bluuebunny/crossref_metadata_2025 huggingface dataset:
Knowledge, Confidence, and Perception Toward Therapeutic Drug Monitoring Among Physicians and Pharmacists in Kuwait
Authors: Albassam Abdullah , Alghanem Sarah S. , Alawadhi Farah , Alsulaimani Zainab
Published: February 2022

Background:

Therapeutic drug monitoring (TDM) helps ensure an efficient and safe therapeutic outcome. This study assessed physicians' and pharmacists' knowledge, confidence, and perception regarding clinical pharmacokinetics and TDM.

Methods:

A cross-sectional survey that used a self-administered questionnaire was used. A stratified random sample of 322 physicians and pharmacists across 3 Kuwait public hospitals was surveyed. Descriptive and comparative statistical analyses were performed during data analysis. A multivariate logistic regression model was used to identify factors associated with low levels of knowledge and confidence and negative perceptions among the subjects.

Results:

The response rate was 88%. Overall, the respondents' mean total knowledge score percentage was low (50.3%), with no significant difference between the physicians' and pharmacists' scores (P > 0.5); 60.4% of the participants (95% confidence interval: 54.9–65.6) felt confident when using TDM in their practice. Most participants expressed positive perceptions (90.1%; 95% confidence interval: 86.3–92.9) toward TDM. There was high agreement internally that pharmacists require some knowledge of TDM, should be asked by physicians in general for recommendations on the appropriate use of TDM, and should be able to provide relevant information regarding the appropriate use of TDM.

Conclusions:

Physicians and pharmacists in this study had high confidence in—and the positive perceptions of—TDM and its clinical implications. The present study's findings indicate an urgent need for professional education and training in clinical pharmacokinetics and TDM and its clinical implications through continuous professional development programs and its integration within the curricula of medical and pharmacy schools.
Patterns of mental health symptoms among women living with HIV ages 45-60 in England: associations with demographic and clinical factors
Authors: Haag Katharina , Tariq Shema , Dhairyawan Rageshri , Sabin Caroline , Okhai Hajra , Gilson Richard , Burns Fiona , Sherr Lorraine
Published: February 2022

Objective:

We aimed to describe the prevalence of various mental health symptoms according to menopausal status (pre, peri, post) among women living with HIV ages 45-60 in England, and to identify groups of women with similar general and menopause-related mental health symptoms. We then investigated demographic predictors of group-membership and group differences in HIV-related care outcomes (antiretroviral therapy adherence, HIV clinic attendance, CD4-count, and last HIV viral load).

Methods:

An analysis of cross-sectional data from the Positive Transitions through Menopause study, an observational study of the health and well-being impacts of menopause on 869 women with HIV aged 45-60 years. Self-reported data on eight mental health indicators were collected from women in pre-, peri- and post-menopausal state using validated measures. Groups (termed “classes”) of women with similar mental health symptoms were derived via latent class analysis. Class membership was linked to demographic factors using nominal logistic regression, and to clinical outcomes using Wald tests.

Results:

We identified five classes: 1) few mental health symptoms (n = 501, 57.8%); 2) high current anxiety/depression (n = 120, 13.8%); 3) history of depression, with elevated current substance use (n = 40, 4.6%); 4) history of depression with current psychological menopause symptoms (n = 81, 9.3%); and 5) high previous and concurrent mental health problems (n = 125, 14.4%). University attendance, ethnicity, and longer time since HIV diagnosis predicted class membership. Antiretroviral therapy adherence was lower in classes 3 (11%), 4 (19%) and 5 (24%) compared to class 1 (4%; all P<0.001). Members of class 5 were more likely to have missed ≥1 HIV clinic appointment in the past year than those in class 1 (34% vs 17%, P = 0.005).

Conclusions:

Women with a history of depression, current anxiety/depression, and current menopause-related mental health symptoms were more likely to have poorer clinical outcomes. Although we cannot comment on causality, our findings highlight the importance of assessing and managing menopausal symptoms and mental health to improve well-being and engagement in HIV care.
Higher SBP in female patients with mitochondrial disease
Authors: Viering Daan H.H.M. , van Borselen Marjolein D. , Deinum Jaap , Bindels Rene J.M. , de Baaij Jeroen H.F. , Janssen Mirian C.H.
Published: February 2022

Background:

Previous research suggests that hypertension is more prevalent among patients with mitochondrial diseases. Blood pressure (BP) is linearly related to increased cardiovascular risk, and this relationship is strongest for SBP; nevertheless, studies on SBP and DBP in mitochondrial diseases have not yet been performed.

Method:

In a retrospective case–control study design, BP in mitochondrial disease patients was compared with BP in a population cohort. Secondly, using multiple linear regression, we examined blood pressure differences in various genetic mitochondrial diseases. Lastly, we explored additional predictors of BP in a subgroup with the m.3243A > G variant.

Results:

Two hundred and eighty-six genetically confirmed mitochondrial disease patients were included. One hundred and eighty of these patients carried the m.3243A>G mitochondrial DNA variant. SBP was 9 mmHg higher in female mitochondrial disease patients than in the general female population (95% CI: 4.4–13.3 mmHg, P 
< 0.001), whereas male patients had similar BP compared with controls. BP was not significantly different in patients with m.8344A>G and m.8363G>A, a mtDNA deletion or a nuclear mutation compared with m.3243A>G patients. Higher SBP was a predictor for left ventricular hypertrophy in the m.3243A>G subgroup (P 
= 0.04).

