzu , Ng Julia Poh Hwee , Ng Jordan Wei Peng , Lee Marcus Josef Jian Rong , Foo Gen Lin , Wee James
Published: February 2021

We describe the combination of an Ollier approach and use of a structural allograft, for displaced intra-articular calcaneal fractures, that minimizes soft issue complications known to plague such fractures. The soft tissue envelope around the fracture fragments is maintained, facilitating fracture reduction. The mini-open incision is positioned such that critical elements of the subtalar joint are adequately visualized throughout the reduction and fixation. We have used this procedure for all grades of Sanders intra-articular fractures with no significant short-term complications thus far.

Level of Evidence: Diagnostic Level V—Expert opinion. See Instructions for Authors for a complete description of levels of evidence.
Development and internal validation of China mortality prediction model in trauma based on ICD-10-CM lexicon: CMPMIT-ICD10
Authors: Wang Yan-Hua , Wang Tian-Bing , Zhang Zi-Xiao , Liu Hui-Xin , Xu Ting-Min , Wang Chu , Jiang Bao-Guo
Published: February 2021

Background:

Models to predict mortality in trauma play an important role in outcome prediction and severity adjustment, which informs trauma quality assessment and research. Hospitals in China typically use the International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) to describe injury. However, there is no suitable prediction model for China. This study attempts to develop a new mortality prediction model based on the ICD-10-CM lexicon and a Chinese database.

Methods:

This retrospective study extracted the data of all trauma patients admitted to the Beijing Red Cross Emergency Center, from January 2012 to July 2018 (n = 40,205). We used relevant predictive variables to establish a prediction model following logistic regression analysis. The performance of the model was assessed based on discrimination and calibration. The bootstrapping method was used for internal validation and adjustment of model performance.

Results:

Sex, age, new region-severity codes, comorbidities, traumatic shock, and coma were finally included in the new model as key predictors of mortality. Among them, coma and traumatic shock had the highest scores in the model. The discrimination and calibration of this model were significant, and the internal validation performance was good. The values of the area under the curve and Brier score for the new model were 0.9640 and 0.0177, respectively; after adjustment of the bootstrapping method, they were 0.9630 and 0.0178, respectively.

Conclusions:

The new model (China Mortality Prediction Model in Trauma based on the ICD-10-CM lexicon) showed great discrimination and calibration, and performed well in internal validation; it should be further verified externally.
Preeclampsia: A Review of Early Predictors
Authors: Abbas Riwa A. , Ghulmiyyah Labib , Hobeika Elie , Usta Ihab M. , Mirza Fadi , Nassar Anwar H.
Published: February 2021

Preeclampsia is a progressive, multi-system disorder of pregnancy associated with morbidity and mortality on both the mother and the fetus. Currently, research is directed at identifying early biomarkers of preeclampsia in order to predict its occurrence. This is important because it helps understand the pathophysiology of the disease, and thus, promises new treatment modalities. Although a clear understanding of the pathogenesis of PE remains elusive, the currently most accepted theory suggests a two-stage process. The first stage results in inadequate remodeling of the spiral arteries and leads to the second stage, whereby the clinical features of the syndrome are featured. In this review, we summarize the modalities that have been studies so far to predict preeclampsia. The use of uterine artery Doppler and several other biomarkers such as vitamin D, soluble fms-like tyrosine kinase 1/placental growth factor (sFLT1/PlGF) ratio, soluble endoglin, and a subset of T-lymphocytes has shown promising results. We are still at early stages in this advance, and no clear recommendations have been made about their clinical use to date. Further studies are still needed to improve screening strategies and evaluate the cost-effectiveness of any intervention.
The Gut Microbiome During Pregnancy
Authors: Jiang Guoqing , Zhou Zhiyi , Li Xiaojuan , Qian Yuan , Wang Kunhua
Published: February 2021

Gut microbiota is symbiotic and interdependent with human body. Intestinal probiotics are colonized in the human gastrointestinal tract, which can improve the host intestinal microenvironment and enhance the intestinal function and immune function of the human body. A small number of opportunistic pathogens exist in the intestinal tract. Once the number of pathogens exceeds the threshold of intestinal tolerance, the intestinal micro-ecological balance can be destroyed, and various diseases may thus develop. Pregnancy is a special status with different physiologic changing stages. In the meanwhile, alterations in the gut microbiome populations occur, which can promote the differentiation, development, and maturation of fetal organs by affecting maternal metabolism. Compared with normal pregnant women, great changes in the gastrointestinal function and gut microbiome may take place in pregnant women with pregnancy-related complications, in which these changes include the number, species, and intestinal translocation. The composition of the maternal gut microbiome could contribute to pregnancy and obstetric outcomes, and long-term health of mother and child. The relationships of pregnancy to gut microbiome have attracted an increasing attention in recent years. This article will provide a summary review of the research studies of gut microbiome in normal pregnant women versus abnormal pregnancy women with complications.
Perinatal Management and Outcomes of Pregnancy Following Sheehan Syndrome: A Case Report and Literature Review
Authors: Zhan Yongchi , Xu Tingting , Wang Xiaodong
Published: February 2021

