bluuebunny/crossref_metadata_2025 huggingface dataset:
Investigation of hub genes involved in Turner syndrome using biological informatics methods
Authors: Cheng Tiantian , Li Xiaoli , Chen Jinhu , Yang Linlin , Liu Jing , Song Guangyao , Ma Huijuan
Published: March 2022

Background:

This study aimed to explore candidate genes and their potential interaction mechanism critical to the pathophysiology of Turner syndrome by using the Gene Expression Omnibus database.

Methods:

GSE58435 data set was obtained by querying the Gene Expression Omnibus database. Differentially expressed genes (DEGs) were screened using R and subsequently annotated by Gene Ontology. Functional enrichment analysis was performed based on the Kyoto Encyclopedia of Genes and Genomes database for annotation, visualization, and integrated discovery. A protein-protein interaction network of different genes was constructed based on the STRING database, in which hub genes were explored through Cytoscape software. The expression of the hub genes was verified by analyzing the gene expression in the GSE46687 data set.

Results:

A total of 733 differential genes were identified. These differentially expressed genes were significantly enriched in nucleoplasm and nucleus. Their molecular function was concentrated on DNA binding and transcription, coronary artery, and adipose tissue development. According to the annotation of Kyoto Encyclopedia of Genes and Genomes, the identified DEGs were mainly enriched in inflammatory mediator regulation of TRP channels, osteoclast differentiation. A total of 10 hub genes (HIST1H2BA, TRIM71, HIST1H2BB, HIST1H4D, TNF, TP53BP1, CDCA8, EGF, HMG20B, and BCL9) were identified from the constructed protein-protein interaction network. These genes were discovered to be highly expressed in osteoclasts, ovaries, digestive tract, blood, and lymphatic tissues through the online application of human protein atlas.

Conclusion:

In this study, 733 DEGs and 10 hub genes were identified. They would be new candidate targets in Turner syndrome.
The efficacy and safety of yukmijihwang-hwan (Liuweidihuang-wan) for type 2 diabetes mellitus without complications
Authors: Baek Jisoo , Kim Jinmi , Shin Seonmi , Cho Chungsik
Published: March 2022

Background:

This systematic review and meta-analysis of randomized controlled trials (RCTs) will aim to assess the efficacy and safety of Yukmijihwang-hwan for type 2 diabetes without complications.

Methods:

To identify eligible studies, we will perform a systematic search of the following electronic databases: MEDLINE (PubMed), EMBASE, the Cochrane Central Register of Controlled Trials, China National Knowledge Infrastructure, Citation Information by NII, Korean Information Service System, Korean Medical Database, Oriental Medicine Advanced Searching Integrated System, and ScienceON. Search terms will include “Type 2 Diabetes” for participants as well as “Yukmijihwang-tang” or “Liuwei dihuang tang” for interventions. Two independent researchers will perform data extraction and assessment using Cochrane’s risk of bias tool, with disagreements being resolved through discussions with a third researcher.

Results:

This study will evaluate the antidiabetic effects of Yukmijihwang-hwan from 3 perspectives (blood glucose level, insulin resistance, and β-cell function) as well as its safety by reviewing the reported adverse effects.

Conclusion:

This systematic review will provide evidence regarding the antidiabetic efficacy and safety of Yukmijihwang-tang in type 2 diabetes mellitus.
Comparison of dobutamine and levosimendan for treatment of sepsis-induced cardiac dysfunction
Authors: Guo Jun , Zhang Xianhuan , Zhu Yanan , Cheng Qiong
Published: March 2022

Background:

Levosimendan and dobutamine are extensively used to treat sepsis-induced cardiomyopathy. Previous studies on whether levosimendan is superior to dobutamine are still controversial. We performed a protocol for systematic review and metaanalysis to compare the efficacy and safety of levosimendan versus dobutamine for the treatment of sepsis-induced cardiomyopathy.

Methods:

This protocol follows the Preferred Reporting Items for Systematic Reviews and Meta-Analyses protocol statement. We will search the following databases: PubMed, Embase, Web of Science, Cochrane Library, China National Knowledge Infrastructure, Wanfang Database, Weipu Journal Database, and Chinese Biomedical Literature Database. The search time will be set from database establishment to February 2022. After literature screening, 2 reviewers will extract data from the respects of general information, methodology, and results. Risk of bias is assessed using the Cochrane Risk of Bias Tool for randomized controlled trials. We will apply RevMan 5.4 software for statistical analysis.

Results:

The results will be submitted to a peer-reviewed journal once completed.

Conclusion:

Septic patients with myocardial dysfunction may partly benefit from levosimendan than dobutamine, mainly embodied in cardiac function improvement.
Relationship between nutritional biomarkers and occlusal status in gastric cancer patients using the Eichner index
Authors: Abe Atsushi , Ito Yu , Hayashi Hiroki , Nakayama Atsushi , Furuta Hiroshi , Momokita Moeko , Hasegawa Hiroaki , Tsunoda Akari
Published: March 2022

Systemic inflammatory responses and nutritional status are useful prognostic factors in gastric cancer patients. Since oral hypofunction causes undernutrition, we cross-sectionally investigated whether nutritional biomarkers were affected by the occlusal supporting zone status.

