bluuebunny/crossref_metadata_2025 huggingface dataset:
Recombinant norovirus capsid protein VP1 (GII.4) expressed in H5 insect cells exhibits post-translational modifications with potential impact on lectin activity and vaccine design
Authors: Hanisch Franz-Georg
Published: March 2022

Although surface proteins of most enveloped viruses are glycosylated, among non-enveloped viruses only few express glycoproteins in their capsid as infective virions. Noroviruses belong to the latter group and are known to express one major capsid protein (VP1) that lacks genuine glycosylation. In the context of vaccine development based on virus-like particles (VLPs) and in searches for food additives offering potential prophylactic or therapeutic applications an increasing number of reports refers to the use of VLPs that were produced as secretory products in insect cells. We asked the question whether recombinant VLPs (GII.4 Sydney, 2012) produced via the baculovirus vector in H5 insect cells may be glycosylated in the protruding domains that are involved in receptor binding and immune reactivity. Mass spectrometric analysis of tryptic VP1 peptides prior to and after beta-elimination Michael addition in 70% ethylamine revealed Thr238, and Ser519 in the P1 domain, and Thr350, Thr369, Thr371, and Thr381 in the P2 domain as modified. Thr65, Ser67, and Thr350 were revealed by liquid chromatography-mass spectrometry to carry HexNAc or Hex-HexNAc modifications, respectively. Monosaccharide analysis by gas chromatography–mass spectrometry confirmed the presence of GlcNAc on VLP protein, whereas immunoassays with lectins and antibodies demonstrated O-linked GlcNAc on VP1 protein. Post-translational modifications of virus capsid proteins may contribute to a modulation of immunodominant surface epitopes and need to be considered in anti-norovirus vaccine design. Some modifications are located near amino acid side chains involved in the binding of blood group active sugar receptors.
Poland and Hungary’s EU membership: On not confronting authoritarian governments
Authors: De Búrca Gráinne
Published: March 2022

This Reflection considers why Poland’s and Hungary’s membership of the European Union has remained in many ways unaffected by widespread, serious, and documented actions on the part of those two governments which have gravely weakened the rule of law, democracy, and human rights. The Reflection does not argue for expulsion of these states, but investigates why it is that the European Union’s political institutions and actors (rather than its supranational bodies) have not been willing to confront Poland and Hungary more robustly. The willingness of EU actors to overlook growing authoritarianism in Poland since the Russian invasion of Ukraine highlights these concerns even more starkly.
Trajectories: a framework for detecting temporal clinical event sequences from health data standardized to the Observational Medical Outcomes Partnership (OMOP) Common Data Model
Authors: Künnapuu Kadri , Ioannou Solomon , Ligi Kadri , Kolde Raivo , Laur Sven , Vilo Jaak , Rijnbeek Peter R , Reisberg Sulev
Published: March 2022

Objective

To develop a framework for identifying temporal clinical event trajectories from Observational Medical Outcomes Partnership-formatted observational healthcare data.

Materials and Methods

A 4-step framework based on significant temporal event pair detection is described and implemented as an open-source R package. It is used on a population-based Estonian dataset to first replicate a large Danish population-based study and second, to conduct a disease trajectory detection study for type 2 diabetes patients in the Estonian and Dutch databases as an example.

Results

As a proof of concept, we apply the methods in the Estonian database and provide a detailed breakdown of our findings. All Estonian population-based event pairs are shown. We compare the event pairs identified from Estonia to Danish and Dutch data and discuss the causes of the differences. The overlap in the results was only 2.4%, which highlights the need for running similar studies in different populations.

Conclusions

For the first time, there is a complete software package for detecting disease trajectories in health data.
Synthetic Mammography: Review of Benefits and Drawbacks in Clinical Use
Authors: Chikarmane Sona
Published: March 2022

Digital breast tomosynthesis (DBT) has been widely adopted as a breast cancer screening tool, demonstrating decreased recall rates and other improved screening performance metrics when compared to digital mammography (DM) alone. Drawbacks of DBT when added to 2D DM include the increased radiation dose and longer examination time. Synthetic mammography (SM), a 2D reconstruction from the tomosynthesis slices, has been introduced to eliminate the need for a separate acquisition of 2D DM. Data show that the replacement of 2D DM by SM, when used with DBT, maintains the benefits of DBT, such as decreased recall rates, improved cancer detection rates, and similar positive predictive values. Key differences between SM and 2D DM include how the image is acquired, assessment of breast density, and visualization of mammographic findings, such as calcifications. Although SM is approved by the Food and Drug Administration and has been shown to be non-inferior when used with DBT, concerns surrounding SM include image quality and artifacts. The purpose of this review article is to review the benefits, drawbacks, and screening performance metrics of SM versus DBT.
Examination of Nocturnal Oviposition by Chrysomya putoria (Diptera: Calliphoridae) in Brazil
Authors: Carneiro L T , Azevedo W T A , Aguiar V M , Couri M S
Published: March 2022