Pregnancy is rare and difficult in Sheehan syndrome patients. With the help of assisted reproductive technology, the patients even with panhypopituitarism can get pregnant again. Moreover, women with hypopituitarism have increased risk of pregnancy complications. Here we report a patient who suffered acute and severe Sheehan syndrome with panhypopituitarism and central diabetes insipidus got pregnant again by in vitro fertilization and embryo transfer. A regular and careful antenatal care was given by the cooperation between obstetricians and endocrinologists. Finally, she delivered a healthy female baby at 37+6 weeks of gestation with Apgar scores of 10 and 10 at 1 and 5 minutes, respectively. The patient and her baby were doing well at postpartum follow-up. The related articles were also reviewed. This case report is aimed to help clinical practitioners to make better decisions on the management of Sheehan syndrome or other type of hypopituitarism during pregnancy.
Can We Predict Individual Concentrations of Tacrolimus After Liver Transplantation? Application and Tweaking of a Published Population Pharmacokinetic Model in Clinical Practice
Authors: Decrocq-Rudler Marie-Astrid , Chan Kwong Anna H-X. P. , Meunier Lucy , Fraisse Julien , Ursic-Bedoya José , Khier Sonia
Published: February 2021

Background:

Various population pharmacokinetic models have been developed to describe the pharmacokinetics of tacrolimus in adult liver transplantation. However, their extrapolated predictive performance remains unclear in clinical practice. The purpose of this study was to predict concentrations using a selected literature model and to improve these predictions by tweaking the model with a subset of the target population.

Methods:

A literature review was conducted to select an adequate population pharmacokinetic model (L). Pharmacokinetic data from therapeutic drug monitoring of tacrolimus in liver-transplanted adults were retrospectively collected. A subset of these data (70%) was exploited to tweak the L-model using the $PRIOR subroutine of the NONMEM software, with 2 strategies to weight the prior information: full informative (F) and optimized (O). An external evaluation was performed on the remaining data; bias and imprecision were evaluated for predictions a priori and Bayesian forecasting.

Results:

Seventy-nine patients (851 concentrations) were enrolled in the study. The predictive performance of L-model was insufficient for a priori predictions, whereas it was acceptable with Bayesian forecasting, from the third prediction (ie, with ≥2 previously observed concentrations), corresponding to 1 week after transplantation. Overall, the tweaked models showed a better predictive ability than the L-model. The bias of a priori predictions was −41% with the literature model versus −28.5% and −8.73% with tweaked F and O models, respectively. The imprecision was 45.4% with the literature model versus 38.0% and 39.2% with tweaked F and O models, respectively. For Bayesian predictions, whatever the forecasting state, the tweaked models tend to obtain better results.

Conclusions:

A pharmacokinetic model can be used, and to improve the predictive performance, tweaking the literature model with the $PRIOR approach allows to obtain better predictions.
Therapeutic Drug Monitoring of Psychotropics as a Diagnostic Tool for CYP2D6 Poor Metabolizer Phenotype
Authors: Ganesh Soraya V. , Beunk Lianne , Nikolik Bojan , van der Weide Jan , Bet Pierre M.
Published: February 2021

Background:

Interpatient variability in cytochrome P450 2D6 (CYP2D6) enzyme activity alters the serum concentrations of most psychotropics, which often have narrow therapeutic indices. Therefore, preemptive knowledge of CYP2D6 activity is desired. However, accessible indicators for deficient CYP2D6 activity are necessary because genotyping all patients prescribed CYP2D6 metabolized drugs is often not feasible or cost-effective.

Methods:

In this study, the predictive value of the ratio between a CYP2D6 substrate and its metabolite, known as the metabolic ratio (MR), the dose-corrected serum concentration of substrate (CDR), and the dose-corrected sum concentration of substrate and metabolite (Sum CDR) of venlafaxine, risperidone, aripiprazole, and nortriptyline were determined to predict the CYP2D6 poor metabolizer (PM) phenotype. The area-under-the-receiver operator characteristic curve, as well as the sensitivity, specificity, and positive and negative predictive values of the optimal thresholds, were calculated.