In 114 gastric cancer patients, the gastric cancer stage, body mass index, albumin levels, total lymphocyte counts, cholesterol levels, C-reactive protein levels, and 4 nutritional biomarkers - the Glasgow prognostic score (GPS), neutrophil-lymphocyte ratio, prognostic nutrition index (PNI), and controlling nutritional status (CONUT) - were evaluated. Oral conditions were assessed by determining the number of remaining teeth. The occlusal supporting status was based on the Eichner classification. Patients were assigned into 3 groups per their occlusal status, and mean values were compared using the Kruskal-Wallis test. The mean age and body mass index were 72.2 ± 8.5 (50-89) years and 22.0 ± 3.6 (14.8-33.4), respectively. There were 42, 39, 23, and 10 patients in stages I, II, III, and IV, respectively. The mean number of remaining teeth was 18.1 ± 9.5. According to the Eichner classification, there were 45, 42, and 27 patients in groups A, B, and C, respectively. The GPS and neutrophil-lymphocyte ratio values and CONUT frequencies between groups A and C were significantly different (P = .033, P = .00097, P = .04, respectively; Mann-Whitney U test). PNI values were lower in group C with poor occlusal support zones than in group A with stable occlusal support zones.

Occlusal supporting zone reductions were undernutrition associated. Eichner Class C patients with few occlusal supporting zones had poor GPS, PNI, and CONUT values and were undernourished.
Age-specific reference values for the 5th generation cardiac troponin T assay in Chinese children
Authors: Shen Hanjun , Jiang Li , Ji Jian , Wang Cheng , Ju Qiwen , Zhao Yuqi , Wei Jia , Xu Jian
Published: March 2022

The clinical use of the cardiac troponin T (cTnT) assay was limited to the adult population in the diagnosis and prognosis of myocardial injury. However, emerging studies indicated its significant value in the assessment of pediatric cardiology, and it has been routinely measured in most hospitals. Our study investigated the normative values of cTnT in Chinese children and reported the age-specific 99th percentile cut-off for them.

A total of 1280 apparently healthy Chinese children were enrolled in our study. Serum levels of cTnT were analyzed on the Roche Elecsys Troponin T Gen 5 STAT assay. According to the Clinical and Laboratory Standards Institute C28-A3 guideline, the 99th percentile upper reference limits (URLs) with 90% confidence intervals (CIs) were calculated in different age subgroups.

The 99th percentile URL was 38 (90%CI: 37.0-51.0) ng/L for 1 to <4months old, 26 (90%CI: 25.2-28.5) ng/L for 4 to ≤ 12months old, and 12 (90%CI: 11.1-12.9) ng/L for 1 to 18 years old, respectively. For subjects aged from 1 to 18years, boys had slightly higher cTnT levels than girls (P = .003), while our assay could not measure low cTnT concentrations (≥the limit of detection) in 50% girls.

Our study provided age-specific URLs of cTnT for Chinese children, with the 5th generation cTnT assay from Roche Diagnostics. It had significant clinical implications in the interpretation and use of test results for pediatric cardiology.
Extremely premature infants with patent ductus arteriosus closure
Authors: Pandey Rajesh , Youmans Lydia , Aneji Chiamaka , Bell Cynthia , Breinholt John , Khan Amir
Published: March 2022

Our objective was to compare postprocedure hemodynamic decompensation in extremely premature infants who had their patent ductus arteriosus (PDA) closed with surgical ligation (SL) versus cardiac catheter-based closure (CCC).

This is a single-center retrospective review of extremely premature ( < 28 weeks) infants who had their PDA closed by SL or CCC.

Of the total of 69 infants, 53 underwent SL, and 16 had CCC. Infants in 2 groups were comparable at birth. However, at the time of the procedure, infants in the SL group were smaller, less mature, and had higher respiratory support. Vasopressor use, both pre- and postprocedure, was more common in the SL group. Nineteen percent of the infants in the SL group, compared to 6% in the CCC group (P = .34), required dose escalation or use of vasopressors after the PDA closure.

There was no significant difference between the 2 groups in postoperative hemodynamic decompensation. Large, multicenter, prospective study or randomized control trial will help to confirm our findings.
The effectiveness and safety of Wu tou decoction on rheumatoid arthritis
Authors: Moon Jeong-Hyun , Sung Won-Suk , Choi Seong-Kyeong , Kim Jung-Hyun , Suh Jin-woo , Kim Joo-Hee , Seo Byung-Kwan , Lee Seung-Deok , Kim Eun-Jung
Published: March 2022

Background:

Rheumatoid arthritis (RA) is one of the common inflammatory diseases with arthritis due to a malfunction of the immune system. The treatments for RA include surgery, physiotherapy, occupational therapies, and medication. The representative treatment is medication and its usage has improved through several guidelines. However, it has some limitations and occurs adverse effects. Meanwhile, traditional Chinese medicine treatments have been used for RA treatment and Wu tou decoction (WTD) is one of them. Regardless of recent studies about WTD’s efficacy on RA, there has been no systematic review on this issue. Therefore, this review will focus on the effectiveness and safety of WTD on RA.

