bluuebunny/crossref_metadata_2025 huggingface dataset:
Quality of YouTube videos for three common pediatric hip conditions: developmental hip dysplasia, slipped capital femoral epiphysis and Legg-Calve-Perthes disease
Authors: Lock Alistair M. , Baker Joseph F.
Published: March 2022

YouTube is an increasingly accessible platform for families to obtain health information from; however, it is unregulated. The aim of this article was to assess the quality, reliability and accuracy of YouTube videos related to three common pediatric hip conditions: development dysplasia of the hip (DDH), slipped capital femoral epiphysis (SCFE) and Legg-Calve-Perthes disease. YouTube was searched using a variety of keyword combinations. Videos were analysed using Journal of the American Medical Association, Global Quality Score and condition-specific scores created specifically for this study. Video duration and the number of views were also recorded. In total 120 videos were analysed, 40 for each of DDH, SCFE and Perthes disease. YouTube videos from physicians and academic institutions/hospitals are of significantly higher quality, reliability and accuracy than videos from patients, nonphysicians and commercial outlets. The higher quality for physician videos is associated with significantly longer video. Differences between the three pediatric orthopaedic conditions were not statistically significant. Videos of higher quality may be used as an adjunctive tool to strengthen clinical consultation. Parents and caregivers should be guided to videos from academic institutions or hospitals as a way of improving health literacy.
Top 100 cited studies in periacetabular osteotomy for acetabular dysplasia: do lower levels of evidence guide clinical practice?
Authors: Jeong Stacy H. , Samuel Linsen T. , Lu Elaine , Burkhart Robert J. , Acuña Alexander J. , Kamath Atul F.
Published: March 2022

As no prior study has examined the citations profile of key articles related to periacetabular osteotomy (PAO), our analysis utilized the Web of Science database to (1) identify the most-cited clinical studies relating to PAO in the management of acetabular dysplasia and (2) assess any trends over time with respect to the quality of literature. The top 100 highest-cited studies related to PAO had a mean of 49 citations (range, 6–666 per study). With respect to the level of evidence, most studies had level IV evidence (58%); 1% level I, 16% level II, 28% level III and 2% level V. Most studies were retrospective (n = 86); there were 14 prospective studies (including one randomized study). The most common study designs were case series (n = 58) and cohort (n = 16), followed by matched-cohort (n = 13) and case–control (n = 6). The mean ± SD Newcastle-Ottawa Scale score was 6.48 ± 1.31. A total of 59 and 41 of the included articles were classified as high risk and high quality, respectively. No studies were classified as very high risk. As a whole, our analysis demonstrated that currently available PAO literature is still of low quality and of low level of evidence. While PAO has been well-documented as a durable procedure for addressing acetabular dysplasia, future research must focus on higher quality, randomized and prospective data to answer key clinical or technique-related topics.
Is maternal employment site a source of exposure misclassification in studies of environmental exposures and birth outcomes? A simulation-based bias analysis of haloacetic acids in tap water and hypospadias
Authors: Zaganjor Ibrahim , Keil Alexander P. , Luben Thomas J. , Desrosiers Tania A. , Engel Lawrence S. , Reefhuis Jennita , Michalski Adrian M. , Langlois Peter H. , Olshan Andrew F. ,   The National Birth Defects Prevention Study
Published: March 2022

Background:

In population research, exposure to environmental contaminants is often indirectly assessed by linking residence to geocoded databases of environmental exposures. We explored the potential for misclassification of residence-based environmental exposure as a result of not accounting for the workplace environments of employed pregnant women using data from a National Birth Defects Prevention Study (NBDPS) analysis of drinking water haloacetic acids and hypospadias.

Methods:

The original analysis used NBDPS data from women with haloacetic acid exposure information in eight states who delivered an infant with second- or third-degree hypospadias (cases) or a male infant without a birth defect (controls) between 2000 and 2005. In this bias analysis, we used a uniform distribution to randomly select 11%–14% of employed women that were assumed to change municipal water systems between home and work and imputed new contaminant exposures for tap water beverages consumed at work among the selected women using resampled values from the control population. Multivariable logistic regression was used to estimate the association between hypospadias and haloacetic acid ingestion with the same covariates and exposure cut-points as the original study. We repeated this process across 10,000 iterations and then completed a sensitivity analysis of an additional 10,000 iterations where we expanded the uniform distribution (i.e., 0%, 28%).

Results:

In both simulations, the average results of the 10,000 iterations were nearly identical to those of the initial study.

Conclusions:

Our results suggest that household estimates may be sufficient proxies for worksite exposures to haloacetic acids in tap water.
Dosing for Personalized Prophylaxis in Hemophilia A Highly Varies on the Underlying Population Pharmacokinetic Models
Authors: Uster David W. , Chowdary Pratima , Riddell Anne , Garcia Cecilia , Aradom Elsa , Musarara Molly , Wicha Sebastian G.
Published: March 2022

Background:

Model-informed personalized prophylaxis with factor VIII (FVIII) replacement therapy aimed at higher trough levels is becoming indispensable for patients with severe hemophilia A. This study aimed to identify the most suitable population pharmacokinetic (PK) models for personalized prophylaxis using various FVIII products and 2 clinical assays and to implement the most suitable one in open-access software.