Results:

Although the MR, CDR, and Sum CDR all predicted the CYP2D6 PM phenotype, the predictive value of the MR was most robust for venlafaxine and aripiprazole, and the Sum CDR was inferior for all 3 psychotropics. MRs of venlafaxine, risperidone, and aripiprazole, and CDR of nortriptyline showed an area-under-the-receiver operator characteristics (95% confidence interval) of 97.2% (94.7%–99.6%), 93.0% (88.8%–97.2%), 97.8% (95.4%–100.0%), and 85.6% (78.0%–93.1%), respectively. Thresholds of the log(MR) of ≥0.1 for venlafaxine, ≥0.0 for risperidone, and ≥1.5 for aripiprazole, and log(CDR) ≥0.5 for nortriptyline produced >92% sensitivity and >64% specificity.

Conclusions:

If therapeutic drug monitoring is available, the thresholds presented here could serve as a diagnostic tool for the CYP2D6 PM phenotype of psychiatric patients prescribed the aforementioned psychotropic medications.
A Broad Range High-Throughput Assay for Lenvatinib Using Ultra-High Performance Liquid Chromatography Coupled to Tandem Mass Spectrometry With Clinical Application in Patients With Hepatocellular Carcinoma
Authors: Sueshige Yoshio , Shiraiwa Ken , Honda Koichi , Tanaka Ryota , Saito Tomoko , Tokoro Masanori , Iwao Masao , Endo Mizuki , Arakawa Mie , Tatsuta Ryosuke , Seike Masataka , Murakami Kazunari , Itoh Hiroki
Published: February 2021

Background:

Lenvatinib is increasingly being selected as the first-line treatment for unresectable hepatocellular carcinoma (HCC) based on the results of the REFLECT trial. However, early discontinuation of lenvatinib because of adverse effects is a frequent occurrence. Hence, lenvatinib is a difficult drug for use in the clinical setting. One of the causes is that the dose of lenvatinib is mainly determined by body weight alone, despite high interindividual variability. To overcome this problem, a dosing regimen of lenvatinib based on a population pharmacokinetic (PPK) model for HCC patients is proposed. The aim of this study was to develop a high-throughput quantification method for lenvatinib using ultra-high performance liquid chromatography coupled to tandem mass spectrometry (UHPLC-MS/MS) that can be applied to a PPK analysis of HCC patients in the future.

Methods:

After a simple solid-phase extraction step using a 96-well plate, lenvatinib was analyzed by UHPLC-MS/MS in a positive electrospray ionization mode.

Results:

The novel method fulfilled the requirements of the US Food and Drug Administration guidance on bioanalytical method validation. The calibration curve was linear over the 0.2–1000 ng/mL concentration range. The average recovery rate was 98.63 ± 4.55% (mean ± SD). The precision was below 6.05%, and the accuracy was within 12.96% for all quality control levels. The matrix effect varied between 103.33% and 134.61%. This assay was successfully applied to the measurement of plasma concentrations in 6 HCC patients receiving lenvatinib.

Conclusions:

A novel high-throughput UHPLC-MS/MS assay for quantification of lenvatinib in human plasma was successfully developed. This method can be applied to PPK analysis for patients receiving lenvatinib in the clinical setting.
Therapeutic Drug Monitoring and Pharmacokinetic Analysis of Cyclosporine in a Pediatric Patient with Hemophagocytic Lymphohistiocytosis Complicated by Diabetes Insipidus: A Grand Round
Authors: Liang Yujian , Wu Zhaoyi , Zhao Liyan , Wu Jingjing , Chen Xiao , Tang Wen , Zeng Jiawei
Published: February 2021

Background:

Hemophagocytic lymphohistiocytosis (HLH) is a rare life-threatening disease. Initial therapy is based on etoposide, dexamethasone, and cyclosporine (CSA). The pharmacokinetics (PKs) of CSA and other drugs are sometimes altered in patients with HLH complicated by diabetes insipidus (DI) but the precise mechanisms remain unknown.

Methods:

In this study, the authors present a case of a 4-year-old boy with HLH complicated by DI. CSA concentrations were determined by enzyme multiplied immunoassay technique; noncompartmental PK analysis of the plasma concentration–time data was performed using PKSolver; and linear regression analysis was performed to determine linearity of relationship between urine output and C0 levels of CSA.