Methods:

The search for randomized controlled trial about WTD on RA will be performed using multiple electronic databases, manual searches, and the author’s e-mail if necessary. According to predefined criteria, randomized controlled trials will be selected and summarization will be performed by the data on study participants, result measurements, interventions, adverse events, and risk of bias. Disease activity score including effective rate, swollen joint count, tender joint count, morning stiffness will be primary outcome measures while blood test about RA including erythrocyte sedimentation rate, C-reactive protein, rheumatoid factors, and adverse events will be secondary outcome measures. We will perform meta-analysis by using Review Manager software, assess the risk of bias by Cochrane Collaboration “risk of bias” tool, and determine the quality of evidence by Grades of Recommendation, Assessment, Development, and Evaluation.

Results:

This study we will investigate the clinical evidence of the effectiveness and safety of WTD on RA.

Conclusion:

For the RA patients and clinicians, our study will be informative. It can be also a great help for the researchers and policy makers who concentrates on conservative management for RA.

Trial registration number:

INPLASY; INPLASY202220099
Global status and trends in heart failure with preserved ejection fraction over the period 2009-2020
Authors: Dong Qiuju , Zhang Junwei , Han Qinghua , Zhang Hongzhen , Wang Meiling , Huang Qi , Zhao Jianping
Published: March 2022

Background:

Heart failure with preserved ejection fraction (HFpEF) comprises about 50% of the cases of heart failure (HF), but so far there is no effective treatment strategy. This study used bibliometric methods to analyze the scientific literature on HFpEF in 2009 to 2020, and evaluate the global scientific output of HFpEF research, in order to explore the research status and trends in this field.

Methods:

Documents about the HFpEF research published in 2009 to 2020 were retrieved from Science Citation Index Expanded (SCIE) in Web of Science. This study used bibliometrix R-package, VOSviewer, and CiteSpace to conduct the bibliometric analysis.

Results:

A total of 1971 documents (1508 articles and 283 reviews) were retrieved to construct the local HFpEF literature collection for analysis. The number of annual documents had increased year by year in general, from 24 to 353. Relevant documents were mainly written in English, and mostly focused on the field of “Cardiovascular System Cardiology.” USA ranked first in the relevant countries/regions with most documents, and the leading affiliation was Mayo Clin. Shah SJ was the most productive author, while Borlaug BA ranked highest among the local cited authors and G-index. Circulation was the most local cited source, while Eur J Heart Fail published the most documents and was rated as the top source in terms of G-index. “Paulus WJ, 2013, J Am Coll Cardiol” was the top local cited document within the local HFpEF literature collection, while “Owan TE, 2006, New Engl J Med” outside the local HFpEF literature collection was the most local cited reference. The keywords such as “mortality,” “dysfunction,” “diagnosis,” “outcomes,” and “diastolic dysfunction” were most frequent, while “hemodynamics,” “comorbidity,” “myocardial infarction,” “inflammation,” and “phenotype” indicated research frontiers or emerging trends. Furthermore, this study also found some deeper bibliometric relationships through bibliographic networks.

Conclusions:

Due to the multi-dimensional bibliometric analysis, this study shows a wide view of scientific productivity related to HFpEF, and provides valuable guidance for researchers interested in HFpEF, assisting them in understanding the research status, identifying potential collaborators, discovering research hotspots and frontiers, and conducting more in-depth research.
Painful subacute thyroiditis occurring after the administration of influenza vaccine and hyaluronic acid dermal filler
Authors: Bulatova Nailya R. , Zayed Ayman A. , Hijjawi Ula Qasem , Sharkas Satani G. , Bakri Faris G.
Published: March 2022

Rationale:

The occurrence of subacute thyroiditis (SAT) after vaccines or after hyaluronic acid skin fillers is very rare and might be related to genetic susceptibility. We suggest that the co-administration of both products could potentially increase the possibility of development of SAT.

Patient concerns:

A 58-year-old Caucasian healthy female initially presented with chills, myalgia, dysphagia, sore throat, dry cough, fatigue, and intermittent fever of 38.5°C orally after simultaneous injection of an influenza vaccine and a dermal filler containing hyaluronic acid. Ten days later the patient developed palpitations and neck pain radiating to the left jaw.

Diagnosis and interventions:

She was diagnosed with SAT on day 16 after her first visit and responded promptly to etoricoxib treatment.

Outcomes:

The patient progressed clinically from hyperthyroidism to euthyroid state and eventually to hypothyroidism and further testing showed she had HLA B-35 haplotype.

Lessons:

Physicians should be aware that SAT might be associated with the administration an influenza vaccine and this possible association might increase if the vaccine was co-administered with a dermal filler.
The first report on effect of fecal microbiota transplantation as a complementary treatment in a patient with steroid-refractory Cronkhite-Canada syndrome
Authors: Kim Sun Young , Shin Jongbeom , Park Jin-Seok , Cha Boram , Seo Youjeong , Park Soo-Hyun , Lee Jung Hwan , Kim Jun-Seob , Kwon Gyesook
Published: March 2022

Rationale:

Cronkhite-Canada syndrome (CCS) is a rare non-hereditary disease of unknown etiology that is characterized by the appearance of multiple polyps in the entire gastrointestinal (GI) tract, except in the esophagus, with GI and non-GI symptoms. Various factors are associated with the pathogenesis of CCS. Immune dysregulation has been discussed as one of the pathogeneses of CCS, and dysbiosis of the gut microbiota can affect the immune system. Currently, standard treatment has not been established.