Methods:

Twelve published population PK models were systematically compared to predict the time above target (TaT) for a reference dosing occasion. External validation was performed using a 5-point PK data from 39 adult patients with hemophilia A with FVIII measured by chromogenic substrate (CSA) and 1-stage assays (OSAs) using NONMEM under 3 different conditions: a priori (with all FVIII samples blinded), a posteriori (with 1 trough sample), and general model fit (with all FVIII samples including the reference dosing occasion provided).

Results:

On average, the baseline covariate models overpredicted TaT (a priori; bias −3.8 hours to 49.6 hours). When additionally including 1 previous trough FVIII sample before the reference dosing occasion (a posteriori), only 50% of the models improved in bias (−1.0 hours to 36.5 hours) and imprecision (22.4 hours and 60.7 hours). Using all the time points (general model fit), the models accurately predicted (individual TaT less than ±12 hours compared with the reference) 62%–90% and 33%–74% of the patients using CSA and OSA data, respectively. Across all scenarios, predictions using CSA data were more accurate than those using the OSA data.

Conclusions:

One model performed best across the population (bias: −3.8 hours a priori, −1.0 hours a posteriori, and 0.6 hours general model fit) and acceptably predicted 44% (a priori) to 90% (general model fit) of the patients. To allow the community-based evaluation of patient–individual FVIII dosing, this model was implemented in the open-access model-informed precision dosing software “TDMx.”
Relationship of sleep disorders with long-term complications and health-related quality of life in people with well-controlled human immunodeficiency virus
Authors: Yoshino Yusuke , Wakabayashi Yoshitaka , Kitazawa Takatoshi
Published: March 2022

Although sleep disorders are common in patients with human immunodeficiency virus (HIV) infection, they have not been adequately evaluated under currently advanced treatments, mainly with integrase strand transfer inhibitors. However, the relationship of sleep disorders with long-term complications and quality of life (QOL) status in patients infected with HIV is still poorly understood. Such associations are important in the management of outpatients with HIV. Hence, this study aimed to evaluate these associations.

This cross-sectional observational study assessed the QOL changes of patients with HIV before and after the treatment regimen change. Male patients with well-controlled HIV who attended our hospital and changed HIV medications for reasons other than treatment failure between October 2019 and September 2021 were included. At the time of regimen change, sleep disorder status was assessed according to the Pittsburgh sleep quality index (PSQI), and health-related QOL (HRQOL) was assessed using the medical outcomes study 8-item short form health survey. In addition, we collected information on age, blood tests, and long-term comorbid conditions present during the evaluation. The HIV treatment regimen was also reviewed.

Out of 45 male Japanese patients with HIV that were included in this study, 24 (53.3%) and 21 (46.7%) were classified into the sleep disorder group and nonsleep disorder group, respectively, according to their PSQI scores. The sleep disorder group had a significantly lower HRQOL mental component summary (P = .0222) than the nonsleep disorder group. The prevalence rates of hypertension, dyslipidemia, and diabetes mellitus were not significantly different between the 2 groups. In addition, a significant correlation was observed between PSQI scores and the HRQOL status (mental component summary, P = .0450; physical component summary, P = .0350).

Sleep disorders remain common in patients with well-controlled HIV infection receiving current treatment. Sleep disorder is significantly associated with a low HRQOL in these patients. Hence, sleep status evaluation is necessary to improve HIV management.
Assessment of quality of life and activities of daily living among elderly patients with hypertension and impaired physical mobility in home health care by antihypertensive drugs plus acupuncture
Authors: Huang Kuei-Yu , Chang Ching-Hao , Yu Kai-Chiang , Hsu Chung-Hua
Published: March 2022

Background:

To evaluate the efficacy of acupuncture in improving quality of life (QOL) and activities of daily living among elderly patients with hypertension and impaired physical mobility in home health care.

Methods:

Seventy participants were allocated randomly to receive either acupuncture together with antihypertensive drugs (n = 35) or antihypertensive drugs only (n = 35). Acupuncture was conducted twice a week for 12 consecutive weeks, each lasting 30 minutes. Acupuncture points San Yin Jiao, Xue Hai, Taichong, Zusanli, and Hegu acupuncture points were used bilaterally. The primary outcome was change in QOL score, evaluating by Short-Form 36 Item Health Survey (SF-36). Secondary outcomes were changes in Barthel index score and blood pressure. Besides, pain evaluation by Visual analog scale, among acupuncture and control subgroups in participants with diagnosis with disease of the musculoskeletal system and connective tissue (ICD-9: 710-739).

Results:

Thirty-one participants in each of the acupuncture group and the control group completed the study. After 12 weeks of treatment, compared with the control group, the combination of antihypertensive treatments and acupuncture helped to improve bodily pain (P= .03), physical component summary (P= .04), mental health (P< .001), mental component summary (P= .008), Barthel index (P= .02), and systolic blood pressure (P= .01). In contrast, the control group showed no significant changes. Change in pain score revealed that there were a significant between-group differences after 6weeks (P= .01) and 12weeks of treatment (P= .001).