Results:

Although C0 values of CSA were lower than the target levels, the patient was successfully treated and a good clinical outcome was achieved. Linear regression analysis showed a strong negative correlation between urine output and the serum trough concentration (C0) of CSA, pharmacokinetic analysis showed the main PK parameters of CSA as follows: C0, 50.2 mcg/L; peak concentration (Cmax), 723.4 mcg/L; area under the curve0–24, 7478.2 mcg·h/L; clearance, 0.77 L/h/kg, elimination half-life, 5.3 hours, and volume of distribution, 6.0 L/kg.

Conclusions:

To the best of the authors' knowledge, this is the first report of the CSA PK profile in a patient with HLH complicated by DI. The authors suppose that a large fluid output and input leads to extensive CSA distribution. These results suggest that the monitoring of the Cmax and area under the curve of CSA might be more clinically and pharmacokinetically significant than that of C0 in patients with HLH complicated by DI. This case highlights the importance of therapeutic drug monitoring and demonstrates PK parameters of CSA in a pediatric patient with HLH complicated by DI.
A Population Pharmacokinetic Modeling and Simulation Study of Posaconazole Oral Suspension in Immunocompromised Pediatric Patients: A Short Communication
Authors: Elkayal Omar , Spriet Isabel , Uyttebroeck Anne , Colita Anca , Annaert Pieter , Allegaert Karel , Smits Anne , Van Daele Ruth , Dreesen Erwin
Published: February 2021

Background:

Posaconazole oral suspension emerged as a promising candidate for prophylaxis of invasive fungal infections in immunocompromised children. Its pharmacodynamic advantages include a broad-spectrum activity and a favorable safety profile; however, they are overshadowed by its large pharmacokinetic (PK) variability, which might cause subtherapeutic exposure. The aim of this study was to develop a population (pop) PK model based on rich sampling data to better understand the PK of posaconazole oral suspension in pediatric patients.

Methods:

Data were obtained from a prospective interventional study involving hospitalized pediatric patients with a hematologic malignancy and prophylactically treated with posaconazole oral suspension. After constructing the popPK model, the probability of target attainment (PTA; 100% T ≥ 0.7 mg/L) for prophylaxis under fixed, body weight-based, and body surface area-based dosing was evaluated using Monte Carlo simulation.

Results:

Fourteen patients contributed 112 posaconazole plasma concentrations. The PK of posaconazole was adequately described by a 1-compartment model with lag time 2.71 hours [13%]; nonlinear bioavailability ED50 99.1 mg/m2 (fixed); first-order absorption rate constant 0.325 hour−1 [27%]; apparent volume of distribution 1150 L [34%]; and apparent clearance 15.4 L/h [24%] (∼70-kg individual). The bioavailability decreased in the presence of diarrhea and co-treatment with a proton pump inhibitor (PPI). The unexplained interindividual variability in posaconazole PK remained large. The PTA was <85%, irrespective of the simulated dosing strategy. Patients without diarrhea and not administered a PPI had the highest PTA (85% under the fixed 300-mg dosing 4 times per day).

Conclusions:

Therapeutic drug monitoring is recommended during prophylactic posaconazole therapy in immunocompromised pediatric patients. Large-scale comparative studies are needed to characterize the PK variability between different posaconazole formulations in this cohort.
Is Attention-Deficit/Hyperactivity Disorder a Risk Syndrome for Parkinson’s Disease?
Authors: Baumeister Alan A.
Published: February 2021

Recent epidemiological evidence indicates that diagnosis of attention-deficit/hyperactivity disorder (ADHD) is associated with increased risk for diseases of the basal ganglia and cerebellum, including Parkinson’s disease (PD). The evidence reviewed here indicates that deficits in striatal dopamine are a shared component of the causal chains that produce these disorders. Neuropsychological studies of adult ADHD, prodromal PD, and early-stage PD reveal similar deficits in executive functions, memory, attention, and inhibition that are mediated by similar neural substrates. These and other findings are consistent with the possibility that ADHD may be part of the PD prodrome. The mechanisms that may mediate the association between PD and ADHD include neurotoxic effects of stimulants, other environmental exposures, and Lewy pathology. Understanding the nature of the association between PD and ADHD may provide insight into the etiology and pathogenesis of both disorders. The possible contribution of stimulants to this association may have important clinical and public health implications.
CORRELATION BETWEEN ATROPHY-TRACTION-NEOVASCULARIZATION GRADE FOR MYOPIC MACULOPATHY AND CLINICAL SEVERITY
Authors: Ruiz-Medrano Jorge , Flores-Moreno Ignacio , Ohno-Matsui Kyoko , Cheung Chui Ming Gemmy , Silva Rufino , Ruiz-Moreno José M.
Published: February 2021

Purpose:

To assess the reliability of the atrophy-traction-neovascularization (ATN) classification in patients with pathologic myopia (PM) and its correlation with best-corrected visual acuity (BCVA).