Patient concerns and diagnosis:

We present the treatment with fecal microbiota transplantation (FMT) in a 67-year-old male patient with steroid-refractory CCS who could not undergo anti-tumor necrosis factor-a treatment due to suspected tuberculosis infection.

Interventions:

FMT has recently attracted attention as a method of overcoming drug resistance through immunomodulatory effects through microbiome regulation. We collected the patient's stool samples before FMT and 8weeks after FMT.

Outcomes:

We analyzed the microbiome composition of patients by sequencing the V3-V4 region of the 16s rRNA gene (Miseq). After FMT, the number of episodes of diarrhea and hypoalbuminemia were also corrected. The Chao 1 index after FMT, which was significantly higher than that of donors before FMT, changed to a similar level for donors after FMT. Fusobacterium nucleatum, Pyramidobacter piscolens, and Campylobacter concisus disappeared after FMT, suggesting the presence of an association between gut microbiota and CCS.

Lessons:

Furthermore, we provide the possibility that microbiome modulation by FMT could serve as a complementary treatment in patients with steroid-refractory CCS.
Racial Discrimination and Race-Based Biases on Orthopedic-Related Outcomes
Authors: Bond Jerenda , Julion Wrenetha A. , Reed Monique
Published: March 2022

Musculoskeletal diseases often lead to functional limitations and debility. The burden of these debilitating diseases is not balanced across race and ethnicity. The Institute of Medicine (now referred to as the National Academy of Medicine) identified racial discrimination as a substantive cause of race-based health disparities for racial and ethnic minority groups. The purpose of this integrative review is to summarize the evidence on the relationship among racial discrimination, race-based implicit biases and other types of biases (e.g., gender and appearance), and orthopaedic-related outcomes. Nine studies met inclusion criteria and were included in this review. The orthopaedic outcomes addressed across the nine studies were osteoarthritis, rheumatoid arthritis, low back pain, pain tolerance, disability, and likelihood of being recommended for a total knee arthroplasty. The results reveal that experiences of racial discrimination, race-based implicit biases, and other types of biases contribute to unsatisfactory orthopaedic-related outcomes for minority groups. Orthopaedic nurses can leverage their expertise to address these disparities in orthopaedic-related outcomes across minority groups.
The Future of Nursing
Authors: Sedlak Carol A. , Kujath Amber S. , Luther Brenda
Published: March 2022

The Future of Nursing 2020–2030: Charting a Path to Achieve Health Equity report was released in May 2021 by the National Academies of Sciences, Engineering, and Medicine. The goal is attainment of health equity in the United States using nursing capacity and expertise by designing a pathway for the nursing profession to generate a culture of health, reduce health disparities, and improve the nation's health and well-being. The focus of this article is to develop an awareness and understanding of the nine Future of Nursing recommendations for attaining health equity over the next decade with an application to orthopaedic nursing.
Predictors of Persistent Postsurgical Pain After Hysterectomy—A Prospective Cohort Study
Authors: Benlolo Samantha , Hanlon John G. , Shirreff Lindsay , Lefebvre Guylaine , Husslein Heinrich , Shore Eliane M.
Published: March 2022

(Abstracted from J Minim Invasive Gynecol 2021;28:2036–2046)

This prospective cohort study was designed to determine sociodemographic, surgical, and psychologic risk factors (including pain sensitivity) for persistent postsurgical pain (PPSP) after hysterectomy. The study was conducted at a Canadian academic medical center between 2013 and 2014.
Factors Affecting Response to Anakinra in Crystalline Arthritis Flares
Authors: Ahmed Hamdy Mohamed Abdelaziz , Sun Dongmei , Gaffo Angelo
Published: March 2022

Background

Interleukin 1 inhibition with anakinra has shown efficacy in the management of crystalline-induced arthritis (CIA) flares. Gout treatment guidelines recommend its use after contraindication or intolerance to first-line therapies. The aim of this study is to identify features associated with better response to anakinra when used to treat CIA flares.

Methods

This is a medical record review study that included inpatients with acute CIA in whom anakinra was used between the years 2014 and 2019 at one tertiary center (University of Alabama at Birmingham). The primary end point was response to anakinra treatment defined as a decrease in the reported visual analog score of at least 50% within 48 hours of initiation of treatment. Demographic, clinical, and laboratory factors were compared, and factors found significant in bivariate analysis at a p value of less than 0.15 were tested in a multivariate logistic regression analysis for independent association with the response.

Results

A total of 55 admission encounters were analyzed. The mean age was 60.1 years, 36 (66%) were men, and 31 (56%) were African Americans. Twenty-eight of 49 (57%) met the primary end point of response at 48 hours, but 52 of 55 (94.5%) ultimately responded to anakinra during hospital stay. Factors associated with response at 48 hours were race, reason for admission related to cardiac etiologies, not having failed steroids before trial of anakinra, and hospital admission within 48 hours of initiation of flare. On a multivariable logistic regression model, we could not find significant independent associations with response to anakinra.