Conclusion:

The results of the study suggested that in home health care elderly patients with hypertension and impaired physical mobility, antihypertensive drugs combined with acupuncture therapy will be more beneficial to improve QOL, activities of daily living, and blood pressure.
Construction of miRNA-regulated drug-pathway network to screen drug repurposing candidates for multiple sclerosis
Authors: Kong Xiaotong , Wang Jianjian , Cao Yuze , Lu Xiaoyu , Zhang Huixue , Zhang XiaoMing , Bo Chunrui , Bai Ming , Li Shuang , Jiao Yang , Wang Lihua
Published: March 2022

Given the high disability rate of multiple sclerosis (MS), there is a need for safer and more effective therapeutic agents. Existing literature highlights the prominent roles of miRNA in MS pathophysiology. Nevertheless, there are few studies that have explored the usefulness of existing drugs in treating MS through potential miRNA-modulating abilities.

The current investigation identifies genes that may exacerbate the risk of MS due to their respective miRNA associations. These findings were then used to determine potential drug candidates through the construction of miRNA-regulated drug-pathway network through genes. We uncovered a total of 48 MS risk pathways, 133 MS risk miRNAs, and 186 drugs that can affect these pathways. Potential MS risk miRNAs that are also regulated by therapeutic candidates were hsa05215 and hsa05152. We analyzed the properties of the miRNA-regulated drug-pathway network through genes and uncovered a number of novel MS agents by assessing their respective Z-values.

A total of 20 likely drug candidates were identified, including human immunoglobulin, aspirin, alemtuzumab, minocycline, abciximab, alefacept, palivizumab, bevacizumab, efalizumab, tositumomab, minocycline, etanercept, catumaxomab, and sarilumab. Each of these agents were then explored with regards to their likely mechanism of action in treating MS.

The current investigation provides a fresh perspective on MS biological mechanisms as well as likely treatment strategies.
A holistic investigation of the global outcomes of spontaneous pneumothorax during 1980-2021, including the COVID-19 pandemic A bibliometric approach
Authors: Baldemir Ramazan , Ülger Gulay
Published: March 2022

Background:

During coronavirus pandemic, despite the increase in the number of studies on spontaneous pneumothorax (SP), there is not enough bibliometric study in the literature. In this study, it was aimed to analyze scientific articles published on SP.

Methods:

Studies published on SP between 1980 and 2021 were obtained from the Web of Science database and analyzed using statistical and bibliometric methods. Spearman correlation coefficient was used for correlation studies. The exponential smoothing estimator was used to forecast publication trend for coming years. Network visualization maps were used to analyze citations and identify trending topics.

Results:

A total of 2422 publications were found. 1403 (57.9%) of these publications were articles. The articles on SP have increased with a non-linear trend in recent years. The top 5 contributors to the literature were USA (231, 16.4%), Japan (161, 11.4%), United Kingdom (98, 6.9%), France (81, 5.7%), and Taiwan (78, 5.5%). The top 3 most active institutions were National Taiwan University Hospital (22, 1.5%), Catholic University Korea (19, 1.3%), and National Taiwan University (19, 1.3%). The top 3 journals that published the most articles were Chest (51), Annals of Thoracic Surgery (46), and Journal of Thoracic Disease (45). The most studied subjects were primary SP, recurrence, thoracoscopy, pleurodesis, video-assisted thoracoscopic surgery, COVID-19, video-assisted thoracic surgery, chest tube(s), and secondary spontaneous pneumothorax. According to trend topics analysis, the keywords studied in recent years are COVID-19, chest tubes, pneumonia, subcutaneous emphysema, risk factors, dyspnea, primary SP, FLCN gene, tension pneumothorax, uniportal, postoperative recurrence, secondary spontaneous pneumothorax, chronic obstructive pulmonary disease, and uniportal.

Conclusion:

In this comprehensive bibliometric study, we summarized 1403 articles about SP, which has an increasing trend in the number of articles during the COVID-19 pandemic process. This article can be a useful resource for clinicians and scientists through presenting a summary of worldwide studies related to SP, including the ones during COVID-19 pandemic.
Time to Reflect and Take Action on Health Disparities and Health Inequities
Authors: Salmond Susan , Dorsen Caroline
Published: March 2022

The United States healthcare system underperforms in healthcare access, quality, and cost resulting in some of the poorest health outcomes among comparable countries, despite spending more of its gross national product on healthcare than any other country in the world. Within the United States, there are significant healthcare disparities based on race, ethnicity, socioeconomic status, education level, sexual orientation, gender identity, and geographic location. COVID-19 has illuminated the racial disparities in health outcomes.

This article provides an overview of some of the main concepts related to health disparities generally, and in orthopaedics specifically. It provides an introduction to health equity terminology, issues of bias and equity, and potential interventions to achieve equity and social justice by addressing commonly asked questions and then introduces the reader to persistent orthopaedic health disparities specific to total hip and total knee arthroplasty.
Vasoplegic Shock Represents a Dominant Hemodynamic Profile of Multisystem Inflammatory Syndrome Following COVID-19 in Children and Adolescents
Authors: Alali Alexander , O’Neil Erika , Anders Marc , Abella Jayvee , Shekerdemian Lara S. , Vogel Tiphanie P. , Sexson Tejtel Kristen , Tume Sebastian C.
Published: March 2022

OBJECTIVES:

The hemodynamic profile of multisystem inflammatory syndrome in children (MIS-C)–related shock remains poorly defined and, therefore, challenging to support with pharmacotherapy in the ICU. We aimed to evaluate the hemodynamic profile and vasoactive medication management used in MIS-C patients presenting to the ICU in shock and provide data from high-fidelity continuous cardiac output monitoring.