Methods:

Cross-sectional study. Hundred highly myopic eyes with a spherical equivalent of >−6.0 diopters or axial length of >26 mm and a total ATN score of ≥3 underwent a complete ophthalmological examination, including fundus photography and swept-source optical coherence tomography. Five observers graded each eye using the ATN system. Mean A, T, and N scores were calculated and correlated with age, BCVA (in logarithm of the minimum angle of resolution), and axial length. Patients were considered to present severe PM if either A or T components were ≥3 and/or N was ≥2.

Results:

Hundred eyes (53 left) from 91 patients (78 women) were classified. Mean age, BCVA, and axial length values were, respectively, 65.1 ± 11.7 years (range, 36–97 years), −0.63 ± 0.62 (−3.00 to 0.00), and 29.26 ± 2.7 mm (26.01–37.66 mm). Mean ATN grades for each component were as follows: A = 2.51 ± 0.78 (0.6–4.0), T = 0.88 ± 1.14 (0.0–5.0), and N = 1.31 ± 1.40 (0.0–3.0). Weighted interobserver agreement was 98.1%, 98.7%, and 94.6%, for A, T and N, respectively. In eyes with severe PM, BCVA was significantly lower and axial length was significantly longer.

Conclusion:

The excellent interobserver rate in this study demonstrates that the updated ATN grading system is an accurate and reliable tool to classify patients with PM. These findings show that BCVA is more compromised in eyes with severe PM, particularly those graded ≥A3 and/or T3.
FULL-THICKNESS MACULAR HOLE IN AGE-RELATED MACULAR DEGENERATION PATIENTS WITH TWO DISTINCT ENTITIES
Authors: Rabina Gilad , Pillar Shani , Nemet Achia , Mimouni Michael , Levinger Nadav , Chowers Itay , Ehrlich Rita , Gal-Or Orly , Barequet Dana , Rosenblatt Amir , Moisseiev Elad , Greifner Hillel , Magal Itay , Segal Ori
Published: February 2021

Purpose:

To describe optical coherence tomography characteristics of full-thickness macular holes (FTMHs) in age-related macular degeneration patients.

Methods:

A multicenter, retrospective, observational case series of patients diagnosed with age-related macular degeneration and FTMHs seen between January 1, 2009, and January 3, 2020. Clinical charts and spectral-domain optical coherence tomography images were reviewed. Optical coherence tomography findings included FTMH-inverted trapezoid or hourglass appearance, central macular thickness (CMT), complete retinal pigment epithelium and complete retinal outer retinal atrophy, and presence of pigment epithelium detachment and epiretinal membrane. The mean outcome was the morphologic and functional characterization of different subtypes of FTMHs.

Results:

A total of 86 eyes of 85 consecutive patients, with mean age of 80.31 ± 8.06 and mean best-corrected visual acuity of 1.17 ± 0.58 logarithm of the minimal angle of resolution. Two different subtypes of FTMHs were identified: tractional and degenerative. Fifty (58%) degenerative FTMHs characterized with inverted trapezoid appearance and 36 (42%) tractional FTMHs characterized with hourglass appearance. Degenerative FTMHs presented with 66% of CMT < 240 µm, 14% of CMT > 320, and 70% of complete retinal outer retinal atrophy, in comparison with 41% of CMT < 240 µm, 42.9% of CMT > 320%, and 20% of complete retinal outer retinal atrophy in the tractional FTMH group (P = 0.002, 0.003, <0.001, respectively). The presence of epiretinal membrane and pigment epithelium detachment where significantly higher in tractional FTMHs (P = 0.02, 0.03, respectively).

Conclusion:

Degenerative and tractional FTMHs may be two distinct clinical entities. Discerning degenerative from tractional FTMHs is possible by using optical coherence tomography features including shape of the FTMHs, CMT, internal–external ratio of FTMHs, and presence of complete retinal outer retinal atrophy, pigment epithelium detachment, and epiretinal membrane.
Insect Fungus Metarhizium robertsii Is a Rare Causative Agent of Keratitis
Authors: Palazzolo Laura , Kowalski Regis P. , Nayyar Shannon V. , Jhanji Vishal , Prakash Gaurav
Published: February 2021

Purpose:

This study aimed to describe a case of keratitis secondary to Metarhizium robertsii, a soil-dwelling fungus with typical insect pathogenicity.