Conclusions

Our study showed high response rates to anakinra. We could not identify factors associated with a more robust, early response. It is likely that anakinra is equally effective across a wide range of clinical scenarios.
Differences in mental health engagement and follow-up among Black and White patients after traumatic injury
Authors: Bernard Donte L. , O'Loughlin Kerry , Davidson Tatiana M. , Rothbaum Alex , Anton Margaret T. , Ridings Leigh E. , Cooley John L. , Gavrilova Yulia , Hink Ashley B. , Ruggiero Kenneth J.
Published: March 2022

BACKGROUND

Severe injury necessitating hospitalization is experienced by nearly three million US adults annually. Posttraumatic stress disorder and depression are prevalent clinical outcomes. The mechanisms by which programs equitably promote mental health recovery among trauma-exposed patients are understudied. We evaluated clinical outcomes and engagement among a cohort of Black and White patients enrolled in the Trauma Resilience and Recovery Program (TRRP), a stepped-care model to accelerate mental health recovery after traumatic injury.

METHODS

Trauma Resilience and Recovery Program is a four-step model that includes (1) bedside psychoeducation about mental health recovery following traumatic injury, (2) a text-messaging symptom tracking system, (3) a 30-day postinjury mental health screen, and (4) referrals to mental health services. Data describe 1,550 patients enrolled in TRRP within a Level I trauma center (M
age = 40.86; SD, 17.32), 611 of whom identified as Black (74.5% male) and 939 of whom identified as White (67.7% male).

RESULTS

Enrollment in TRRP was nearly universal (97.9%) regardless of race or injury mechanism. Enrollment and usage of the text-message system were statistically similar between Black (35.7%) and White patients (39.5%). Trauma Resilience and Recovery Program reengaged Black and White patients at a similar rate at the 30-day postinjury follow-up. However, Black patients were more likely to report peritraumatic distress at the bedside and clinical elevations in posttraumatic stress disorder and depression on the 30-day screen. Referrals were more likely to be accepted by Black patients relative to White patients with clinically elevated symptoms.

CONCLUSION

Enrollment and engagement were comparable among Black and White patients served by TRRP. Data provide preliminary evidence to suggest that TRRP is feasible and acceptable and engages patients in mental health follow-up equitably. However, research that includes careful measurement of social determinants of health and long-term follow-up examining initiation, completion, and benefit from treatment is needed.

LEVEL OF EVIDENCE

Therapeutic/Care Management; Level III.
Outcomes after emergency general surgery and trauma care in incarcerated individuals: An EAST multicenter study
Authors: Bryant Mary K. , Tatebe Leah C. , Siva Nandini Rajaram , Udekwu Pascal O. , Wurzelmann Mary , Crandall Marie L. , Zuniga Yohan Diaz , Tran Virginia , Santos Ariel , Krause Cassandra , Turay David , Nordham Kristen D. , Taghavi Sharven , Dreesen Elizabeth B. , Scarlet Sara , Snyder Andrew , Applewhite Megan , Patel Pooja , Schroeppel Thomas J. , Rodriquez Jennifer , Kornblith Lucy Z. , Boeck Marissa A. , Bonne Stephanie , Tufariello Ann , Maine Rebecca G.
Published: March 2022

BACKGROUND

The US incarcerates more individuals than any other country. Prisoners are the only population guaranteed health care by the US constitution, but little is known about their surgical needs. This multicenter study aimed to describe the acute care surgery (ACS) needs of incarcerated individuals.

METHODS

Twelve centers prospectively identified incarcerated patients evaluated in their emergency department by the ACS service. Centers collected diagnosis, treatment, and complications from chart review. Patients were classified as either emergency general surgery (EGS) patients or trauma patients and their characteristics and outcomes were investigated. Poisson regression accounting for clustering by center was used to calculate the relative risk (RR) of readmission, representation within 90 days, and failure to follow-up as an outpatient within 90 days for each cohort.

RESULTS

More than 12 months, ACS services evaluated 943 patients, 726 (80.3%) from jail, 156 (17.3%) from prison, and 22 (2.4%) from other facilities. Most were men (89.7%) with a median age of 35 years (interquartile range, 27–47). Trauma patients comprised 54.4% (n = 513) of the cohort. Admission rates were similar for trauma (61.5%) and EGS patients (60.2%). Head injuries and facial fractures were the most common injuries, while infections were the most common EGS diagnosis. Self-harm resulted in 102 trauma evaluations (19.9%). Self-inflicted injuries were associated with increased risk of readmission (RR, 4.3; 95% confidence interval, 3.02–6.13) and reevaluation within 90 days (RR, 4.96; 95% confidence interval, 3.07–8.01).

CONCLUSION

Incarcerated patients who present with a range of trauma and EGS conditions frequently require admission, and follow-up after hospitalization was low at the treating center. Poor follow-up coupled with high rates of assault, self-harm, mental health, and substance use disorders highlight the vulnerability of this population. Hospital and correctional facility interventions are needed to decrease self-inflicted injuries and assaults while incarcerated.