DESIGN

Single-center retrospective case-cohort study.

SETTING:

Pediatric and cardiac ICU in a quaternary-care hospital.

PATIENTS:

All patients who met U.S. Centers for Disease Control and Prevention criteria for MIS-C and who were admitted to the ICU between March 2020 and May 2021 required vasoactive support and were placed on continuous cardiac index (CCI) monitoring. Patients requiring extracorporeal life support were excluded.

INTERVENTIONS:

None.

MEASUREMENTS AND MAIN RESULTS:

Among 52 children with MIS-C presenting in shock and requiring vasoactive support, 14 patients (27%) were placed on CCI monitoring. These 14 patients had hyperdynamic cardiac index (CI) and low indexed systemic vascular resistance (SVRi) in the first 24 hours with normalization of CI and improved SVRi within the subsequent 24 hours.

CONCLUSIONS:

Further studies are needed to evaluate the difference between the use of vasoconstrictor versus vasodilators in pediatric patients with MIS-C because a phenotype with high CI and low SVRi may be important.
Education for Pediatric Gastroenterology Pathology Reports Increases Understanding Ahead of 21st Century Cures Act Rollout
Authors: Dunwoodie Leland , Vannilam Annette
Published: March 2022

Background:

As a result of the 21st Century Cures Act, Pediatric Gastroenterology (Peds GI) patients and caregivers are receiving pathology reports directly on their online patient portal. This quality improvement project attempted to validate an educational handout about Peds GI pathology reports and identify areas for caregiver education.

Methods:

Caregivers (n = 59) of patients undergoing Peds GI procedures were surveyed about their knowledge of pathology reports. Caregivers’ responses to each of 4 questions were assessed before and after reading an educational handout. These 4 questions questioned the contents and creators of pathology reports, the role of pathologists, and caregiver confidence in interpreting pathology reports.

Results:

Nearly one-third of caregivers did not know the role of pathologists before education, and one-fifth of caregivers did not know the contents of a pathology report. Caregivers with less than a college degree (n = 21, P = 0.0089), and caregivers of patients undergoing their first procedure (n = 27, P = 0.0022) showed a significant improvement in responses after the educational handout.

Conclusions:

Educational handouts can increase caregiver understanding of pathology reports, especially for those with lower education levels or those with children undergoing their first procedure.
Musculoskeletal Tuberculosis
Authors: Chapuis Elisa , Benali Khadija , Silbermann-Hoffman Olivia , Berleur Marie , Ottaviani Sébastien , van Gysel Damien , Goulenok Tiphaine , Papo Thomas , Sacre Karim
Published: March 2022

Background/ Objective

Skeletal tuberculosis (TB) is rare. We aimed to report on diagnostic strategy and treatment of skeletal TB.

Methods

In this multidisciplinary single-center medical records review study, all adult patients admitted between January 2009 and December 2019 with microbiologically proven skeletal TB were included. Demographic, medical history, laboratory, imaging, pathologic findings, treatment, and follow-up data were extracted from medical records.

Results

Among 184 patients identified with TB, 21 (16 women, 42 years [27, 48 years]) had skeletal involvement. Skeletal TB included spondylitis (n = 11), lytic bone lesions (n = 7), sacroiliitis (n = 5), arthritis (n = 3), osteitis (n = 2), and diffuse muscle abscesses without bone lesion (n = 1). Lytic lesions involved both axial and peripheral skeleton at multiple sites in most cases. 18F-fluorodeoxyglucose positron emission tomography was performed in 13 patients and helped to detect multifocal asymptomatic lesions and to target biopsy. All patients were treated with anti-TB therapy for 7 to 18 months. Fifteen patients (71.4%) received steroids as an adjunct therapy. Eleven patients needed an orthopedic immobilization corset, and 3 patients underwent surgery. All patients clinically improved under treatment, but 2 relapsed over a median follow-up of 24 months (12–30 months). No patient died or suffered long-term disabilities.

Conclusion

Our study emphasizes the diversity of skeletal involvement in TB. 18F-fluorodeoxyglucose positron emission tomography scanner at diagnosis is key to assess the extension of skeletal involvement and guide extraskeletal biopsy. Neurological complications might be prevented by adding corticosteroids to anti-TB therapy.
Impact of a Musculoskeletal “Mini-Residency” Professional Development Program on Knee Magnetic Resonance Imaging Orders by Primary Care Providers
Authors: Mulcaire-Jones Erica , Barker Andrea M. , Beck J. Peter , Lawrence Phillip , Cannon Grant W. , Battistone Michael J.
Published: March 2022

Background

The US Department of Veterans Affairs has created a portfolio of educational programs to train primary care providers (PCPs) in the evaluation and management of common musculoskeletal (MSK) conditions. Appropriate resource utilization for evaluation of knee pain, including limiting unnecessary magnetic resonance imaging (MRI) studies, is an important theme of these initiatives. The objective of this study was to report the utilization of knee MRI by PCP providers before and after the MSK education program and to determine the appropriateness of these MRI orders.

Methods

Twenty-six PCPs participated in the MSK Mini-Residency educational program held in Salt Lake City between April 2012 and October 2014. Knee MRI orders submitted by these providers 12 months before and 12 months after their participation were reviewed. Magnetic resonance imaging orders were categorized as “inappropriate,” “probably inappropriate,” or “possibly appropriate,” based on accepted guidelines for knee MRI utilization. Differences in the numbers of precourse and postcourse MRI orders for each of these categories were compared using Student t test.