Conclusion:

Novel aspects of the role of mitochondrial dysfunction in blood pressure regulation are exposed in this study. Compared with the general population, female mitochondrial disease patients have a higher SBP. Left ventricular hypertrophy is more prevalent in patients with higher SBP. Clinicians should be aware of this to prevent hypertensive complications in mitochondrial disease patients.
Keeping It Real: Infection Prevention and Control Problems and Solutions in Low- and Middle-income Countries
Authors: Dramowski Angela , Bekker Adrie , Anugulruengkitt Suvaporn , Bayani One , Martins Gonçalves Fernanda , Naizgi Mulugeta , Magnino Aline , Puthanakit Thanyawee , Salle Fernanda , da Silva André Ricardo Araujo , Molyneux Elizabeth , Strysko Jonathan , Vieira Cristina , Coffin Susan
Published: February 2022

Infection prevention challenges are ubiquitous in healthcare, but some are unique to or more prevalent in low-and middle-income country settings. Despite limited resources, innovative and committed paediatric healthcare providers and infection preventionists have found creative solutions to address the very real and pressing risks their patients face every day. We gathered examples of infection prevention and control challenges faced by clinicians in resource-limited healthcare facilities, and the real-world infection prevention and control solutions they implemented, with the goal of learning broader lessons applicable to low-and middle-income countrie.
Long-term clinical impact of low-density lipoprotein cholesterol target attainment according to lesion complexity after percutaneous coronary intervention
Authors: Kim Byung-Jun , Lee Jung-Hee , Park Jong-Il , Nam Jong-Ho , Lee Chan-Hee , Son Jang-Won , Kim Ung , Shin Dong-Gu , Park Jong-Seon
Published: February 2022

Objective

Long-term clinical outcomes of low-density lipoprotein cholesterol (LDL-C) target attainment according to coronary lesion complexity are limited. We investigated the clinical outcomes of LDL-C target attainment after percutaneous coronary intervention (PCI) according to coronary lesion complexity.

Methods

A total of 1285 patients who underwent PCI was categorized by LDL-C target attainment at 1 year and lesion complexity: LDL-C levels less than or equal to 70 mg/dl (n = 179) and greater than 70 mg/dl (n = 308) in complex PCI; LDL-C levels less than or equal to 70 mg/dl (n = 315) and greater than 70 mg/dl (n = 483) in noncomplex PCI. The primary endpoint was major adverse cardiovascular events (MACEs) and defined as cardiac death, nonfatal myocardial infarction, and target vessel revascularization.

Results

At 8-year follow-up, comparison of patients with 1-year LDL-C levels less than or equal to 70 mg/dl and 1-year LDL-C levels greater than 70 mg/dl showed similar MACE incidence in the noncomplex PCI group (8.3% vs. 11.6%; P = 0.074) and significantly lower MACE incidence in the complex PCI group (11.7% vs. 19.2%; P = 0.023). After IPTW adjustment, 1-year LDL-C levels less than or equal to 70 mg/dl was associated with reduced MACE rate in both complex PCI and noncomplex PCI groups.

Conclusion

Although the attainment of LDL-C levels less than or equal to 70 mg/dl was associated with reduced MACE rate in both complex PCI and noncomplex PCI groups, long-term clinical benefits were prominent in the complex PCI group.
Radiomics: a quantitative imaging biomarker in precision oncology
Authors: Jha Ashish Kumar , Mithun Sneha , Purandare Nilendu C. , Kumar Rakesh , Rangarajan Venkatesh , Wee Leonard , Dekker Andre
Published: February 2022

Cancer treatment is heading towards precision medicine driven by genetic and biochemical markers. Various genetic and biochemical markers are utilized to render personalized treatment in cancer. In the last decade, noninvasive imaging biomarkers have also been developed to assist personalized decision support systems in oncology. The imaging biomarkers i.e., radiomics is being researched to develop specific digital phenotype of tumor in cancer. Radiomics is a process to extract high throughput data from medical images by using advanced mathematical and statistical algorithms. The radiomics process involves various steps i.e., image generation, segmentation of region of interest (e.g. a tumor), image preprocessing, radiomic feature extraction, feature analysis and selection and finally prediction model development. Radiomics process explores the heterogeneity, irregularity and size parameters of the tumor to calculate thousands of advanced features. Our study investigates the role of radiomics in precision oncology. Radiomics research has witnessed a rapid growth in the last decade with several studies published that show the potential of radiomics in diagnosis and treatment outcome prediction in oncology. Several radiomics based prediction models have been developed and reported in the literature to predict various prediction endpoints i.e., overall survival, progression-free survival and recurrence in various cancer i.e., brain tumor, head and neck cancer, lung cancer and several other cancer types. Radiomics based digital phenotypes have shown promising results in diagnosis and treatment outcome prediction in oncology. In the coming years, radiomics is going to play a significant role in precision oncology.
Coronary Endothelial Dysfunction in People Living With HIV Is Related to Body Fat Distribution
Authors: Goerlich Erin , Schär Michael , Bagchi Shashwatee , Soleimani-Fard Alborz , Brown Todd T. , Sarkar Sudipa , Bonanno Gabriele , Streeb Valerie , Gerstenblith Gary , Barditch-Crovo Patricia , Weiss Robert G. , Hays Allison G.
Published: February 2022

Background:

People living with HIV (PLWH) on antiretroviral therapy (ART) are at increased risk of atherosclerotic disease. Abnormal adipose distribution is common in PLWH and may contribute to atherosclerosis. Because coronary artery endothelial function (CEF) is impaired in early atherosclerosis, predicts future cardiovascular events, and is reduced in PLWH, we investigated associations between body fat distribution and CEF in PLWH.