This is the first study in Brazil that monitored the nocturnal oviposition behavior of Chrysomya putoria, a species of forensic importance, in order to verify if individuals of this species oviposit at night. Groups of 10 flies (5 male and 5 female) distributed in ten cages were kept in a fume hood and submitted to total darkness or exposed to artificial light for eleven consecutive hours through four experimental conditions in the laboratory. Two verifications were made to see if the females oviposited in the offered substrate of about 20 g of chicken gizzard per cage. Verification 1 occurred at 09:00 pm in the evening experiments and at 09:00 am in the daytime experiments. Verification 2 occurred at 05:00 am in the night experiments and at 05:00 pm in the daytime experiments. Each experiment lasted 5 d. C. putoria laid eggs at night (with or without light) and the quantity of eggs was significantly similar to those produced during the day under natural light or in total darkness. Only the amount of eggs produced during the day in the absence of light was considerably greater than in the typical daytime period. The females oviposited in greater quantity in the nights when the average temperature was between 23 and 24.8°C and relative humidity above 81%. Ovipositions only occurred at temperatures above 21°C and humidity above 56% during the day. Finally, it is necessary that more evaluations on the effect of variables on blowfly behavior are performed to better understand nocturnal oviposition.
The Effectiveness of a Standardized Ice-Sheet Cooling Method Following Exertional Hyperthermia
Authors: Caldwell Aaron R , Saillant Michelle M , Pitsas Dina , Johnson Audrey , Bradbury Karleigh E , Charkoudian Nisha
Published: March 2022

Introduction

Exertional heat illnesses remain a major threat to military service members in the United States and around the world. Exertional heat stroke (EHS) is the most severe heat illness, characterized by core hyperthermia and central nervous system dysfunction. Per current Army regulations, iced-sheet cooling (ISC) is the recommended immediate treatment for heat casualties in the field, but concerns have been raised regarding the efficacy of this approach. Thus, the purpose of this study was to quantify the cooling rate of ISC following exertional hyperthermia.

Materials and Methods

We utilized a randomized crossover design with 2 experimental trials. In both trials, exertional hyperthermia was induced by walking (3.5 mph at 5% grade) on a treadmill in an environmental chamber (40 °C, 30% RH) for up to 3 hours or until core body temperature reached 39.2 °C. After the walking portion, individuals either received ISC (experimental trial) or cooling and rested supine in the same environmental conditions for 30 minutes with no ISC (control trial). For ISC, bed sheets soaked in ice water were applied (per Army guidance) at the neck, chest, and groin with another sheet covering the body. Sheets were rotated and resoaked every 3 minutes until core temperature decreased to <38.0 °C.

Results

By design, participants finished exercise with increased core temperature (38.8 ± 0.39 °C vs. 38.90 ± 0.34 °C, ISC and control trials, P = 1.00). The ISC trial provided significantly (P = .023) greater cooling rates, 0.068 °C/min 95% confidence interval [CI; 0.053, 0.086], compared to the control trial, 0.047 °C/min 95% CI [0.038, 0.056]. Additionally, the time to decrease to less than 38.0 °C was significantly (P = .018) faster in the ISC trial (median = 9.3 minutes) compared to the control trial (median = 26.6 minutes).

Conclusion

ISC increases the cooling rate of those recovering from exertional hyperthermia. With the observed cooling rate, we can extrapolate that ISC would reduce core temperature by ∼2 °C within 30 minutes during a case of EHS. We conclude that ISC provides a safe and effective alternative for the field where cold water immersion resources may not be readily available.
The methanol emission in the J1– J0 A−+ line series as a tracer of specific physical conditions in high-mass star-forming regions
Authors: Salii Svetlana V , Zinchenko Igor I , Liu Sheng-Yuan , Sobolev Andrej M , Aberfelds Artis , Su Yu-Nung
Published: March 2022

We present results of the investigations of the properties of the methanol J1 –J0 A−+ line series motivated by the recent serendipitous detection of the maser emission in the 141 – 140 A−+ line at 349 GHz in S255IR-SMA1 soon after the accretion burst. The study includes further observations of several lines of this series in S255IR with the SMA, a mini-survey of methanol lines in the 0.8-mm range towards a sample of bright 6.7-GHz methanol maser sources with the IRAM 30-m telescope, and theoretical modelling. We found that the maser component of the 141 – 140 A−+ line in S255IR decayed by more than order of magnitude in comparison with that in 2016. No clear sign of maser emission is observed in other lines of this series in the SMA observations except the 71 – 70 A−+ line where an additional bright component is detected at the velocity of the maser emission observed earlier in the 141 – 140 A−+ line. Our LVG model constrains the ranges of the physical parameters that match the observed emission intensities. No obvious maser emission in the J1 – J0 A−+ lines was detected in the mini-survey of the 6.7-GHz methanol maser sources, though one component in NGC 7538 may represent a weak maser. In general, the maser effect in the J1 – J0 A−+ lines may serve as a tracer of rather hot environments and in particular luminosity flaring events during high-mass star formation.
Global Population Genomics of Two Subspecies ofCryptosporidium hominisduring 500 Years of Evolution
Authors: Tichkule Swapnil , Cacciò Simone M. , Robinson Guy , Chalmers Rachel M. , Mueller Ivo , Emery-Corbin Samantha J. , Eibach Daniel , Tyler Kevin M. , van Oosterhout Cock , Jex Aaron R.
Published: March 2022