Methods:

A Case report.

Results:

A 58-year-old man with a ocular history of soft contact lens overwear, poor contact lens hygiene, and ocular exposure to ground well water supplying his house was referred to our university practice for a central corneal ulcer with 40% thinning. Same-day rapid microscopic detection with Giemsa stain identified the presence of many hyphae elements, and he was ultimately diagnosed with M. robertsii keratitis. The patient's course involved severe and progressive corneal thinning that stabilized over a 3-month course of antifungal therapy.

Conclusions:

Metarhizium robertsii seems more aggressive than other forms of fungal keratitis; therefore, this infection may be watched more closely with the risk for quick progressive corneal thinning, even while on antifungal management.
COL14A1 promotes self-renewal of human liver cancer stem cells through activation of ERK signaling
Authors: Kong Ruijiao , Liu Haidong , Shi Yi , Man Qiuhong , Liu Shanrong
Published: February 2021

Objective:

Liver cancer stem cells (CSCs) are the culprits of hepatocellular carcinoma metastasis and recurrence. Only by eliminating tumor stem cells can malignant tumors be fundamentally cured. This study aimed to identify the role and underlying mechanism of aberrant Collagen Type XIV Alpha 1 Chain (COL14A1) overexpression in liver CSCs, and improve understanding of the molecular basis of hepatocellular carcinoma metastasis and recurrence.

Methods:

First, quantitative real-time polymerase chain reaction was used to confirm aberrant high-expression of COL14A1 in liver CSCs. Next, interference experiments were performed to determine the key role of COL14A1. To explore the mechanism of COL14A1 overexpression in liver CSCs, putative microRNA (miRNAs) targeting COL14A1 were analyzed using the miRTarBase database. Next, quantitative real-time polymerase chain reaction, western blotting, and luciferase reporter assays were performed to verify the interaction between miR-7108-3p and COL14A1. Lastly, key target proteins of the COL14A1-extracellular-regulated signal kinase (ERK) signaling pathway were identified through western blotting analysis. This study was approved by the Ethics Committee of Shanghai Fourth People’s Hospital, Tongji University School of Medicine, China (approval No. 2019tjdx17) on February 21, 2019.

Results:

COL14A1 is abnormally highly expressed in liver CSCs, which is necessary for liver CSCs to maintain their self-renewal capability. Mechanistically, COL14A1 is post-transcriptionally regulated by miR-7108-3p in a negative manner. Low expression of miR-7108-3p increased translation of COL14A1, which subsequently activated ERK signaling, ultimately maintaining the self-renewal and stem cell-like properties of liver CSCs.

Conclusion:

COL14A1, which is negatively regulated by miR-7108-3p, was found to play a crucial role in maintaining the self-renewal and stem cell-like properties of liver CSCs through activation of ERK signaling.
The Mediation and Suppression Effect of Demoralization in Breast Cancer Patients After Primary Therapy: A Structural Equation Model
Authors: PENG Hsiu-Ling , HSUEH Hui-Wen , CHANG Yu-Hsing , LI Ren-Hau
Published: February 2021

Background

Because of the increasing 5-year survival rate of breast cancer, adjustment to breast cancer survivorship is pertinent to the patient's life after diagnosis. Despite the psychological changes occurring during the transitional period (first 5 years after diagnosis) and after primary therapy having a known, critical effect on survivorship status, the data related to this topic are very limited.

Purpose

This study was designed to examine the relationships among demoralization, stress, sleep disturbance, and psychological well-being in women with breast cancer after primary therapy.

Methods

Two hundred eight women with breast cancer (mean age = 51.96 ± 8.27) participated in a cross-sectional study in central Taiwan. Recruitment was conducted using convenience snowball sampling at a local teaching hospital. All of the participants had completed primary therapy and were in the 5-year postdiagnosis period. The average duration of cancer was 28 months. The participants completed the Stress of Breast Cancer after Primary Therapy Scale, Demoralization Scale, Pittsburgh Sleep Quality Inventory, and Ryff's Psychological Well-Being Scale–Short Form. Data were analyzed using a structural equation model to find plausible path relationships among stress, demoralization, sleep disturbances, and psychological well-being.

Results

Demoralization was shown to completely mediate the effect of stress on sleep disturbances. In addition, the predictive effect of sleep disturbances on psychological well-being was overwhelmingly explained by demoralization when competing with sleep disturbances. Furthermore, a positive path was found between stress and psychological well-being because of the suppression effect of demoralization.