Setting:

Prospective cohort study.

Methods:

PLWH on stable ART underwent MRI to quantify CEF, measured as change in coronary cross-sectional area from rest to that during isometric handgrip exercise, an endothelial-dependent stressor. Abdominal visceral and subcutaneous fat area (axial L4 level) and liver fat fraction were quantified using MRI. Linear regression was used to determine associations between CEF and independent variables.

Results:

Among 84 PLWH (52 ± 11 years; 33% women), mean cross-sectional area change was 0.74 ± 11.7%, indicating impaired CEF. On univariable regression analysis, CEF was inversely related to waist circumference (R = −0.31, P = 0.014), hip circumference (R = −0.27, P = 0.037), and subcutaneous fat area (R = −0.25, P = 0.031). We did not observe significant relationships between CEF and liver fat fraction, waist/hip ratio, or visceral fat area. On multivariable regression adjusted for age, sex, and race, CEF was associated with waist circumference, hip circumference, subcutaneous fat, and liver fat fraction.

Conclusion:

Waist and hip circumference and subcutaneous fat area are associated with impaired CEF, an established metric of abnormal vascular health in PLWH on stable ART, and may contribute to the increased rate of heart disease in this population.
Technical Variations in the Management of the Medial Crural Reduction According to the Settlement of the Angulation Deformities Over Hypertrophic Lower Lateral Cartilages
Authors: Çerçi Özkan Aret , Kozanoğlu Erol
Published: February 2022

Background:

Medial crural (MC) overlay is reliable method used in tip deprojection. Most cases with lower lateral cartilage (LLC) hypertrophy present by variations of MC and dome shapes needing specific technical maneuvers.

Methods:

Thirteen hundred fourteen primary rhinoplasties were performed between 2018 and 2021. Patients with LLC hypertrophy who underwent MC deprojection were analyzed. Three variations in LLC hypertrophy were recognized. In type I, tip-defining points (TDP) were localized at the median plane with no angulation deformities at the LLC, which was managed by horizontal cuts of the lobular segments 4 to 6 mm below the domes. The cut fragments overlapped for 2 to 5 mm. In type II, TDP was lateralized due to widened divergence angles at the columellalobular junctions, which were managed by horizontal cuts over columellalobular junctions. The cut fragments overlapped 4 to 6 mm. In type III, TDP was localized at the median plane, there were dense angulations at the medial genu, which was managed with symmetrical removal of 4 to 5 mm cartilage from lobular segments. The domes were sutured over the medial segments.

Results:

Nineteen patients with LLC hypertrophy were included in the study among 314 patients. Twelve patients were female and 7 patients were male. The mean age was 32 years (25–42). Type I, II, and III LLC hypertrophies were detected in 10, 3, and 6 patients, respectively. A harmonious relationship between dorsum and tip and satisfactory tip stability was reached in all patients.

Conclusions:

By classification of variations of MC and domal shapes, LLC hypertrophies may be managed with proper technical maneuvers specific to each type.
Enhanced Recovery After Surgery for Pediatric Cleft Repair: A Systematic Review and Meta-Analysis
Authors: Shin Max , Wagner Connor , Prasad Aman , Barrette Louis-Xavier , Chorath Kevin , Moreira Alvaro , Rajasekaran Karthik
Published: February 2022

Objective:

Perform a systematic review assessing the efficacy of enhanced recovery after surgery (ERAS) protocols for cleft palate repair. Primary outcomes included hospital length of stay, readmission rates, and postoperative narcotic use. Secondary outcomes included complications, time to initial postoperative oral intake, and pain scores.

Data Sources:

Cohort and randomized studies of ERAS protocols pertaining to cleft palate repair were identified by systematic review of Medline, Scopus, Embase, and grey literature.

Review Methods:

Data extracted included patient demographics, clinical care protocols, complication rates, postoperative narcotic use, time to initial postoperative oral intake, hospital length of stay, family satisfaction, and 30-day readmission. Meta-analysis was used to compare outcomes between patients enrolled in ERAS protocols versus those in conventional care pathways.

Results:

Eight hundred sixty-five articles were screened, and 5 studies met full inclusion criteria. A total of 425 patients were included. Patients in ERAS protocols saw a mean reduction of – 23.96 hours in length of stay compared to controls (95% confidence interval [CI]: – 26.4, – 20.6). Patients in ERAS protocols also had decreased total morphine consumption (mean difference [MD]: – 3.88 mg; CI: – 4.31, – 3.45), and decreased time to first initial feed compared to controls (MD: – 3.88 hours; CI: – 4.3, – 3.5). There was no difference in readmission rates or complication rates between ERAS and control groups.

Conclusions:

ERAS protocols have seen limited use in pediatric patients. The present study sought to assess the impact of ERAS protocols following primary palatoplasty. Our results indicate decreased hospital length of stay, postoperative opioid consumption, and time to feeding, without increasing readmission rates or complication rates.
Morphometric Analysis of the Cranial Fossae in Scaphocephalic Patients: An Anatomical Basis
Authors: Bisetty Vensuya , Lazarus Lelika , Harrichandparsad Rohen , Madaree Anil
Published: February 2022

Scaphocephaly is the morphological consequence of premature sagittal suture fusion. Morphologic and morphometric studies on the cranial vault in scaphocephaly flourish in the literature. However, few studies are available on the cranial base in a scaphocephalic population, let alone the morphometry of its fossae. Therefore, this study aimed to analyze and compare the morphometry of the anterior, middle, and posterior cranial fossae (ACF, MCF, and PCF) in patients with scaphocephaly.