Cryptosporidiosis is a major global health problem and a primary cause of diarrhea, particularly in young children in low- and middle-income countries (LMICs). The zoonotic Cryptosporidium parvum and anthroponotic Cryptosporidium hominis cause most human infections. Here, we present a comprehensive whole-genome study of C. hominis, comprising 114 isolates from 16 countries within five continents. We detect two lineages with distinct biology and demography, which diverged circa 500 years ago. We consider these lineages two subspecies and propose the names C. hominis hominis and C. hominis aquapotentis (gp60 subtype IbA10G2). In our study, C. h. hominis is almost exclusively represented by isolates from LMICs in Africa and Asia and appears to have undergone recent population contraction. In contrast, C. h. aquapotentis was found in high-income countries, mainly in Europe, North America, and Oceania, and appears to be expanding. Notably, C. h. aquapotentis is associated with high rates of direct human-to-human transmission, which may explain its success in countries with well-developed environmental sanitation infrastructure. Intriguingly, we detected genomic regions of introgression following secondary contact between the subspecies. This resulted in high diversity and divergence in genomic islands of putative virulence genes, including muc5 (CHUDEA2_430) and a hypothetical protein (CHUDEA6_5270). This diversity is maintained by balancing selection, suggesting a co-evolutionary arms race with the host. Finally, we find that recent gene flow from C. h. aquapotentis to C. h. hominis, likely associated with increased human migration, maybe driving the evolution of more virulent C. hominis variants.
Genetic Diversity, Heteroplasmy, and Recombination in Mitochondrial Genomes ofDaphnia pulex,Daphnia pulicaria, andDaphnia obtusa
Authors: Ye Zhiqiang , Zhao Chaoxian , Raborn R. Taylor , Lin Man , Wei Wen , Hao Yue , Lynch Michael
Published: March 2022

Genetic variants of mitochondrial DNA at the individual (heteroplasmy) and population (polymorphism) levels provide insight into their roles in multiple cellular and evolutionary processes. However, owing to the paucity of genome-wide data at the within-individual and population levels, the broad patterns of these two forms of variation remain poorly understood. Here, we analyze 1,804 complete mitochondrial genome sequences from Daphnia pulex, Daphnia pulicaria, and Daphnia obtusa. Extensive heteroplasmy is observed in D. obtusa, where the high level of intraclonal divergence must have resulted from a biparental-inheritance event, and recombination in the mitochondrial genome is apparent, although perhaps not widespread. Global samples of D. pulex reveal remarkably low mitochondrial effective population sizes, <3% of those for the nuclear genome. In addition, levels of population diversity in mitochondrial and nuclear genomes are uncorrelated across populations, suggesting an idiosyncratic evolutionary history of mitochondria in D. pulex. These population-genetic features appear to be a consequence of background selection associated with highly deleterious mutations arising in the strongly linked mitochondrial genome, which is consistent with polymorphism and divergence data suggesting a predominance of strong purifying selection. Nonetheless, the fixation of mildly deleterious mutations in the mitochondrial genome also appears to be driving positive selection on genes encoded in the nuclear genome whose products are deployed in the mitochondrion.
Folate dose and form during pregnancy may program maternal and fetal health and disease risk
Authors: Pannia Emanuela , Hammoud Rola , Simonian Rebecca , Kubant Ruslan , Anderson G Harvey
Published: March 2022

The role of folate, in its synthetic and bioactive form, as an in utero modifier of metabolic outcomes in mothers and offspring is examined in this review. During pregnancy, a continuum of adaptive changes occurs to support maternal and fetal requirements. However, an unfavorable in utero environment may lead to permanent changes in cellular and physiological functions, adversely affecting the development of the child and postpartum health of the mother. In North American countries, synthetic folic acid (FA) is overconsumed by pregnant women, and uncertainty exists about its potential unintended health effects. Because the metabolism of FA is different than that of other folate forms, it may modulate disease risk differently. The bioactive form of folate, 5-methyltetrahydrofolic acid, has emerged as a popular alternative to FA, but clinical studies comparing their effects during pregnancy are limited. Current evidence points to the need for caution when maternal intake of either folate form exceed recommended amounts. Research directed toward defining an optimal folate dose and form for healthy pregnancy and long-term metabolic outcomes in mothers and children is urgently needed.
Eosinophilic Syndromes Associated With Daptomycin Use: Re-exposure Hypersensitivity Pneumonitis and Prior Peripheral Eosinophilia
Authors: West Katelyn A , Sheeti Ahmed , Tamura MacKay Kimberly , Forrest Graeme N
Published: March 2022

Background

Daptomycin pulmonary eosinophilia (DPE) has been well described in case reports and reporting from the Food and Drug Administration. We report 3 eosinophilic syndromes associated with daptomycin use.

Methods

This is a retrospective review of all patients who received daptomycin (inpatient or outpatient) from 2010 to 2020 at the Veterans Affairs Portland Healthcare System. Patients who developed DPE while receiving daptomycin were evaluated to determine risk factors. Data collected included daptomycin dose and duration, body mass index, creatinine clearance, and peripheral eosinophilia.

Results

Of 330 patients who received daptomycin, 81.5% developed a peripheral eosinophilia, with 109 (33%) developing peripheral eosinophilia ≥5%. Fifty-one (16%) met criteria for DPE. Primary DPE occurred in 38 of the 51 patients with a median 26 days of treatment, and 49% had peripheral eosinophilia ≥5%. Re-exposure DPE occurred in the other 13 patients and occurred a median of 3 days after initiation of daptomycin. The presence of an elevated peripheral eosinophilia of ≥5% during daptomycin usage was significantly associated with primary (odds ratio [OR], 2.23; 95% CI, 1.2–4.09; P = .008) and re-exposure DPE (OR, 12; 95% CI, 1.6–103; P = .003). All patients recovered after withdrawal of daptomycin without complications.