Results

Following our program, MRI orders decreased from 130 (precourse) to 93 (postcourse), a reduction of 28% (p = 0.04). This reduction was observed entirely within the “inappropriate” and “probably inappropriate” categories; the number of orders categorized as “possibly appropriate” increased, but not significantly.

Conclusions

The MSK Mini-Residency training program was a successful educational intervention and was associated with a reduction in inappropriate knee MRI utilization for some participants, while keeping appropriate MRI utilization stable.
Data Resources for Evaluating the Economic and Financial Consequences of Surgical Care in the United States
Authors: Scott John W. , Ayoung-Chee Patricia , Lester Erica L.W. , Bruns Brandon R. , Davis Kimberly A. , Gore Amy , Knowlton Lisa Marie , Liu Charles , Martin R. Shayn , Oh Esther Jiin , Ross Samuel Wade , Wandling Michael , Minei Joseph P. , Staudenmayer Kristan ,   on behalf of the AAST Healthcare Economics Subcommittee
Published: March 2022

Evaluating the relationship between healthcare costs and quality is paramount in the current healthcare economic climate, as an understanding of value is needed to drive policy decisions. While many policy analyses are focused on the larger healthcare system, there is a pressing need for surgically-focused economic analyses. Surgical care is costly, innovative technology is constantly introduced into the operating room, and surgical care impacts patients’ short- and long-term physical and economic wellbeing. Unfortunately, significant knowledge gaps exist regarding the relationship between cost, value, and economic impact of surgical interventions. Despite the plethora of healthcare data available in the forms of claims databases, discharge databases, and national surveys, no single source of data contains all the information needed for every policy-relevant analysis of surgical care. For this reason, it is important to understand which data are available and what can be accomplished with each of the datasets. In this article, we provide an overview of databases commonly used in surgical health services research. We focus our review on the following five categories of data: governmental claims databases, commercial claims databases, hospital-based clinical databases, state and national discharge databases, and national surveys. For each, we present a summary of the database sampling frame, clinically relevant variables, variables relevant to economic analyses, strengths, weaknesses, and examples of surgically-relevant analyses. This review is intended to improve understanding of the current landscape of data available as well as stimulate novel analyses among surgical populations. Ongoing debates over national health policy reforms may shape the delivery of surgical care for decades to come. Appropriate use of available data resources can improve our understanding of the economic impact of surgical care on our health care system and our patients.

Level of Evidence

V
Tranexamic acid is not inferior to placebo with respect to adverse events in suspected traumatic brain injury patients not in shock with a normal head computed tomography scan: A retrospective study of a randomized trial
Authors: Harmer Jordan W. , Dewey Elizabeth N. , Meier Eric N. , Rowell Susan E. , Schreiber Martin A.
Published: March 2022

BACKGROUND

A 2-g bolus of tranexamic acid (TXA) has been shown to reduce 28-day mortality in a randomized controlled trial. This study investigates whether out-of-hospital TXA use is associated with adverse events or unfavorable outcomes in suspected traumatic brain injury (TBI) when intracranial hemorrhage (ICH) is absent on initial computed tomography.

METHODS

This study used data from a 2015 to 2017, multicenter, randomized trial studying the effect of the following TXA doses on moderate to severe TBI: 2-g bolus, 1-g bolus plus 1-g infusion over 8 hours, and a placebo bolus with placebo infusion. Of the 966 participants enrolled, 395 with an initial computed tomography negative for ICH were included in this analysis. Fifteen adverse events (28-day incidence) were studied: myocardial infarction, deep vein thrombosis, seizure, pulmonary embolism, acute respiratory distress syndrome, cardiac failure, liver failure, renal failure, cerebrovascular accident, cardiac arrest, cerebral vasospasm, “any thromboembolism,” hypernatremia, acute kidney injury, and infection. Other unfavorable outcomes analyzed include mortality at 28 days and 6 months, Glasgow Outcome Scale—Extended score of ≤4 at discharge and 6 months, intensive care unit–free days, ventilator-free days, hospital-free days, and combined unfavorable outcomes. In both study drug groups, the incidence of dichotomous outcomes and quantity of ordinal outcomes were compared with placebo.

RESULTS

No statistically significant increase in adverse events or unfavorable outcomes was found between either TXA dosing regimen and placebo. Demographics and injury scores were not statistically different other than two methods of injury, which were overrepresented in the 1-g TXA bolus plus 1-g TXA infusion.

CONCLUSION

Administration of either a 2-g TXA bolus or a 1-g TXA bolus plus 1-g TXA 8-hour infusion in suspected TBIs without ICH is not associated with increased adverse events or unfavorable outcomes. Because the out-of-hospital 2-g bolus is associated with a mortality benefit, it should be administered in suspected TBI.

LEVEL OF EVIDENCE

Therapeutic/Care Management; Level II.
Predominance of community-associated, methicillin-susceptible Staphylococcus aureus infections among hospitalized children and adolescents
Authors: Tsirigotaki Maria , Giormezis Nikolaos , Maraki Sofia , Spiliopoulou Iris , Galanakis Emmanouil
Published: March 2022

Introduction.

Staphylococcus aureus

infections cause significant morbidity and mortality in children and adolescents.