LEVEL OF EVIDENCE

Prognostic and epidemiological, Level III.
Medicare claims analysis of agents used to manage dementia-related psychosis: a treatment pattern study
Authors: Rashid Nazia , Wetmore James B. , Irfan Muna , Peng Yi , Abler Victor
Published: March 2022

Currently, no agents are approved in the USA to treat dementia-related psychosis. After failure of a nonpharmacologic approach to treatment, antipsychotics or divalproex is often prescribed. We characterized existing treatment patterns in patients with dementia-related psychosis. Medicare claims data from 2008 to 2016 were used to identify patients with dementia-related psychosis. The agents and associated dosages prescribed, time to first use, and patterns of use were evaluated for agents prescribed to treat dementia-related psychosis. In total, 49 509 patients were identified as having dementia-related psychosis. Over three-quarters (76.8%) received an antipsychotic or divalproex. The most prescribed first-line agents were quetiapine (30.5%), risperidone (19.5%), and divalproex (11.2%). More than 80% of patients received a low dose of an agent, and 65.5% switched or discontinued their first-line treatment during a mean follow-up period of 1.8 years. In the absence of US FDA-approved therapies to treat dementia-related psychosis, treatment after behavioral intervention involves frequent use of low-dose antipsychotics or divalproex. The high rate of treatment switching or discontinuation is consistent with current treatment guidelines and suggests a need for an improved, standardized pharmacological approach to treat dementia-related psychosis.
The anti-virulence activity of the non-mevalonate pathway inhibitor FR900098 towards Burkholderia cenocepacia is maintained during experimental evolution
Authors: Bové Mona , Coenye Tom
Published: March 2022

Burkholderia cenocepacia

infections are difficult to treat and there is an urgent need for alternative (combination) treatments. The use of anti-virulence therapies in combination with antibiotics is a possible strategy to increase the antimicrobial susceptibility of the pathogen and to slow down the development of resistance. In the present study we evaluated the β-lactam and colistin-potentiating activity, and anti-virulence effect of the non-mevalonate pathway inhibitor FR900098 against

B. cenocepacia

in various in vitro and in vivo models. In addition, we evaluated whether repeated exposure to FR900098 alone or when combined with ceftazidime leads to increased resistance. FR900098 potentiated the activity of colistin and several β-lactam antibiotics (aztreonam, cefepime, cefotaxime, ceftazidime, mecillinam and piperacillin) but not of imipenem and meropenem. When used alone or in combination with ceftazidime, FR900098 increased the survival of infected Galleria mellonella and Caenorhabditis elegans. Furthermore, combining ceftazidime with FR900098 resulted in a significant inhibition of the biofilm formation of

B. cenocepacia

. Repeated exposure to FR900098 in the C. elegans infection model did not lead to decreased activity, and the susceptibility of the evolved

B. cenocepacia

HI2424 lineages to ceftazidime, FR900098 and the combination of both remained unchanged. In conclusion, FR900098 reduces

B. cenocepacia

virulence and potentiates ceftazidime in an in vivo C. elegans model, and this activity is not lost during the experimental evolution experiment carried out in the present study.
Rapid increase in SARS-CoV-2 seroprevalence during the emergence of Omicron variant, Finland
Authors: Ahava MJ , Jarva H , Jääskeläinen AJ , Lappalainen M , Vapalahti O , Kurkela S
Published: March 2022

Objectives

The aim of this study was to assess changes in exposure and prevalence of SARS-CoV-2 infection during the first months of emergence of Omicron variant in the Greater Helsinki area, Finland.

Methods

A prospective seroepidemiological survey of SARS-CoV-2 was conducted on 1,600 serum specimens sent to Helsinki University Hospital Laboratory (HUSLAB) for HIV serology between 15 November 2021 and 6 March 2022 (calendar weeks 46/2021 – 9/2022). For each calendar week, 100 serum specimens were randomly selected and analysed for SARS-CoV-2 IgG antibodies against nucleocapsid (N) and spike 1 (S1) protein with Abbott SARS-CoV-2 IgG (N protein) and SARS-CoV-2 IgG II Quant (S protein) tests, respectively.

Results

The prevalence of N antibodies increased from 5.2% (weeks 46-50/2021) to 28.2% (weeks 5-9/2022) during the study period. The proportion of seronegative samples as well as anti-N negative, anti-S1 positive samples decreased correspondingly from 11.6% to 3.8%, and 84.2% to 68.2%, respectively. Anti-N positive samples that were anti-S1 negative only began to appear as of week 2/2022.

Conclusions

A rapid increase in the N antibody prevalence was observed over the study period, suggesting a high transmission rate. A substantial proportion of COVID-19 cases remained undiagnosed during the emergence of Omicron variant in the Greater Helsinki Area, Finland.
Key topics in pandemic health risk communication: A qualitative study of expert opinions and knowledge
Authors: Berg Siv Hilde , Shortt Marie Therese , Røislien Jo , Lungu Daniel Adrian , Thune Henriette , Wiig Siri
Published: March 2022

Background

Science communication can provide people with more accurate information on pandemic health risks by translating complex scientific topics into language that helps people make more informed choices on how to protect themselves and others. During pandemics, experts in medicine, science, public health, and communication are important sources of knowledge for science communication. This study uses the COVID-19 pandemic to explore these experts’ opinions and knowledge of what to communicate to the public during a pandemic. The research question is: What are the key topics to communicate to the public about health risks during a pandemic?

Method

We purposively sampled 13 experts in medicine, science, public health, and communication for individual interviews, with a range of different types of knowledge of COVID-19 risk and communication at the national, regional and hospital levels in Norway. The interview transcripts were coded and analysed inductively in a qualitative thematic analysis.

Results

The study’s findings emphasise three central topics pertaining to communication about pandemic health risk during the first year of the COVID-19 pandemic in Norway: 1) how the virus enters the human body and generates disease; 2) how to protect oneself and others from being infected; and 3) pandemic health risk for the individual and the society.