Conclusions

There are 3 daptomycin eosinophilic syndromes: peripheral eosinophilia, primary DPE occurring about 4 weeks into therapy, and re-exposure DPE. Elevated peripheral eosinophilia ≥5% was a risk factor for both primary and re-exposure DPE, but still identified about half the cases. Peripheral eosinophilia should be carefully monitored during daptomycin treatment, and clinicians should be aware that prior eosinophilia may predict an acute pulmonary reaction upon daptomycin re-exposure.
Treatment and Outcome of Culture-Confirmed Mycobacterium marinum Disease
Authors: Hendrikx Louise , van Hees Colette L M , de Steenwinkel Jurriaan E M , Bax Hannelore I , Sprong Tom , Mulder Bert , Jansz Arjan , van Griethuysen Arjanne , Bosboom Ron , Stemerding Annette , Koetsier Marjolein , van Coevorden Marco , Mourik Bas C , Quint Koen D , Ott Alewijn , van Soolingen Dick , Kuipers Saskia , van Crevel Reinout , van Ingen Jakko
Published: March 2022

Background

Mycobacterium marinum is a nontuberculous mycobacterium that causes skin and soft tissue infections. Treatment consists of multiple antibiotics, sometimes combined with surgical debridement. There is little evidence for the choice of antibiotics, the duration of treatment, and the role of susceptibility testing.

Methods

We performed a retrospective cohort study of culture-confirmed M. marinum infections in the Netherlands in the 2011–2018 period. Clinical characteristics, in vitro susceptibility, extent of disease, treatment regimens, and outcomes were analyzed. Incidence was assessed from laboratory databases.

Results

Forty cases of M. marinum infection could be studied. Antibiotic treatment cured 36/40 patients (90%) after a mean treatment duration of 25 weeks. Failure/relapse occurred in 3 patients, and 1 patient was lost to follow-up. Antibiotic treatment consisted of monotherapy in 35% and 2-drug therapy in 63%. Final treatment contained mostly ethambutol–macrolide combinations (35%). Eleven patients (28%) received additional surgery. We recorded high rates of in vitro resistance to tetracyclines (36% of isolates). Tetracycline resistance seemed correlated with poor response to tetracycline monotherapy. The annual incidence rate was 0.15/100 000/year during the study period.

Conclusions

Prolonged and susceptibility-guided treatment results in a 90% cure rate in M. marinum disease. Two-drug regimens of ethambutol and a macrolide are effective for moderately severe infections. Tetracycline monotherapy in limited disease should be used vigilantly, preferably with proven in vitro susceptibility.
Rates of Severe Influenza-Associated Outcomes Among Older Adults Living With Diabetes—Influenza Hospitalization Surveillance Network (FluSurv-NET), 2012–2017
Authors: Owusu Daniel , Rolfes Melissa A , Arriola Carmen S , Daily Kirley Pam , Alden Nisha B , Meek James , Anderson Evan J , Monroe Maya L , Kim Sue , Lynfield Ruth , Angeles Kathy , Spina Nancy , Felsen Christina B , Billing Laurie , Thomas Ann , Keipp Talbot H , Schaffner William , Chatelain Ryan , Reed Carrie , Garg Shikha
Published: March 2022

Background

Diabetes mellitus (DM) is common among older adults hospitalized with influenza, yet data are limited on the impact of DM on risk of severe influenza-associated outcomes.

Methods

We included adults aged ≥65 years hospitalized with influenza during 2012–2013 through 2016–2017 from the Influenza Hospitalization Surveillance Network (FluSurv-NET), a population-based surveillance system for laboratory-confirmed influenza-associated hospitalizations conducted in defined counties within 13 states. We calculated population denominators using the Centers for Medicare and Medicaid Services county-specific DM prevalence estimates and National Center for Health Statistics population data. We present pooled rates and rate ratios (RRs) of intensive care unit (ICU) admission, pneumonia diagnosis, mechanical ventilation, and in-hospital death for persons with and without DM. We estimated RRs and 95% confidence intervals (CIs) using meta-analysis with site as a random effect in order to control for site differences in the estimates.

Results

Of 31 934 hospitalized adults included in the analysis, 34% had DM. Compared to those without DM, adults with DM had higher rates of influenza-associated hospitalization (RR, 1.57 [95% CI, 1.43–1.72]), ICU admission (RR, 1.84 [95% CI, 1.67–2.04]), pneumonia (RR, 1.57 [95% CI, 1.42–1.73]), mechanical ventilation (RR, 1.95 [95% CI, 1.74–2.20]), and in-hospital death (RR, 1.48 [95% CI, 1.23–1.80]).

Conclusions

Older adults with DM have higher rates of severe influenza-associated outcomes compared to those without DM. These findings reinforce the importance of preventing influenza virus infections through annual vaccination, and early treatment of influenza illness with antivirals in older adults with DM.
Three-dimensional geometry and dust/gas ratios in massive star-forming regions over the entire LMC as revealed by the IRSF/SIRIUS survey
Authors: Furuta Takuya , Kaneda Hidehiro , Kokusho Takuma , Nakajima Yasushi , Fukui Yasuo , Tsuge Kisetsu
Published: March 2022