The length and width of the ACF, MCF, and PCF were measured using fixed anatomical landmarks on the two-dimensional computed tomography scans of 24 consecutive patients diagnosed with isolated sagittal synostosis between 2014 and 2020, and 14 controls.

A comparison of the results between patients with scaphocephaly and the controls showed that the ACF and PCF lengths increased significantly (P = 0.041 and P = 0.018) in patients with scaphocephaly. No differences in the MCF lengths were observed (P = 0.278; 0.774). When compared by the degree of severity, the ACF and PCF lengths were significantly increased ( analysis of variance [ANOVAI, P = 0.033; post-hoc, P = 0.013 and ANOVA, P = 0.015; post-hoc, P = 0.036) in scaphocephalic patients within the severe group as opposed to the control group.

The morphometric data obtained indicate a preponderance of deformity in the ACF and PCF with elongation along the anteroposterior plane (lengths) in scaphocephalic patients. Minimal changes were observed in the transverse plane (widths) in scaphocephaly versus controls. This data could aid craniofacial surgeons in understanding the affectation of the cranial fossae and influencing the decision on the most suitable method of corrective modality.
Tracing genetic connections of ancient Hungarians to the 6-14thcentury populations of the Volga-Ural region
Authors: Szeifert Bea , Gerber Dániel , Csáky Veronika , Langó Péter , Stashenkov Dmitrii A. , Khokhlov Aleksandr A. , Sitdikov Ayrat G. , Gazimzyanov Ilgizar R. , Volkova Elizaveta V. , Matveeva Natalia P. , Zelenkov Alexander S. , Poshekhonova Olga E. , Sleptsova Anastasiia V. , Karacharov Konstantin G. , Ilyushina Viktoria V. , Konikov Boris A. , Sungatov Flarit A. , Kolonskikh Alexander G. , Botalov Sergei G. , Grudochko Ivan V. , Komar Oleksii , Egyed Balázs , Mende Balázs G. , Türk Attila , Szécsényi-Nagy Anna
Published: February 2022

Most of the early Hungarian tribes originated from the Volga-Kama and South-Ural regions, where they were composed of a mixed population based on historical, philological, and archaeological data. We present here the uniparental genetic makeup of the medieval era of these regions that served as a melting pot for ethnic groups with different linguistic and historical backgrounds. Representing diverse cultural contexts, the new genetic data originates from ancient proto-Ob-Ugric people from Western Siberia (6th-13thcentury), the pre-Conquest period, and subsisting Hungarians from the Volga-Ural region (6th-14thcentury) and their neighbours. By examining the eastern archaeology traits of Hungarian prehistory, we also study their genetic composition and origin in an interdisciplinary framework.

We analysed 110 deep-sequenced mitogenomes and 42 Y-chromosome haplotypes from 18 archaeological sites in Russia. The results support the studied groups’ genetic relationships regardless of geographical distances, suggesting large-scale mobility. We detected long-lasting genetic connections between the sites representing the Kushnarenkovo and Chiyalik cultures and the Carpathian Basin Hungarians and confirmed the Uralic transmission of several East-Eurasian uniparental lineages in their genepool. Based on phylogenetics, we demonstrate and model the connections and splits of the studied Volga-Ural and conqueror groups.

Early Hungarians and their alliances conquered the Carpathian Basin around 890 AD. Re-analysis of the Hungarian conquerors’ maternal genepool reveals numerous surviving maternal relationships in both sexes; therefore, we conclude that men and women came to the Carpathian Basin together, and although they were subsequently genetically fused into the local population, certain eastern lineages survived for centuries.
Specific Peptides Predict Protein Classification
Authors: Horn David , Weingart Uri
Published: February 2022

The methodology of Specific Peptides (SP) has been introduced within the context of enzymes. It is based on an unsupervised machine leaning (ML) tool for motif extraction, followed by supervised annotation of the motifs. In the case of enzymes, the classifier is the Enzyme Classification (EC) number. Here we demonstrate that this method reaches precision of 96.5% and recall of 89.1% on presently available protein sequences. We also apply this method to two other protein families, GPCR and ZF, find their corresponding SPs, and provide the code for searching any protein sequence for its classification under any such family.
Lipid network and moiety analysis for revealing enzymatic dysregulation and mechanistic alterations from lipidomics data
Authors: Rose Tim D. , Köhler Nikolai , Falk Lisa , Klischat Lucie , Lazareva Olga E. , Pauling Josch K.
Published: February 2022

Lipidomics is of growing importance for clinical and biomedical research due to many associations between lipid metabolism and diseases. The discovery of these associations is facilitated by improved lipid identification and quantification. Sophisticated computational methods are advantageous for interpreting such large-scale data for understanding metabolic processes and their underlying (patho)mechanisms. To generate hypothesis about these mechanisms, the combination of metabolic networks and graph algorithms is a powerful option to pinpoint molecular disease drivers and their interactions. Here we present LINEX2(Lipid Network Explorer), a lipid network analysis framework that fuels biological interpretation of alterations in lipid compositions. By integrating lipid-metabolic reactions from public databases we generate dataset-specific lipid interaction networks. To aid interpretation of these networks we present an enrichment graph algorithm that infers changes in enzymatic activity in the context of their multispecificity from lipidomics data. Our inference method successfully recovered the MBOAT7 enzyme from knock-out data. Furthermore, we mechanistically interpret lipidomic alterations of adipocytes in obesity by leveraging network enrichment and lipid moieties. We address the general lack of lipidomics data mining options to elucidate potential disease mechanisms and make lipidomics more clinically relevant.