Gap Statement. There is limited data on the characteristics of

S. aureus

infections requiring hospitalization in childhood.

Aim.To investigate the molecular epidemiology and antibiotic resistance of

S. aureus

clinical isolates from children and adolescents.

Methodology.All

S. aureus

isolates recovered from patients aged <18 years, admitted to a referral hospital, with culture-proven invasive or non-invasive infections during the 4 year period 2015 to 2018 were analysed for antimicrobial resistance, virulence genes, PFGE and multilocus sequence typing (MLST). Cases were assigned to community-associated, community-onset healthcare-associated or hospital-associated infections based on epidemiological case definitions.

Results.Among 139 

S. aureus

infections, 88.5 % (123/139) were caused by methicillin-susceptible isolates (MSSA) and 73.4 % (102/139) were classified as community-associated infections. tst and lukS/lukF-PV genes were more common among MRSA as compared to MSSA isolates (tst, p 0.04; lukS/lukF-PV, p 0.007). Invasive disease was noted in 22/139 patients (15.8 %). Staphylococcal scalded skin syndrome caused by fusidic-resistant MSSA increased over time (22.8 % in 2017–2018 vs 8.3 % in 2015–2016, OR 3.24; 95 % CI 1.10–8.36; P 0.03). By PFGE genotyping, 22 pulsotypes were identified. A total of five sequence types (STs) were identified among 58 isolates analysed by MLST. More than one third of MSSA isolates (40/123, 32.5 %) and 13/23 (56.5 %) of SSSS isolates belonged to pulsotype 1, classified as sequence type 121 (ST121). MRSA isolates were equally distributed to pulsotypes A (ST30), B (ST239), C (ST80), H (ST225). ST121 isolates carried fnbA (40/40), eta/etb genes (29/40), exhibited high resistance to fusidic acid and were increasingly resistant to mupirocin.

Conclusion.In our population, community-associated MSSA was the predominant cause of

S. aureus

infections characterized by polyclonality, increasing resistance to fusidic acid and mupirocin. PFGE type 1 ST121 clone, harboured exfoliative toxin genes and was associated with rising trends of SSSS.
Nationwide Effectiveness of First and Second SARS-CoV2 Booster Vaccines during the Delta and Omicron Pandemic Waves in Hungary (HUN-VE 2 Study)
Authors: Kiss Zoltán , Wittmann István , Polivka Lőrinc , Surján György , Surján Orsolya , Barcza Zsófia , Molnár Gergő Attila , Nagy Dávid , Müller Veronika , Bogos Krisztina , Nagy Péter , Kenessey István , Wéber András , Pálosi Mihály , Szlávik János , Schaff Zsuzsa , Szekanecz Zoltán , Müller Cecília , Kásler Miklós , Vokó Zoltán
Published: March 2022

Background

In Hungary, the pandemic waves in late 2021 and early 2022 were dominated by the Delta and Omicron SARS-CoV-2 variants, respectively. Booster vaccines were offered with one or two doses for the vulnerable population during these periods.

Methods and Findings

The nationwide HUN-VE 2 study examined the effectiveness of primary immunization, single booster, and double booster vaccination in the prevention of Covid-19 related mortality during the Delta and Omicron waves, compared to an unvaccinated control population without prior SARS-CoV-2 infection during the same study periods.

The risk of Covid-19 related death was 55% lower during the Omicron vs. Delta wave in the whole study population (n=9,569,648 and n=9,581,927, respectively; rate ratio [RR]: 0.45, 95% confidence interval [CI]: 0.44–0.48). During the Delta wave, the risk of Covid-19 related death was 74% lower in the primary immunized population (RR: 0.26; 95% CI: 0.25–0.28) and 96% lower in the booster immunized population (RR: 0.04; 95% CI: 0.04–0.05), vs. the unvaccinated control group. During the Omicron wave, the risk of Covid-19 related death was 40% lower in the primary immunized population (RR: 0.60; 95% CI: 0.55–0.65) and 82% lower in the booster immunized population (RR: 0.18; 95% CI: 0.16–0.2) vs. the unvaccinated control group. The double booster immunized population had a 93% lower risk of Covid-19 related death compared to those with only one booster dose (RR: 0.07; 95% CI. 0.01–0.46). The benefit of the second booster was slightly more pronounced in older age groups.

Conclusions

The HUN-VE 2 study demonstrated the significantly lower risk of Covid-19 related mortality associated with the Omicron vs. Delta variant and confirmed the benefit of single and double booster vaccination against Covid-19 related death. Furthermore, the results showed the additional benefit of a second booster dose in terms of SARS-CoV-2 infection and Covid-19 related mortality.
Feeding practices and cost of diet of six-month-old HIV exposed uninfected compared to HIV unexposed uninfected infants in a peri-urban community in South Africa
Authors: Nyofane Mothusi , Hoffman Marinel , Botha Tanita , Feucht Ute
Published: March 2022

Background

The increasing population of HIV-exposed-uninfected (HEU) infants are known to be at risk of poor nutritional status and suboptimal growth, with biological risk factors implicated, yet the cost to families of feeding infants is often overlooked.

Objective

The study compared the infant feeding practices and costs and macronutrient intake of HEU vs HIV-unexposed-uninfected (HUU) six-month-old infants in the Gauteng Province of South Africa.