Conclusion

The key topics emerging from the expert interviews relate to concepts originating from multiple disciplinary fields, and can inform frameworks for interprofessional communication about health risks during a pandemic. The study highlights the complexity of communicating pandemic messages, due to scientific uncertainty, fear of risk amplification, and heterogeneity in public health and scientific literacy. The study contributes with insight into the complex communication processes of pandemic health risk communication.
Symptom Management When Non-Invasive Advanced Respiratory Support is Used During End-of-Life Care: A Systematic Review
Authors: Wenzel David , Bleazard Lucy , Pepper Coral , Faull Christina
Published: March 2022

Objectives

to narrate the canon of knowledge around symptom control at end of life for patients using, or having recently used, non-invasive advanced respiratory support (NARS) at end of life for respiratory failure.

Methods

A systematic review forming a narrative synthesis from a wide range of sample papers from Medline, Embase, CINAHL, Emcare, Cochrane and OpenGrey databases. A secondary search of grey literature was also performed with hand searching reference lists and author citations. The review was undertaken using the ENTREQ checklist for quality.

Results

In total 15 studies were included in the synthesis and four themes were generated: NARS as a buoy (NARS can represent hope and relief from the symptoms of respiratory failure), NARS as an anchor (NARS brings significant treatment burden), Impact on Staff (uncertainty over the balance of benefit and burden as well as complex patient care drives distress amongst staff providing care) and the Process of Withdrawal (withdrawal of therapy felt to be futile exists as discrete event in patient care but is otherwise poorly defined).

Conclusion

NARS represents a complex interplay of hope, symptom control, unnaturally prolonged death and treatment burden. The literature captures the breadth of these issues but further, detailed, research is required in almost every aspect of practice around end-of-life care and NARS – especially how to manage symptoms at the end of life.
Association between central blood pressure, arterial stiffness and low cognitive scores in South African adults
Authors: Mpondo Feziwe , Craig Ashleigh , Kolkenbeck-Ruh Andrea , Soepnel Larske , Crouch Simone , Naidoo Sanushka , Norris Shane A. , Davies Justine , Ware Lisa J.
Published: March 2022

Background

The burden of hypertension in South Africa, as well as the successive cardiovascular morbidity and mortality is increasing. Hypertension presents a risk for subsequent cognitive impairment with age. This study sought to determine the association between blood pressure, arterial stiffness, using pulse wave velocity and pulse amplification pressure, and cognitive function in younger and older adults from a 30yr old urban South African birth cohort study.

Methods

We conducted a cross-sectional study among n=93 index children (now age 29yr) and their mothers (all women). We collected peripheral and central blood pressure (BP) variables, and conducted a cognitive assessment using the Montreal Cognitive Assessment (MoCA) instrument and analysed the association of BP variables with global cognitive tests and specific domains.

Results

Forty percent of the pooled sample had low MoCA total scores, and 32% of the total sample had hypertension. No associations were found in the regression analysis between BP related variables and total MoCA scores. Also, no associations were found between peripheral and central BP variables with individual cognitive domains when stratified by age. A significant relationship was found between mean pressure and low visual perception (i.e. the ability to interpret information that is seen and give it meaning; p=0.02).

Conclusion

Central mean pressure is associated with low visual perception domain among black women. These findings add to the growing evidence which suggests that central BP variables are important to explore as exposure proxies for studying the association of BP and cognitive decline especially at mid-life.
Evaluation of the broth microdilution methodology for susceptibility testing of Mycobacterium tuberculosis in Peru
Authors: Puyen Zully M. , Santos-Lázaro David , Vigo Aiko N. , Coronel Jorge , Alarcón Miriam J. , Cotrina Vidia V. , Moore David A.J.
Published: March 2022

Peru is amongst the 30 countries with the highest burden of multidrug-resistant tuberculosis worldwide. In the fight against drug-resistant tuberculosis, the UKMYC6 microtiter plate was developed and validated by the CRyPTIC project. Our objective was to evaluate the use of the broth microdilution UKMYC6 plate for susceptibility testing of drug-resistant Mycobacterium tuberculosis (MTB) strains in Peru. 496 nationally-representative MTB strains determined drug-resistant by the routine agar proportion method (APM) were selected. MICs of 13 anti-tuberculosis drugs were determined for each strain using the microdilution UKMYC6 plates and compared with the APM result. MIC distributions for APM-susceptible and APM-resistant strains were demonstrated for rifampicin, isoniazid, kanamycin, and levofloxacin, with reasonable agreement (0.64≤k≤0.79) for rifampicin, ethambutol, ethionamide and kanamycin and the best agreement for isoniazid and levofloxacin (k>0.8). No strain presented MICs higher than the CRyPTIC Epidemiological cut-off values for the new (bedaquiline, delamanid) or repurposed (clofazimine, linezolid) drugs. The microbroth dilution method using the UKMYC6 microtiter plate allowed the complete susceptibility characterization, through the determination of MICs, of drug-resistant Mycobacterium tuberculosis strains in Peru. This methodology showed a good diagnostic performance for the drugs rifampicin, isoniazid, kanamycin and levofloxacin drugs.
SARS-CoV-2 Omicron neutralization and risk of infection among elderly after a booster dose of Pfizer vaccine
Authors: Bruel Timothée , Pinaud Laurie , Tondeur Laura , Planas Delphine , Staropoli Isabelle , Porrot Françoise , Guivel-Benhassine Florence , Attia Mikaël , Pelleau Stéphane , Woudenberg Tom , Duru Cécile , Koffi Aymar Davy , Castelain Sandrine , Fernandes-Pellerin Sandrine , Jolly Nathalie , De Facci Louise Perrin , Roux Emmanuel , Ungeheuer Marie-Noëlle , Van Der Werf Sylvie , White Michael , Schwartz Olivier , Fontanet Arnaud
Published: March 2022

Background

The protective immunity against Omicron following a BNT162b2 Pfizer booster dose among elderly is not well characterized.