We derive the entire dust extinction (AV) map for the Large Magellanic Cloud (LMC) estimated from the color excess at near-infrared wavelengths. Using the percentile method we recently adopted to evaluate AV distribution along the line of sight, we derive three-dimensional (3D) AV maps of the three massive star-forming regions of N44, N79, and N11 based on the IRSF/SIRIUS point source catalog. The 3D AV maps are compared with the hydrogen column densities N(H) of three different velocity components where one is of the LMC disk velocity and the other two are of velocities lower than the disk velocity. As a result, we obtain a 3D dust geometry suggesting that gas collision is ongoing between the different velocity components. We also find differences in the timing of the gas collision between the massive star-forming regions, which indicates that the gas collision in N44, N79, and N11 occurred later than that in 30 Doradus. In addition, a difference of a factor of two in AV/N(H) is found between the velocity components for N44, while a significant difference is not found for N79 and N11. From the 3D geometry and AV/N(H) in each star-forming region, we suggest that the massive star formation in N44 was induced by an external trigger of tidal interaction between the LMC and the Small Magellanic Cloud, while that in N79 and N11 is likely to have been induced by internal triggers such as gas converging from the galactic spiral arm and expansion of a supershell, although the possibility of tidal interaction cannot be ruled out.
Individual Virtues and Structures of Virtue in Public Health
Authors: Nihlén Fahlquist Jessica
Published: March 2022

Public health ethics is commonly analyzed within a consequentialist or rights-based perspective, but recent approaches explore public health from a virtue ethical perspective. Rozier focuses on the virtues of individual members of the public and I discuss public health professionals. MacKay emphasizes the role of the collective level, the practice and social structure of public health. The structure can be important in two ways. First, it potentially affects the cultivation of the virtues of individuals. Second, the structure itself could have virtues. MacKay defends the latter notion and argues that structures become objective reality that is non-reducible to individuals. She implicitly describes public health as an actor, as having hopes and aspirations. MacKay’s account is an interesting contribution to the field. I agree with that the social structure is important but argue that it is primarily important in relation to the cultivation of individual virtues. Public health is not an agent and if it is described as such, it needs a supporting argument concerning moral group agency. I argue that there are no collectives without individuals. Future studies should focus on the links between the individual and social levels and discuss which virtues are the most important.
Race in the Reading: A Study of Problematic Uses of Race and Ethnicity in a Prominent Pediatrics Textbook
Authors: Li Alice , Deyrup Andrea T. , Graves Joseph L. , Ross Lainie Friedman
Published: March 2022

Purpose

Aspects of medical education and clinical practice continue to reflect the antiquated notion that race is a biologically valid distinction among individuals rather than a social construct. The authors analyzed the use of race and ethnicity in a popular pediatrics textbook to determine if these concepts were being used consistently and correctly.

Method

In May 2021, using the search function on the American Academy of Pediatrics (AAP) eBooks platform, the authors searched for 29 race- or ethnicity-related terms (e.g., African, Asian, Black, race) in the AAP Textbook of Pediatric Care, 2nd Edition, which was published in 2016. One researcher extracted direct quotes containing at least one of these search terms. Three researchers independently coded each quote as problematic or nonproblematic with respect to the use of the search terms, excluding examples in which the terms were used in irrelevant contexts (e.g., black box warning). The researchers then identified themes based on the quotes that used race and ethnicity problematically.

Results

The search produced 2,167 total results across the search terms, 806 of which were relevant to race or ethnicity and were analyzed. Problematic quotes: (1) used race or ethnicity as a surrogate for social variables, (2) conflated terminology (e.g., conflated socially defined race with genetic ancestry), (3) overgeneralized or made claims based on limited data, (4) lacked clinical relevance, (5) lacked inclusivity, (6) promoted racial stereotypes, or (7) made contradicting claims about race.

Conclusions

The use of race and ethnicity in the AAP Textbook of Pediatric Care, 2nd Edition was not always appropriate, as demonstrated by examples that reified race as a biological fact and thereby promoted structural racism. Critical evaluation of the use of race and ethnicity in all current medical textbooks and future revisions is warranted.
Will Any Road Get You There? Examining Warranted and Unwarranted Variation in Medical Education
Authors: Holmboe Eric S. , Kogan Jennifer R.
Published: March 2022

Undergraduate and graduate medical education have long embraced uniqueness and variability in curricular and assessment approaches. Some of this variability is justified (warranted or necessary variation), but a substantial portion represents unwarranted variation. A primary tenet of outcomes-based medical education is ensuring that all learners acquire essential competencies to be publicly accountable to meet societal needs. Unwarranted variation in curricular and assessment practices contributes to suboptimal and variable educational outcomes and, by extension, risks graduates delivering suboptimal health care quality. Medical education can use lessons from the decades of study on unwarranted variation in health care as part of efforts to continuously improve the quality of training programs. To accomplish this, medical educators will first need to recognize the difference between warranted and unwarranted variation in both clinical care and educational practices. Addressing unwarranted variation will require cooperation and collaboration between multiple levels of the health care and educational systems using a quality improvement mindset. These efforts at improvement should acknowledge that some aspects of variability are not scientifically informed and do not support desired outcomes or societal needs. This perspective examines the correlates of unwarranted variation of clinical care in medical education and the need to address the interdependency of unwarranted variation occurring between clinical and educational practices. The authors explore the challenges of variation across multiple levels: community, institution, program, and individual faculty members. The article concludes with recommendations to improve medical education by embracing the principles of continuous quality improvement to reduce the harmful effect of unwarranted variation.
The Effects of Obesity and Bariatric Surgery on Rates of Upper Extremity Compression Neuropathies
Authors: Khalid Syed I. , Maasarani Samantha , Thomson Kyle B. , Pires Giovanna R. , Becerra Adan , Adogwa Owoicho , Mehta Ankit I. , Noland Shelley S. , Torquati Alfonso
Published: March 2022

Objectives:

To estimate the effects of obesity on all types of upper extremity compression neuropathies (UECN) (carpal tunnel syndrome and other median nerve, radial nerve, and ulnar nerve compression neuropathies) and to assess whether bariatric surgery modifies these effects.