Methods

A cross-sectional study investigated 46 HEU and 55 HUU infants aged six months and utilised a single quantified 24-hr recall and the FoodFinder™ program for meal analysis. The estimation of diet cost utilised supermarket food prices based on the 24-hr recall method.

Results

Mothers of HEU infants had significantly lower income (p<0.01) and educational attainment (p=0.03). The infant feeding practices differed between HEU vs HUU infants (p=0.05): exclusive breastfeeding (50.0% vs 34.0%) and mixed breastfeeding (38.1% vs 64.2%). Common complementary foods for HEU versus HUU infants included commercial infant cereals (CIC) (48.7% vs 70.9%; p=0.04); fruits and vegetables (33.3% vs 15.7%; p=0.05) and maize meal porridge (25.6% vs 15.7%; p=0.24), respectively. The mean daily cost of diet of HEU vs HUU infants was 8.55±7.35ZAR ($0.68±0.59USD) vs 10.97±7.92ZAR($0.88±0.63 USD); (p=0.10). Regarding the complementary feeding, there were non-significant differences in protein, fat, and carbohydrate intakes (p>0.05) and their costs per daily intake (p>0.05) between the groups.

Conclusion

There are no significant differences in cost, feeding and macronutrient intakes between HEU and HUU. Suboptimal breastfeeding practices remains an issue within the first six months. More sustained effort is required to support and promote exclusive breastfeeding.
Age and product dependent vaccine effectiveness against SARS-CoV-2 infection and hospitalisation among adults in Norway: a national cohort study, July – November 2021
Authors: Starrfelt Jostein , Danielsen Anders Skyrud , Buanes Eirik Alnes , Juvet Lene Kristine , Lyngstad Trude Marie , Isaksson Rø Gunnar Øyvind , Veneti Lamprini , Watle Sara Viksmoen , Meijerink Hinta
Published: March 2022

Background

COVID-19 vaccines have been crucial in the pandemic response and understanding changes in vaccines effectiveness is essential to guide vaccine policies. Though the Delta variant is no longer dominant, understanding vaccines effectiveness properties will provide essential knowledge to comprehend the development of the pandemic and estimate potential changes over time.

Methods

In this population-based cohort study, we estimated vaccine effectiveness against SARS-CoV-2 infections, hospitalisations, intensive care admissions, and death using Cox proportional hazard models, across different vaccine product regimens and age groups, between 15 July and 31 November 2021 (Delta variant period). Vaccine status is included as a time-varying covariate and all models were adjusted for age, sex, comorbidities, county of residence, country of birth, and living conditions. Data from the entire adult Norwegian population were collated from the National Preparedness Register for COVID-19 (Beredt C19).

Results

The overall adjusted vaccine effectiveness against infection decreased from 81.3% (confidence interval (CI): 80.7 to 81.9) in the first two to nine weeks after receiving a second dose to 8.6% (CI:4.0 to 13.1) after more than 33 weeks, compared to 98.6% (CI: 97.5 to 99.2) and 66.6% (CI: 57.9 to 73.6) against hospitalisation respectively. After the third dose (booster), the effectiveness was 75.9% (CI: 73.4 to 78.1) against infection and 95.0% (CI: 92.6 to 96.6) against hospitalisation. Spikevax or a combination of mRNA products provided the highest protection, but the vaccine effectiveness decreased with time since vaccination for all vaccine regimens.

Conclusions

Even though the vaccine effectiveness against infection wanes over time, all vaccine regimens remained effective against hospitalisation after the second vaccine dose. For all vaccine regimens, a booster facilitated recovery of effectiveness. The results from this support the use of heterologous schedules, increasing flexibility in vaccination policy.

Funding

no external funding
Reproductive health needs of Human papillomavirus (HPV) Positive women: A systematic review
Authors: Galeshi Mina , Shirafkan Hoda , Yazdani Shahla , Motaghi Zahra
Published: March 2022

Background

Human papillomavirus is one of the most important transmitted viruses that causes of cervical cancer.

In women undergoing cervical screening, it is important to be aware of ways to reduce anxiety. The present systematic review conducted to determine the reproductive health needs of women with HPV.

Methods

In this systematic review, articles without time constraints searched in PubMed, Scopus, Web of Science, Google Scholar and Iranian Magiran, SID and Iranmedex.

Keywords used: HPV, Information, Want, Need, Know, etc. and their Persian equivalents in the title and abstract of the articles.

Papers after identification by two researchers Contradictions evaluated and discussed with the third author.

Results

At first 1056articles retrieved which after removing,13articles published between2004-2021were entered. The studies were qualitative(N=9),quantitative(N=3), and one was unclear.Most qualitative studies collected data using individual interviews(N=7), two qualitative studies, narratives of HPV patients from a website of patient experiences and questions. The quality evaluation showed that good=8, Average=2, and one was of poor. There is not enough information about Friedman AL etal and Garland SM articles to check the quality, but since these studies were valuable, they included in the study according to the opinion of the research team.