Graphical Abstract

LINEX2(Lipid Network Explorer) is a framework to visualize and analyze quantitative lipidomics data. The included algorithms offer new perspectives on the lipidome and can propose potential mechanisms of dysregulation.

Using the Reactome and Rhea databases, a comprehensive set of lipid class reactions is included and utilized to map the lipidome on custom data-specific networks.

With a novel network enrichment method, enzymatic dysregulation can be recovered from lipidomics data.

We validate its usability on data with a central lipid enzymatic deficiency.

LINEX2is the first tool capable of such analysis and includes complimentary analysis options for structural lipid analysis. It is freely available as a web service (https://exbio.wzw.tum.de/linex2).
A Suite of TMPRSS2 Assays for Screening Drug Repurposing Candidates as Potential Treatments of COVID-19
Authors: Shrimp Jonathan H. , Janiszewski John , Chen Catherine Z. , Xu Miao , Wilson Kelli M. , Kales Stephen C. , Sanderson Philip E. , Shinn Paul , Itkin Zina , Guo Hui , Shen Min , Klumpp-Thomas Carleen , Michael Samuel G. , Zheng Wei , Simeonov Anton , Hall Matthew D.
Published: February 2022

SARS-CoV-2 is the causative viral pathogen driving the COVID-19 pandemic that prompted an immediate global response to the development of vaccines and antiviral therapeutics. For antiviral therapeutics, drug repurposing allowed for rapid movement of existing clinical candidates and therapies into human clinical trials to be tested as COVID-19 therapies. One effective antiviral treatment strategy used early in symptom onset is to prevent viral entry. SARS-CoV-2 enters ACE2-expressing cells when the receptor-binding domain of the spike protein on the surface of SARS-CoV-2 binds to ACE2 followed by cleavage at two cut sites on the spike protein. TMPRSS2 has a protease domain capable of cleaving the two cut sites; therefore, a molecule capable of inhibiting the protease activity of TMPRSS2 could be a valuable antiviral therapy. Initially, we used a fluorogenic high-throughput screening assay for the biochemical screening of 6030 compounds in NCATS annotated libraries. Then, we developed an orthogonal biochemical assay that uses mass spectrometry detection of product formation to ensure that hits from the primary screen are not assay artifacts from the fluorescent detection of product formation. Finally, we assessed the hits from the biochemical screening in a cell-based SARS-CoV-2 pseudotyped particle entry assay. Of the six molecules advanced for further studies, two are approved drugs in Japan (camostat and nafamostat), two have entered clinical trials (PCI-27483 and otamixaban), while the other two molecules are peptidomimetic inhibitors of TMPRSS2 taken from the literature that have not advanced into clinical trials (compounds 92 and 114). This work demonstrates a suite of assays for the discovery and development of new inhibitors of TMPRSS2.
SARS-CoV-2 variant of concern type and biological sex affect efficacy of molnupiravir in dwarf hamster model of severe COVID-19
Authors: Lieber Carolin M. , Cox Robert M , Sourimant Julien , Wolf Josef D. , Juergens Kate , Phung Quynh , Saindane Manohar T , Natchus Michael G , Painter George R , Sakamoto Kaori , Greninger Alexander L. , Plemper Richard K
Published: February 2022

Summary Paragraph

SARS-CoV-2 variants of concern (VOC) have triggered distinct infection waves in the coronavirus disease 2019 (COVID-19) pandemic, culminating in currently all-time high incidence rates of VOC omicron. Orally available direct-acting antivirals such as molnupiravir promise to improve disease management and limit SARS-CoV-2 spread. However, molnupiravir efficacy against VOC delta was questioned based on clinical trial results and its potency against omicron is unknown. This study evaluates molnupiravir against a panel of relevant VOC in three efficacy models: primary human airway epithelium organoids, the ferret model of upper respiratory disease, and a lethal Roborovski dwarf hamster efficacy model of severe COVID-19-like acute lung injury. All VOC were equally efficiently inhibited by molnupiravir in cultured cells and organoids. Treatment consistently reduced upper respiratory VOC shedding in ferrets and prevented viral transmission. Pathogenicity in the dwarf hamsters was VOC-dependent and highest for gamma, omicron, and delta with fulminant lung histopathology. Oral molnupiravir started 12 hours after infection resulted in complete survival of treated dwarf hamsters independent of challenge VOC. However, reduction in lung virus differed VOC-dependently, ranging from one (delta) to four (gamma) orders of magnitude compared to vehicle-treated animals. Dwarf hamsters infected with VOC omicron showed significant individual variation in response to treatment. Virus load reduction was significant in treated males, but not females. The dwarf hamster model recapitulates mixed efficacy of molnupiravir seen in human trials and alerts that therapeutic benefit of approved antivirals must be continuously reassessed in vivo as new VOC emerge.
Detection of SARS-CoV-2 Omicron variant (B.1.1.529) infection of white-tailed deer
Authors: Vandegrift Kurt J. , Yon Michele , Surendran-Nair Meera , Gontu Abhinay , Amirthalingam Saranya , Nissly Ruth H. , Levine Nicole , Stuber Tod , DeNicola Anthony J. , Boulanger Jason R. , Kotschwar Nathan , Aucoin Sarah Grimké , Simon Richard , Toal Katrina , Olsen Randall J. , Davis James J. , Bold Dashzeveg , Gaudreault Natasha N. , Richt Juergen A. , Musser James M. , Hudson Peter J. , Kapur Vivek , Kuchipudi Suresh V.
Published: February 2022