Background:

UECN are increasingly prevalent and decrease the quality of life of affected individuals. Studies suggest obesity as a risk factor for carpal tunnel syndrome, the most common type of UECN.

Methods:

A retrospective cohort study was conducted using the PearlDiver Mariner Database, an all-payor claims database containing claims for over 53 million patients from 2010 to 2019 in all 50 US states. Rates and odds of all types of UECN were compared between 1:1:1 exact matched cohorts of obese patients who were medically managed, obese patients who underwent bariatric surgery, and nonobese patients (111,967 patients in each cohort).

Results:

Compared with nonobese patients, patients with obesity were significantly more likely to develop any UECN (odds ratio [OR], 1.13; 95% confidence interval [CI], 1.09–1.18), carpal tunnel syndrome (OR, 1.15; 95% CI, 1.10–1.30), and 2 or more UECN (OR, 1.34; 95% CI, 1.20–1.48). Compared with obese patients who were managed medically, obese patients who underwent bariatric surgery were significantly less likely to develop any UECN (OR, 0.87; 95% CI, 0.84–0.91) and carpal tunnel syndrome (OR, 0.85; 95% CI, 0.81–0.89).

Conclusions:

Obese patients have higher odds of both single and concomitant UECN, specifically carpal tunnel syndrome, compared with nonobese patients. Bariatric surgery decreases the odds of developing UECN compared with obese patients not undergoing surgical intervention.
Development of a Clinical Data Model Addressing the Nursing Focus “Anxiety”
Authors: Sampaio Francisco , Gonçalves Patrícia , Vieira Marques Pedro , Sequeira Carlos , Lluch Canut María Teresa
Published: March 2022

Anxiety disorders are among the most prevalent mental disorders worldwide. However, anxiety is not exclusive to anxiety disorders. In fact, the nursing discipline approaches anxiety as a human response to health conditions/life processes. Health information systems should primarily contribute to improving the quality of care, patient safety, and the effectiveness of care delivery. Nevertheless, nursing information systems still fail to incorporate evidence-based clinical data models addressing the nursing focus “anxiety.” Thus, this study aimed to obtain consensus on the data to be included in a clinical data model addressing the nursing focus “anxiety,” its organization, and its interrelationships by using a brainstorming session and a modified e-Delphi technique with a panel of nurse experts from across Portugal. Eight experts participated in the brainstorming session. A total of 59 and 54 participants completed the survey in e-Delphi rounds 1 and 2, respectively. Consensus was achieved to all data presented to the participants, and these data were later included in the clinical data model. This evidence-based clinical data model, grounded on a nursing theory and with standardized nursing language, will substantially contribute to nursing documentation and, consequently, to nursing care targeted at patients with anxiety.
Therapeutic Drug Monitoring of Antibiotics in Critically Ill Children: An Observational Study in a Pediatric Intensive Care Unit
Authors: de Cacqueray Noémie , Boujaafar Sana , Bille Emmanuelle , Moulin Florence , Gana Inès , Benaboud Sihem , Hirt Déborah , Béranger Agathe , Toubiana Julie , Renolleau Sylvain , Tréluyer Jean M. , Oualha Mehdi
Published: March 2022

Background:

Septic critically ill children are at a high risk of inadequate antibiotic exposure, requiring them to undergo therapeutic drug monitoring (TDM). The aim of this study was to describe the use of TDM for antibiotics in critically ill children.

Methods:

The authors conducted a single-center observational study between June and December 2019, with all children treated with antibiotics in a pediatric intensive care unit located in a French university hospital. Standard clinical and laboratory data were recorded. Blood samples were collected for routine laboratory tests, and plasma antibiotic levels were assayed using validated analytical methods.

Results:

A total of 209 children received antibiotics. TDM was performed in 58 patients (27.8%) who had a greater mean organ dysfunction (according to the International Pediatric Sepsis Consensus Conference) (3 versus 1 in the non-TDM group; P < 0.05) and were treated with antibiotics for longer. A total of 208 samples were analyzed. The median [interquartile range] assay turnaround time was 3 (1–5) days, and 48 (46.2%) of the 104 initial antibiotic concentration values were below the pharmacokinetic/pharmacodynamic targets. A total of 34 (46%) of the 74 off-target TDM measurements available before the end of the antibiotic treatment prompted dose adjustment. This dose adjustment increased the proportion of on-target TDM measurements (70% versus 20% without adjustment). Subsequent measurements of the minimum inhibitory concentration showed that the use of the European Committee on Antimicrobial Susceptibility Testing's epidemiological cutoff values led to underestimation of pharmacokinetic/pharmacodynamic target attainment in 10 cases (20%).

Conclusions:

TDM seems to be an effective means of optimizing antibiotic exposure in critically ill children. This requires timely plasma antibiotic assays and minimum inhibitory concentration measurements. It is important to define which patients should undergo TDM and how this monitoring should be managed.
Short-Term Neurologic Manifestations of Repetitive Head Impacts Among Athletes: A Scoping Review
Authors: Stephen Steve J. , Hasman Linda , Goldenberg May , Merchant-Borna Kian , Kawata Keisuke , Mannix Rebekah , Bazarian Jeffrey J.
Published: March 2022

Objective:

To summarize the evidence linking contact sports–related repetitive head impacts (RHIs) and short-term declines in neurologic function.