Conclusions/Implications for Practice

Demoralization was found to be a mediator that suppressed the relationships among stress, sleep disturbances, and psychological well-being in the adaptation process of patients with breast cancer after primary therapy. This article adds to the limited research on women with breast cancer after primary therapy who are in their initial 5 years of diagnosis. In addition, this study used structural equation model to find the plausible path relationships among the psychological factors involved in the well-being of women with breast cancer. Supporting patients with cancer and effectively reducing their perceived demoralization will be key to transforming stress into personal growth and a facilitator of long-term recovery.
Effect of a Breathing Exercise on Respiratory Function and 6-Minute Walking Distance in Patients Under Hemodialysis: A Randomized Controlled Trial: [RETRACTED]
Authors: ARAZI Tajmohammad , ALIASGHARPOUR Mansooreh , MOHAMMADI Sepideh , MOHAMMADI Nooredin , KAZEMNEJAD Anoushirvan
Published: February 2021

Background

Pulmonary disorders and poor functional capacity are common complications in patients under hemodialysis. Although breathing exercise is frequently prescribed to improve respiratory function, its efficacy in this patient community is not well established.

Purpose

Our study was designed to determine the effectiveness of a breathing exercise on respiratory function and 6-minute walk (6MW) distance in patients under hemodialysis.

Methods

A randomized controlled trial approach was used. The sample consisted of 52 patients under hemodialysis from a university teaching hospital in Iran. The experimental group (n = 26) received the breathing exercise program and was encouraged to perform incentive spirometry for 2 months. The control group (n = 26) received only routine hospital care. The respiratory function test and 6MW test were performed at baseline and at 2 months after the intervention (posttest).

Results

The two groups were homogeneous in terms of respiratory function parameters, 6MW distance, and demographic characteristics at baseline. Forced expiratory volume in 1 second and forced vital capacity were significantly better in the experimental group compared with the control group at 2 months after intervention. No significant difference was found in 6MW distance between the groups at the 2-month posttest.

Conclusions/Implications for Practice

The 2-month breathing exercise effectively improved pulmonary function parameters (forced vital capacity, forced expiratory volume in 1 second) in patients under hemodialysis but did not affect 6MW distance. Hemodialysis nurses should strengthen their clinical health education and apply breathing exercise programs to reduce the pulmonary complications experienced by patients under hemodialysis.
Dual use of Department of Veterans Affairs and community healthcare: Homeless veterans' experiences, perspectives, and perceptions
Authors: Etchin Anna G. , LaCoursiere-Zucchero Terri , McDannold Sarah E. , McInnes D. Keith
Published: February 2021

Background:

Veteran homelessness is a pervasive problem and a high-priority, mission-oriented area of investigation in the United States (US). Most veterans enrolled in healthcare with the Department of Veterans Affairs (VA) carry additional health coverage, which may increase their access to care. For veterans, dual use of VA and non-VA healthcare has potentially positive and negative consequences.

Purpose:

To explore homeless veterans' experiences seeking and obtaining healthcare within and outside the VA.

Methodology:

US homeless veterans were recruited from a large, urban Northeast Healthcare for the Homeless program from two sites. This was a descriptive phenomenological study. Three semistructured focus group interviews were conducted (total n = 21 distinct participants). We used inductive content analysis procedures to identify main themes in the data.

Results:

We found four main themes: dual use decision making, access to care, preferences and perceptions of care, and suggestions for improving VA care. Although veterans in our sample had mixed positive and negative experiences with both systems, positive responses were more common regarding community care than VA. Veterans provided more verbose responses when describing negative VA experiences and more succinct responses for positive experiences.

Conclusions:

We found mixed positive and negative experiences for both healthcare systems, although reports were more positive for non-VA care than VA.

Implications:

Veterans' healthcare concerns and needs appeared difficult to meet. Future research is warranted to improve veteran-centered care access and care experiences.
Impact of a nutrition education program on health behaviors in a university workplace wellness program
Authors: Downes Loureen S. , Buchholz Susan W. , Fogg Louis F.
Published: February 2021

Background:

Obesity is a complex health issue associated with the leading causes of preventable chronic diseases, such as heart disease and type 2 diabetes. As part of an interprofessional team, nurse practitioners can play an integral role in leading worksite interventions to enhance health behavior change. Although worksite nutrition interventions have existed for many years, effective weight management programs are needed in the workplace.

Purpose:

The purpose of this study was to determine the effect of a novel nutrition education program implemented in the workplace on health behaviors (dietary habits and physical activity), motivators and barriers, emotional eating, confidence, and biometrics (body mass index and lipid levels).