Methods

Thirty-eight residents from three nursing homes were recruited for the study. Antibodies targeting the Spike protein of SARS-CoV-2 were measured with the S-Flow assay. Neutralizing activities in sera were measured as effective dilution 50% (ED50) with the S-Fuse assay using authentic isolates of Delta and Omicron.

Results

Among the 38 elderly included in the study, with median (inter-quartile range, IQR) age of 88 (81-92) years, 30 (78.9%) had been previously infected. The ED50 of neutralization were lower against Omicron than Delta, and higher among convalescent compared to naive residents. During an Omicron epidemic affecting two of the three nursing homes in December 2021-January 2022, 75% (6/8) of naive residents got infected, compared to 25% (6/24) of convalescents (P=0.03). Antibody levels to Spike and ED50 of neutralization against Omicron after the BNT162b2 booster dose were lower in those with breakthrough infection (n=12) compared to those without (n=20): median of 1256 vs 2523 BAU/mL (P=0.02) and median ED50 of 234 vs 1298 (P=0.0004), respectively.

Conclusion

This study confirmed the importance of receiving at least three antigenic exposures to the SARS-CoV-2 Spike protein for achieving satisfactory neutralizing antibody levels. In this population, protection against Omicron infection was increased in individuals who had been previously infected in addition to the three vaccine doses. Thus, a fourth antigenic exposure may be useful in the elderly population to prevent infection with Omicron, a variant known for its high escape immunity properties.
Design, Development, and Usability Evaluation of a Voice App Experience for Heart Failure Management
Authors: Barbaric Antonia , Munteau Cosmin , Ross Heather J. , Tong Kuo-Cheng , Cafazzo Joseph A.
Published: March 2022

The use of digital therapeutics (DTx) in the prevention and management of medical conditions has increased through the years with an estimated 44 million people using one as part of their treatment plan in 2021, nearly double the amount from last year. DTx are commonly accessed through smartphone apps, but offering these treatments through an alternative input can improve the accessibility of these interventions. Voice apps are an emerging technology in the digital health field, and may be an appropriate alternative platform for some patients. This research aimed to identify the acceptability and feasibility of offering a voice app as an alternative input for a chronic disease self-management program. The objective of this project was to design, develop, and evaluate a voice app of an already existing smartphone-based heart failure self-management program, Medly, to be used as a case study. A voice app version of Medly was designed and developed through a user-centered design process. We conducted a usability study and semi-structured interviews with representative end users (n=8) at the Peter Munk Cardiac Clinic in Toronto General Hospital to better understand the user experience. A Medly voice app prototype was built using a software development kit in tandem with a cloud computing platform. Three out of the eight participants were successful in completing the usability session, while the rest of the participants were not due to various errors. Almost all (7 out of the 8) participants were satisfied with the voice app and felt confident using it. Half of the participants were unsure about using the voice app in the future, though. With these findings, design changes were made to better improve the user experience. With rapid advancements in voice user interfaces, we believe this technology will play an integral role when providing access to DTx for chronic disease management.
Orphan nuclear receptors promote alternative lengthening of telomeres (ALT) through ALT-associated PML bodies
Authors: Gaela Venus Marie , Hsia Hsuan-Yu , Boudier Thomas , Chen Liuh-Yow
Published: March 2022

Alternative lengthening of telomeres (ALT) is a telomerase-independent telomere maintenance mechanism utilized by about 15% of cancers. Orphan nuclear receptors (NRs), such as COUP-TF1, COUP-TF2, EAR2, TR2, and TR4, associate with telomeres of ALT cells by binding to variant telomeric repeats. However, how these orphan NRs function in the ALT pathway remains to be characterized. Here, we have established an ALT-inducing cell model by tethering orphan NRs to telomeres in non-ALT BJ fibroblast cells. We demonstrate that recruitment of orphan NRs to telomeres is sufficient to initiate formation of ALT-associated promyelocytic leukemia nuclear bodies (APBs) and telomeric DNA synthesis at APBs. We found that the ability of orphan NRs to initiate APB formation and recombination is dependent on the orphan NR AF2 domain, the zinc-finger protein ZNF827, and PML protein. Depletion of orphan NRs in ALT cell lines reduced APB formation and telomeric DNA synthesis, confirming the role of orphan NRs in ALT cells. Furthermore, we found that ATRX/DAXX depletion, together with the telomeric localization of orphan NRs, induces APB formation, telomere clustering, and telomeric DNA synthesis more dramatically in non-ALT cells. Accordingly, we propose that these events in ALT, orphan NR recruitment to telomeres and ATRX/DAXX loss, operate in concert to activate the ALT pathway.