Methods:

A scoping review following the guidelines in the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) and searching 3 databases (PubMed, EMBASE, and Web of Science) was performed. Peer-reviewed research articles were eligible for inclusion if they were full-length English language articles published between 1999 and 2019 examining athletes between the ages of 14 and 40 years exposed to RHIs, and reporting cognitive, vestibular, and/or oculomotor outcomes within 4 weeks of last head hit exposure.

Results:

Fifty-two articles met criteria for review: 14 reported oculomotor outcomes, 23 reported vestibular outcomes, and 36 reported cognitive function. Short-term RHI-related declines in neurologic function were reported in 42.9% of oculomotor studies, in 20.8% of vestibular studies, and in 33.3% of cognitive studies. Most of the 52 studies involved American football, soccer, or ice hockey athletes at the collegiate (n = 23) or high school (n = 14) level. Twenty-four (46%) studies involved only male athletes. Wearable sensors were used to measure RHIs in 24 studies (46%), while RHIs were not measured in 26 studies (50%). In addition, many studies failed to control for attention-deficit/hyperactivity disorder/learning disability and/or concussion history.

Conclusion:

The results of this scoping review suggest that the evidence linking RHIs to short-term declines in neurologic function is relatively sparse and lacking in methodological rigor. Although most studies failed to find a link, those that did were more likely to use objective measures of RHIs and to control for confounders. More careful trial design may be needed to definitively establish a causal link between RHIs and short-term neurologic dysfunction.
Optimization of the Parameters for the Test Bolus Technique in Computed Tomography Angiography of Head and Neck
Authors: Zeng Yuli
Published: March 2022

Objective

The aim of the study was to optimize low-dose scanning protocols for the test bolus technique in 64-detector computed tomography (CT) angiography (CTA) of the head and neck.

Methods

A total of 250 patients were randomly divided into 5 groups of 50 patients each: conventional group (group A: 120 kV, 100 mA) and low-dose groups (group B: 100 kV, 100 mA; group C: 100 kV, 50 mA; group D: 80 kV, 100 mA; and group E: 80 kV, 50 mA). Subjective scores and objective measurements (CT values of the aortic arch, image noise, and signal-to-noise ratio) were used to evaluate the image quality and compare the radiation doses of the 5 groups.

Results

The image quality of the 5 groups met the diagnostic requirements, with no significant difference in the subjective evaluation findings (P > 0.05). There were significant differences in the CT values between the conventional group and low-dose groups (P < 0.05); however, there was no significant difference between groups B and C and between groups D and E (P > 0.05). Moreover, the volume CT dose index and dose length product of groups B, C, D, and E decreased by 37.62%, 70.45%, 65.28%, and 83.39%, respectively, compared with those of group A. Although the image noise of the low-dose groups increased, an appropriate reduction in the tube voltage enhanced the contrast medium-induced x-ray attenuation and increased the CT value, which resulted in a nonsignificant difference in the signal-to-noise ratio. Therefore, the image quality of the low-dose groups was not affected compared with that of the conventional group.

Conclusions

In the test bolus technique in 64-detector CTA, the low-dose protocol of using 80 kV and 50 mA reduces the radiation dose by 83.39% compared with the conventional scan, without affecting the image quality.
Synergistic Role of Quantitative Diffusion Magnetic Resonance Imaging and Structural Magnetic Resonance Imaging in Predicting Outcomes After Traumatic Brain Injury
Authors: Avesta Arman , Yendiki Anastasia , Perlbarg Vincent , Velly Lionel , Khalilzadeh Omid , Puybasset Louis , Galanaud Damien , Gupta Rajiv
Published: March 2022

Objective

This study aimed to assess if quantitative diffusion magnetic resonance imaging analysis would improve prognostication of individual patients with severe traumatic brain injury.

Methods

We analyzed images of 30 healthy controls to extract normal fractional anisotropy ranges along 18 white-matter tracts. Then, we analyzed images of 33 patients, compared their fractional anisotropy values with normal ranges extracted from controls, and computed severity of injury to white-matter tracts. We also asked 2 neuroradiologists to rate severity of injury to different brain regions on fluid-attenuated inversion recovery and susceptibility-weighted imaging. Finally, we built 3 models: (1) fed with neuroradiologists' ratings, (2) fed with white-matter injury measures, and (3) fed with both input types.

Results

The 3 models respectively predicted survival at 1 year with accuracies of 70%, 73%, and 88%. The accuracy with both input types was significantly better (P < 0.05).

Conclusions

Quantifying severity of injury to white-matter tracts complements qualitative imaging findings and improves outcome prediction in severe traumatic brain injury.
Multiparametric Large Field of View Rheumatology Imaging for Axial Spondyloarthropathy Detects Enthesitis in Setting of Inactive Sacroiliac Joint Disease and Impacts Clinical Diagnosis
Authors: Boraiah Girish , Soldatos Theodoros , Thakur Uma J. , Chhabra Avneesh
Published: March 2022

Aim

To test the diagnostic efficacy of a multiparametric rheumatology lumbosacral magnetic resonance (MR) imaging protocol in detection and characterization of axial spondylarthritis (SpA) and compare it with serology and clinical findings.

Methods

A consecutive series of multiparametric rheumatology lumbosacral MR imaging examinations performed on 3T MR scanner. Three-dimensional inversion recovery turbo spin echo, precontrast and postcontrast fat-suppressed T1-weighted images, as well as diffusion-weighted images were used to detect active erosions and enthesitis using established criteria. Pearson χ2 was used for categorical variables. Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were measured for magnetic resonance imaging (MRI) and serology, based on the final diagnosis from rheumatologists. An alpha error below 0.05 was considered statistically significant.