Methods:

A total of 96 university employees participated in a one-group pre- and postintervention from 2017 to 2019. The intervention included eight weekly face-face education sessions. We assessed dietary habits, physical activity, motivators and barriers of a healthy lifestyle, emotional eating, confidence levels, body mass index, and lipid levels. Descriptive statistics, chi-square test, one-way analysis of variance, and Wilcoxon rank test were performed.

Results:

The consumption of fruits, vegetables, beans, grains, and physical activity increased significantly. Barriers, body mass index, and triglycerides significantly decreased. There was no significant difference in emotional eating and motivators after the intervention.

Implications for practice:

Nurse practitioners are positioned to lead an interprofessional team to provide nutrition education to help mitigate risk factors for obesity in various settings, including the workplace.
The development and implementation of an advanced practice registered nurse–led prenatal education program for housing insecure women
Authors: McCormack Leslie , Ward Nicole , Bryant-Moore Keneshia , Kalkwarf Shannon , English Beverly , Riley Elizabeth
Published: February 2021

Housing insecurity has been shown to have an impact on the health care system due to negative maternal and neonatal outcomes. Housing insecurity is associated with the social determinants of health under the umbrella of economic stability and neighborhood/physical environments. Research shows that educational programs and support resources can help alleviate this strain for women who are pregnant. This article discusses the development and implementation of an advanced practice registered nurse (APRN)-led, prenatal education group for women facing housing insecurity who are pregnant and high risk. The curriculum was revised and based on a March of Dimes Becoming a Mom with alignment to Maslow's Hierarchy of Needs. The 10-week prenatal education program was created and implemented by a group of APRNs and registered nurses to aid pregnant women facing housing insecurity with coping strategies and education regarding their pregnancy.
Empowering nurse practitioners to make health policy CHANGE: Steps to successful passage of legislation in Utah
Authors: Eden Lacey M. , Merrill Heather , Luthy Karlen E.
Published: February 2021

Nurse practitioners have the skills needed to make meaningful policy change to improve health care. In 2017, the authors championed a bill, House Bill 308 Substitution 2 (HB 308 Sub 2), which passed in the Utah Legislature. This health policy article details the process of successful passage of HB 308 Sub 2 and guides advanced practice registered nurses (APRNs) in enacting legislation. The steps detailed to enact legislation are based on Longest's policy framework (2006). The acronym CHANGE was developed and stands for collecting data, hinge, associations, negotiate, gather, and expect to be the expert. Intricacies of lawmaking are also explained including timing of legislation, the three readings, and lobbying. The CHANGE acronym outlines the following: Collecting data to legitimize the problem and proposed solution. The Hinge refers to the specifics of the proposed solution. Associations involve garnering support from key stakeholders early and often in the legislative process. Negotiate refers to finding a bill sponsor that is trustworthy, negotiates well, and has political capital. Gather public support is a critical step to increase legislatures' constituent communication requesting support for the bill. Expect to be the expert refers to understanding arguments for and against the bill and crafting power statements. Passing of HB 308 Sub 2, through the work of APRNs, provides a step-by-step guide to successful passing of legislation. This guide will empower APRNs across the nation with the knowledge to enact and pass policies to improve health care in our nation.
From bench to bedside: updates in basic science, translational and clinical research on muscle fatigue in cancer cachexia
Authors: Jackson Katherine M. , Cole Calvin L. , Dunne Richard F.
Published: February 2021

Purpose of review

Cancer cachexia is a syndrome of loss of weight and muscle mass that leads to reduced strength, poor physical performance and functional impairment. Muscular fatigue is a distressing syndrome that patients with cachexia suffer from and can impair quality of life. Here, we review recent updates in muscular fatigue in cancer cachexia research with a focus on mechanisms, biomarkers and potential therapies.

Recent findings

Both in mice and humans, research has shown that muscle fatigue can be independent of muscular atrophy and can happen early in cancer development or in precachexia. Inflammatory pathways, mitochondrial dysfunction and gut microbiota have recently been studied to play an important role in muscle fatigue in preclinical models. Exercise can target these pathways and has been studied as a therapeutic intervention to improve muscle fatigue.

Heightened inflammation within muscle, altered muscle function and muscle fatigue can begin prior to clinical evidence of cachexia, making early recognition and intervention challenging. The emergence of cachexia mouse models and translational and clinical research studying muscle fatigue will hopefully lead to new therapies targeting the underlying mechanisms of cancer cachexia. Exercise will need to be tested in larger randomized studies before entering into daily practice.