Conclusion

Surveys showed that the majority of women had unanswered questions about their HPV test results. The information that women thought was helpful in interpreting their test results included having a high-risk type of HPV, the risk of short-term and long-term cancer, and cancer survival statistics for the virus. Women also needed information about sexual transmission, how HPV tested positive in a long-term relationship, and the potential consequences for their partners and the risk of re-infection. Younger women had questions about whether HPV could affect fertility.
The complex relationship of air pollution and neighborhood socioeconomic deprivation and their association with cognitive decline
Authors: Christensen Grace , Li Zhenjiang , Pearce John , Marcus Michele , Lah James J. , Waller Lance A. , Ebelt Stefanie , Huels Anke
Published: March 2022

Background

Air pollution and neighborhood socioeconomic status (nSES) have been shown to affect cognitive decline in older adults. In previous studies, nSES acts as both a confounder and an effect modifier between air pollution and cognitive decline.

Objectives

This study aims to examine the individual and joint effects of air pollution and nSES on cognitive decline on adults 50 years and older in Metro Atlanta, USA.

Methods

Perceived memory and cognitive decline was assessed in 11,897 participants aged 50+ years from the Emory Healthy Aging Study (EHAS) using the cognitive function instrument (CFI). Three-year average air pollution concentrations for 12 pollutants and 16 nSES characteristics were matched to participants using census tracts. Individual exposure linear regression and LASSO models explore individual exposure effects. Environmental mixture modeling methods including, self-organizing maps (SOM), Bayesian kernel machine regression (BKMR), and quantile-based G-computation explore joint effects, and effect modification between air pollutants and nSES characteristics on cognitive decline.

Results

Participants living in areas with higher air pollution concentrations and lower nSES experienced higher CFI scores (beta: 0.121; 95% CI: 0.076, 0.167) compared to participants living in areas with low air pollution and high nSES. Additionally, the BKMR model showed a significant overall mixture effect on cognitive decline, indicating synergy between air pollution and nSES. These joint effects explain protective effects observed in single-pollutant linear regression models, even after adjustment for confounding by nSES (e.g., an IQR increase in CO was associated with a 0.038-point decrease (95% CI: -0.06, -0.01) in CFI score).

Discussion

Observed protective effects of single air pollutants on cognitive decline can be explained by joint effects and effect modification of air pollutants and nSES. Researchers must consider nSES as an effect modifier if not a co-exposure to better understand the complex relationships between air pollution and nSES in urban settings.
Prediction of gestational diabetes mellitus using early oral glucose tolerance test
Authors: Kandauda C. , Manathunga S.S , Abeyagunawardena I.A , Thilakarathne K.M.H.C
Published: March 2022

Introduction

Gestational Diabetes Mellitus (GDM) is defined as diabetes first detected at the second or third trimester of pregnancy, excluding preexisting diabetes. We aimed to build a predictive model of GDM using booking oral glucose tolerance test (OGTT) values.

Materials and Methods

Seventy-five healthy mothers who underwent 75g OGTT at 12-14 weeks and at 24-28 weeks were recruited. GDM was diagnosed at 28 weeks by cutoffs proposed by the Hyperglycemia and Adverse Pregnancy Outcomes study.

Sensitivities and specificities for diagnosing GDM using different cut-offs for each of the three booking OGTT variables were measured. A series of multivariate binary logistic regression models were fitted using different combinations of the three booking OGTT variables. In-sample sensitivities and specificities for different cutoff probabilities of the models were calculated and Receiver Operating Characteristic (ROC) curves were constructed. The Area Under the Curve (AUC) of the ROC curve and the best cutoff value which maximized the sum of sensitivity and specificity of each model were computed.

Results

AUC of ROC curves for isolated fasting, 1 hour and 2 hour booking OGTT values for the prediction of GDM were 69.8%, 67.1% and 61.0% respectively. However, the logistic regression model with fasting and 1 hour booking OGTT values as predictors out-performed all other models with an AUC of 76.3%, in-sample sensitivity of 87.5% and a negative predictive value of 95.12%.

Conclusions

The future occurrence of GDM can be predicted utilizing a logistic model with fasting and 1 hour booking OGTT variables, which enables early identification and intervention.
A high-throughput 384-well CometChip platform reveals a role for 3-methyladenine in the cellular response to etoposide-induced DNA damage
Authors: Li Jianfeng , Beiser Alison , Dey Nupur B. , Takeda Shunichi , Saha Liton Kumar , Hirota Kouji , Parker L. Lynette , Carter Mariah , Arrieta Martha I. , Sobol Robert W.
Published: March 2022

The Comet or single-cell gel electrophoresis assay is the gold standard for analysis of cellular, nuclear genome damage. However, low throughput limits its application for large-scale studies. To overcome these limitations, a 96-well CometChip platform was recently developed that increases throughput and reduces variation due to simultaneous processing and automated analysis of 96 samples. To advance throughput further, we developed a 384-well CometChip platform that allows analysis of ∼100 cells per well. The 384-well CometChip extends the capacity by 4-fold as compared to the 96-well system, enhancing application for larger DNA damage analysis studies. The overall sensitivity of the 384-well CometChip is consistent with that of the 96-well system, sensitive to genotoxin exposure and to loss of DNA repair capacity. We then applied the 384-well platform to screen a library of protein kinase inhibitors to probe each as enhancers of etoposide induced DNA damage and found that 3-methyladenine significantly increased levels of etoposide-induced DNA damage. Our results suggest that a 384-well CometChip is useful for large-scale DNA damage analyses, which may have increased potential in the evaluation of chemotherapy efficacy, compound library screens, population-based analyses of genome damage and evaluating the impact of environmental genotoxins on genome integrity.