White-tailed deer (Odocoileus virginianus) are highly susceptible to infection by SARS-CoV-2, with multiple reports of widespread spillover of virus from humans to free-living deer. While the recently emerged SARS-CoV-2 B.1.1.529 Omicron variant of concern (VoC) has been shown to be notably more transmissible amongst humans, its ability to cause infection and spillover to non-human animals remains a challenge of concern. We found that 19 of the 131 (14.5%; 95% CI: 0.10–0.22) white-tailed deer opportunistically sampled on Staten Island, New York, between December 12, 2021, and January 31, 2022, were positive for SARS-CoV-2 specific serum antibodies using a surrogate virus neutralization assay, indicating prior exposure. The results also revealed strong evidence of age-dependence in antibody prevalence. A significantly (χ2, p < 0.001) greater proportion of yearling deer possessed neutralizing antibodies as compared with fawns (OR=12.7; 95% CI 4–37.5). Importantly, SARS-CoV-2 nucleic acid was detected in nasal swabs from seven of 68 (10.29%; 95% CI: 0.0–0.20) of the sampled deer, and whole-genome sequencing identified the SARS-CoV-2 Omicron VoC (B.1.1.529) is circulating amongst the white-tailed deer on Staten Island. Phylogenetic analyses revealed the deer Omicron sequences clustered closely with other, recently reported Omicron sequences recovered from infected humans in New York City and elsewhere, consistent with human to deer spillover. Interestingly, one individual deer was positive for viral RNA and had a high level of neutralizing antibodies, suggesting either rapid serological conversion during an ongoing infection or a “breakthrough” infection in a previously exposed animal. Together, our findings show that the SARS-CoV-2 B.1.1.529 Omicron VoC can infect white-tailed deer and highlights an urgent need for comprehensive surveillance of susceptible animal species to identify ecological transmission networks and better assess the potential risks of spillback to humans.

Key Findings

These studies provide strong evidence of infection of free-living white-tailed deer with the SARS-CoV-2 B.1.1.529 Omicron variant of concern on Staten Island, New York, and highlight an urgent need for investigations on human-to-animal-to-human spillovers/spillbacks as well as on better defining the expanding host-range of SARS-CoV-2 in non-human animals and the environment.
Characteristics and Preparedness for COVID-19 Outbreaks of Australian Residential Aged Care Facilities: a Cross-sectional Survey
Authors: Gilbert Gwendolyn L , Smith Jenna , Cvejic Erin , Lilly Alan , McCaffery Kirsten
Published: February 2022

Objective

To provide an overview of Australian residential aged care facilities’ (RACFs’) COVID-19 outbreak preparedness and responses, 12 months after the pandemic began in early 2020.

Methods

A cross-sectional survey of RACF managers was conducted as part of an overview of COVID-19 experience during 2020. Survey questions were based on findings of previous outbreak reviews.

Results

Comparison with available data from the Australian Institute for Health and Welfare suggested that survey respondents (n=331) were a representative sample. Almost all RACFs had outbreak management plans, including provision for a surge workforce. However, anticipated staff replacements fell short of those often required during outbreaks. Staff of most (83%) RACFs had completed online infection control training, and a smaller proportion (73%) face-to-face training, by the time of the survey. Exploratory analyses to identify RACF characteristics associated with increased outbreak risk found a strong association with location in Victoria (adjusted risk ratio [aRR] 12.8) where most community transmission occurred during 2020. The only other association was an increased risk in facilities where all staff had not completed face-to-face infection control training (aRR 2.1). Respondents ranked leadership and management; planning and preparation; and infection control as the top three of seven critical lines of defence against COVID-19.

Conclusion

Survey results suggest that, in early 2021, most Australian RACFs were better prepared for the ongoing risk of COVID-19 than in 2020. Continued implementation of the Aged Care Royal Commission’s recommendations is needed to ensure the aged care sector is prepared for future infectious disease emergencies.
Estimating the risk reduction of isolation on COVID-19 non-household transmission and severe/critical illness in non-immune individuals: September to November 2021
Authors: Prosser Aaron , Helfer Bartosz , Streiner David L.
Published: February 2022

In the fall 2021, immunity mandates/passports for COVID-19 started to be discussed and implemented globally. In addition to increasing vaccination levels, these interventions isolate non-immune individuals from various settings to reduce non-household transmission and severe/critical illness. This is based on the hypothesis that the non-immune are at high absolute risk of these outcomes. However, these absolute risks were not quantified in the literature such that the absolute risk reductions of isolation on these outcomes remain unknown. This study estimated these absolute risks from September to November 2021 prior to the emergence of Omicron (B.1.1.529) using known data on the risk of infection, transmission in non-household settings, and age-stratified severe/critical illness in non-immune individuals for the Delta (B.1.617.2) variant, focusing on the European Union, United Kingdom, United States, Canada, Australia, and Israel. This allowed us to quantify the absolute risk reductions of isolation on (1) non-household transmission from the non-immune and (2) severe/critical illness amongst the non-immune in these regions during this period. We observed that on any given day the absolute risk reductions of isolation were typically small for transmission in most types of non-household settings and severe/critical illness in most age-groups, especially those aged <40. During a wave or sustained higher infection risks, the risk reductions were modest only for transmission in intimate social gatherings and severe/critical illness in adults aged ≥50-60. The limitations of this study and the implications for the expected benefits of isolating non-immune individuals on reducing these outcomes are discussed.
Changes in the number of public health nurses employed in local governments in Japan during the Covid-19 pandemic: A cross-sectional study
Authors: Taira Kazuya , Hosokawa Rikuya , Shiomi Misa
Published: February 2022

Objectives

This study aims to clarify the recruitment of public health nurses in local governments in Japan during the Covid-19 pandemic.