Results

The final study sample included 130 consecutive patients (80 women and 50 men; mean ± SD 44 ± 13 and 45 ± 14 years, respectively). Seventy-eight subjects were diagnosed with axial SpA and 52 with non-SpA arthropathy. In the non-SpA group, 27 patients were diagnosed with osteoarthritis, 6 had unremarkable imaging, whereas 19 were considered as clinically undetermined. There was positive correlation between positive MRI results and SpA diagnosis (P < 0.00001). No correlation existed between positive serology alone and SpA diagnosis (P = 0.0634). Although MRI and serology proved equally sensitive in detecting SpA, the specificity and overall accuracy of MRI were significantly higher. Inflammatory activity was detected in 45 (57.7%) cases, in the pelvic enthesis in 29 (37.2%) cases, in the lumbosacral spine in 16 (20.5%) cases, in the hip joints in 15 (19.2%) cases, and in the pubic symphysis in 5 (6.4%). Inactive sacral disease was seen in 7 of 35 enthesitis patients (20.0%), and in 2 SpA cases, there were no sacral lesions.

Conclusions

The results suggest that in patients with suspected SpA, MRI should not be limited to the sacroiliac joints, but also include enthesitis sites and other joints of the axial skeleton. The multiparametric rheumatology protocol increases the efficacy of MRI in detecting enthesitis and joint inflammatory disease, thereby offering additional information to the clinician and assisting in the early diagnosis/detecting disease activity.
Normative Reference Values for Knee Extensor Muscle Rate of Torque Development and Torque Steadiness in Adolescents and Adults
Authors: Ong Jia Hui , Simic Milena , Eisenhuth John , Burns Joshua , Baldwin Jennifer N. , McKay Marnee J.
Published: March 2022

Objective

The aim of this study was to establish reference values for rate of torque development (RTD) and muscle torque steadiness (MTS) of knee extensors across the lifespan, and evaluate if these measures are independently associated with Osteoarthritis Research Society International (OARSI)–recommended performance-based measures (6-minute walk test, 30-second chair stand test, stair climb test) and other clinical variables.

Methods

In this cross-sectional observational study, knee extensor strength of 764 participants (12–89 years) from the 1000 Norms Project was assessed via fixed dynamometry. Age- and sex-stratified normative RTD (Nms−1 kg−1) and MTS (Nm kg−1) values were presented as means and 95% confidence intervals. Correlations and multiple regression analyses were calculated to identify factors (age, sex, height, weight, OARSI-recommended performance-based measures, Knee Injury and Osteoarthritis Outcome Score, vertical jump, long jump, grip strength, basic gait-related knee biomechanics) independently associated with RTD or MTS.

Results

Age- and sex-stratified normative RTD and MTS reference values were generated. Male subjects exhibited higher RTD but poorer MTS (less steady) than female subjects across all age groups. Better performance in OARSI-recommended performance-based measures, vertical jump, long jump, and grip strength were associated with greater RTD but poorer MTS. Thirty-second chair stand test, stair climb test, vertical jump, long jump, and grip strength were independent determinants of RTD and MTS.

Conclusions

The RTD and MTS demonstrated associations with clinical variables relevant to knee osteoarthritis. The normative reference values generated may help identify the presence and extent of impairments in RTD and MTS associated with knee osteoarthritis and assist in developing responsive outcome measures for therapeutic trials.
Potential Benefit of Rituximab in Rhupus Patients From a Single-Center
Authors: Rottenberg Pascal , Brevet Pauline , Leclercq Mathilde , Jouen Fabienne , Marie Isabelle , Lévesque Hervé , Lequerré Thierry , Vittecoq Olivier
Published: March 2022

Background

Rhupus syndrome is better characterized, but uncertainties remain, and therapeutic management must be defined. The objective was to analyze therapeutic procedures with a focus on biologic disease-modifying antirheumatic drugs (bDMARDs).

Methods

This 10-year medical records review was based on diagnosis codes (rheumatoid arthritis [RA] and systemic lupus erythematosus [SLE]) and biological data (anti-CCP testing, anti-dsDNA, and anti-RNP antibodies). Patients fulfilling 2010 ACR/EULAR and 2012 SLICC and/or 2019 ACR/EULAR classification criteria for RA and SLE, respectively, were included.

Results

Sixteen patients were identified. Rheumatoid arthritis most often preceded rhupus, with predominant articular pattern; 11 of them had erosive arthropathy. Skin involvement was the most frequent associated manifestation (n = 12). Serious events were reported, including active glomerulonephritis (n = 3), ischemic stroke (n = 1), and myocardial infarction (n = 1). Immunological profiles showed positivity for antinuclear (n = 16), anti-dsDNA (n = 9), and anti-CCP (n = 9). Ten patients required bDMARDs. All types of RA-approved bDMARDs were used. Abatacept was considered effective in 3 of the 4 patients, with 1 primary failure, 1 secondary escape, and 2 therapeutic maintenances, whereas primary or secondary failure was observed under tocilizimub and TNF-blocking agents. Rituximab was the most prescribed (n = 9) and the most effective with a sustained response in 6 patients.

Conclusions

In rhupus refractory to conventional treatment, T or B lymphocytes targeted therapies, and particularly rituximab, seem to be a relevant therapeutic option unlike anticytokine biologics.