Study design

A cross-sectional study.

Methods

A cross-sectional study of 150 local governments that have public health centers in Japan was conducted. The survey period was November to December 2021. The survey items were the number of full-time and part-time public health nurses (PHNs), the number of PHNs who resigned or retired from the job, and the number of PHN recruitment examinations for each year from 2017 to 2021. For all variables, the mean, standard deviation, maximum, and minimum values for each type of municipality and year were calculated, and a one-way analysis of variance was performed.

Results

The recovery rate was 54.0% (81/150). Although a statistically significant difference was not recorded in the change in employment status of PHNs from 2019 to 2020, during the year that COVID-19 infection began in Japan, the number of full-time PHNs increased by only 2.6 at the maximum, while the number of part-time PHNs was 5.2±8.3 to 10.8±9.6 (p = 0.61) for prefectures, from 13.6±13.1 to 21.5±34.8 (p = 0.23) for city, and from 16.8±26.8 to 52.3±132.5 (p = 0.70) for ward.

Conclusions

This study reveals that support for the increased workload due to COVID-19 is heavily dependent on part-time PHNs. Drastic change to the ideal way of the original countermeasure to Covid-19 in Japan or the supply of stronger human support to the public health center might be desired.
COVID-19 vaccines uptake: Public knowledge, awareness, perception and acceptance among adult Africans
Authors: Ahiakpa John K. , Cosmas Nanma T. , Anyiam Felix E. , Enalume Kingsley O. , Lawan Ibrahim , Gabriel Ijuptil B. , Oforka Chinonyelum L. , Dahir Hamze G. , Fausat Salisu T. , Nwobodo Maureen A. , Massawe Getrude P. , Obagha Adachukwu S. , Okeh Debra U. , Karikari Benjamin , Aderonke Samuel T. , Awoyemi Olushola M. , Aneyo Idowu A. , Doherty Funmilayo V.
Published: February 2022

Introduction

The willingness of Africa’s population to take the COVID-19 vaccines is critical to the efficiency of national immunisation programmes. This study surveys the views of adult African inhabitants toward vaccination and the possibility of participating or not participating in governments’ efforts to get citizens vaccinated.

Method

A cross-sectional online survey of adult Africans was undertaken from December 2020 to March 2021. Responses were anonymised. The Pearson Chi-square test was performed to determine whether or not there were any variations in knowledge, awareness, perception and acceptance of the COVID-19 vaccines among the participants. Binomial logistic regression was used to evaluate the factors associated with willingness to accept COVID-19 vaccines and participate in immunisation programmes.

Results

The results indicate that COVID-19 vaccines are more likely to be used by adult Africans over the age of 18 who are largely technologically savvy (55 percent) if the vaccine is made broadly available. A total of 33 percent of those who responded said they were unlikely to receive the vaccine, with another 15 percent stating they were undecided. Aside from that, we found that vaccine hesitancy was closely associated with socio-demographic characteristics such as age, gender, education and source of information. We also found that there were widespread conspiracies and myths about the COVID-19 vaccines.

Conclusion

More than two-thirds of African adults who participated in the survey indicated they would not receive the COVID-19 vaccine, with majority of them expressing skepticisms about the vaccine’s efficacy. It is possible that many of the people who would not be vaccinated would have an impact on the implementation of a COVID-19 immunisation programme that is meant for all of society. Majority of the respondents were unwilling to pay for the COVID-19 vaccines when made available. An awareness campaign should be focused on promoting the benefits of vaccination at the individual and population levels, as well as on taking preemptive actions to debunk misconceptions about the vaccines before they become further widespread.
Efficacy and safety of GLP-1 receptor agonists versus SGLT-2 inhibitors in overweight/obese patients with or without diabetes mellitus: a systematic review and network meta-analysis
Authors: Ma Hong , Lin Yu-Hao , Dai Li-Zhen , Lin Chen-Shi , Huang Yanling , Liu Shu-Yuan
Published: February 2022

Objective

To compare the efficacy and safety between and within glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium-glucose co-transporter 2 inhibitors (SGLT-2is) in overweight or obese adults with or without diabetes mellitus.

Methods

PubMed, ISI Web of Science, Embase and Cochrane Central Register of Controlled Trials (CENTRAL) database were comprehensively searched to identify randomised controlled trials (RCTs) of effects of GLP-1RAs and SGLT-2is in overweight or obese participants from inception to Jan 16, 2022. The efficacy outcomes were the changes of body weight, glucose level and blood pressure. The safety outcomes were serious adverse events and discontinuation due to adverse events. The mean differences (MDs), odds ratios (ORs), 95% credible intervals (95% CI), the surface under the cumulative ranking (SUCRA) were evaluated for each outcome by network meta-analysis.

Results

Sixty-one RCTs were included in our analysis. Both GLP-1RAs and SGLT-2is conferred greater extents in body weight reduction, achieving at least 5% weight loss, HbA1c and fasting plasma glucose decrease compared with placebo. GLP-1RAs was superior to SGLT-2is in HbA1c reduction (MD: -0.39%, 95% CI: -0.70 to -0.08). GLP-1RAs had high risk of adverse events, while SGLT-2is were relatively safe. Based on intraclass comparison, semaglutide 2.4mg was among the most effective interventions in losing body weight (MD: -11.51kg, 95% CI: -12.83 to -10.21), decreasing HbA1c (MD: -1.49%, 95% CI: -2.07 to -0.92) and fasting plasma glucose (MD: -2.15mmol/L, 95% CI: -2.83 to -1.59), reducing systolic blood pressure (MD: -4.89mmHg, 95% CI: -6.04 to -3.71) and diastolic blood pressure (MD: -1.59mmHg, 95% CI: -2.37 to -0.86) with moderate certainty evidences, while it was associated with high risk of adverse events.

Conclusions

Semaglutide 2.4mg showed greatest effects on losing body weight, controlling glycemic level and reducing blood pressure while it was associated with high risk of adverse events.

ARTICLE SUMMARY

Strengths and limitations of this study

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The RoB 2.0 and GRADE methods were used to assess the risk of bias and evaluate the confidence in effect estimates.

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Study selection, data extraction, quality of study and evidence assessment were conducted independently by two authors and audited by the third author.

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The network meta-analysis was mostly based on indirect comparisons due to limited reported comparisons in available literatures.

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The small number of randomised controlled trials available in some comparisons.
Circulating polyunsaturated fatty acids and COVID-19: a prospective cohort study and Mendelian randomization analysis
Authors: Sun Yitang , Chatterjee Radhika , Ronanki Akash , Ye Kaixiong
Published: February 2022

Background

Higher circulating polyunsaturated fatty acids (PUFAs), especially omega-3 ones, have been linked to a better prognosis in patients of coronavirus disease 2019 (COVID-19). However, the effects and causality of pre-infection PUFA levels remain unclear.

Objective

To investigate the observational and causal associations of circulating PUFAs with COVID-19 susceptibility and severity.

Design

We first performed a prospective cohort study in UK Biobank, with 20,626 controls who were tested negative and 4,101 COVID-19 patients, including 970 hospitalized ones. Plasma PUFAs at baseline were measured by nuclear magnetic resonance, including total PUFAs, omega-3 PUFAs, omega-6 PUFAs, docosahexaenoic acid (DHA), linoleic acid (LA), and the omega-6/omega-3 ratio. Moreover, bidirectional two-sample Mendelian randomization (MR) analyses were performed to examine the causal associations of eight individual PUFAs, measured in either plasma or red blood cells, with COVID-19 susceptibility and severity using summary statistics from existing genome-wide association studies.

Results

In the observational association analysis, total PUFAs, omega-3 PUFAs, omega-6 PUFAs, DHA, and LA were associated with a lower risk of severe COVID-19. Omega-3 PUFAs and DHA were also associated with a lower risk of testing positive for COVID-19. The omega-6/omega-3 ratio was positively associated with risks of both susceptibility and severity. The forward MR analysis indicated that arachidonic acid (AA) and docosapentaenoic acid (DPA-n3) might be causally associated with a lower risk of severe COVID-19, with OR (95% CI) per one SD increase in the plasma level as 0.96 (0.94, 0.99) and 0.89 (0.81, 0.99), respectively. The reverse MR analysis did not support any causal effect of COVID-19 on PUFAs.

Conclusions

Our observational analysis supported that higher circulating PUFAs, either omega-3 or omega-6, are protective against severe COVID-19, while omega-3 PUFAs, especially DHA, were also associated with reducing COVID-19 susceptibility. Our MR analysis further supported causal associations of AA and DPA-n3 with a lower risk of severe COVID-19.
Factors Associated with Active Trachoma among Children in Ebinat District, South Gondar Zone, North West Ethiopia: A community-based cross-sectional study
Authors: Beyene Getalem Aychew , Beyene Nigist Aychew , Fekadu Gedefaw Abeje
Published: February 2022

Background

Despite the availability of effective prevention strategies and treatments, trachoma is still the major cause of infectious blindness worldwide. The majority of blindness from trachoma is currently reported from sub-Saharan Africa, with the greatest burden in Ethiopia. This study aimed to determine the prevalence and factors associated with active trachoma among children aged 1-9 years in Ebinat District.

Methods

A community-based cross-sectional study design was conducted in Ebinat District, South Gondar Zone, North West Ethiopia from March 1-30 2018. A multi-stage random cluster sampling technique was employed and all children 1–9 years old from the selected households were clinically examined for trachoma by ophthalmic nurses using the World Health Organization (WHO) simplified clinical grading scheme. A total of 565 children were included. Data were analyzed using SPSS. Multivariable logistic regression was used to identify factors associated with active trachoma among children.

Result

The overall prevalence of active trachoma was 36.1% (95% CI: 32.0% - 40.0%). Of all active trachoma cases, 26.5% and 9.6% were trachomatous follicular and trachomatous follicular-intense respectively. Discharge on the eye (AOR=8.23; 95% CI: 4.27-15.87), presence of liquid waste around the main house (AOR=2.31; 95% CI: 1.47-3.61), presence of human feces around the main house (AOR=2.64; 95% CI: 1.61-4.35), unclean faces (AOR= 5.71; 95% CI: 2.18 – 14.96), not washing face and hands frequently (AOR= 2.28; 95% CI: 1.33-3.90), not using soap while washing face and hands (AOR=1.95; 95% CI: 1.21-3.34), and having more flies on children’s face (AOR=1.74; 95% CI: 1.12-2.73) were significantly associated with active trachoma.

Conclusion and recommendation

Active trachoma is a major public health problem among children in the Ebinat District. Surgery for trichiasis, antibiotics for active disease, facial hygiene, and environmental improvement (SAFE) strategy at school and community are recommended to lower the burden of trachoma in the Ebinat District, Northwest Ethiopia.