bluuebunny/crossref_metadata_2025 huggingface dataset:
Kimura Disease of the Periorbita and Earlobe in a 15-Year-Old Male: A Case Report and Review of the Literature
Authors: Han Michael M. , Dermarkarian Christopher R. , Del Valle Estopinal Maria D. , Tao Jeremiah P.
Published: June 2022

Purpose:

The authors describe a case of Kimura disease (KD) affecting the lacrimal gland, the ipsilateral periorbita, and the contralateral earlobe. The authors also review the literature for characteristics and outcomes of KD affecting the periorbita or earlobe.

Methods:

The authors review retrospectively a single chart and abstract data from the English language literature.

Results:

A 15-year-old Samoan male presented with a left upper eyelid mass and later the contralateral earlobe and ipsilateral periorbita. Surgical resection was partially effective and normal vision and eye motility were maintained. Histopathology was consistent with KD. Thirty-seven cases of periorbital KD were identified in the literature. The average age of patients with periorbital KD was 31.9 years (standard deviation: 17.8 years), with 81.1% (30/37) of patients being male and 69.4% (25/36) Asian. Over half of periorbital KD patients had lacrimal gland involvement (51.3%; 19/37). Fifteen patients were initially treated with surgery; 3 (20%) had recurrence of the disease. Another 15 patients were initially treated with corticosteroids; 12 (80%) had recurrence of the disease. Ophthalmologic data, when reported, demonstrated that, most patients had no visual (77.8%; 14/18 patients) or motility disturbances (82.4%; 14/17 patients) but most had proptosis 71.4% (10/14). Only 4 cases of earlobe involvement in KD were identified, all in women.

Conclusions:

In the literature, orbital KD was rare but often affected the lacrimal gland and caused proptosis, commonly in young adult Asian males. Vision and extraocular motility were usually normal. Earlobe involvement was very rare. This unique case of KD that affected the orbit and contralateral earlobe corroborates the prior literature that KD is prone to recurrence but may not adversely affect vision or extraocular motility.
Testicular Torsion
Authors: Stoltzfus Lauren E. , Von Colln-Appling Christina , Infanti Mraz Megan A.
Published: June 2022

Testicular tuition is a genital urinary emergency that can lead to unfortunate patient outcomes. Care for these patients in a timely and effective manner will promote better patient outcomes. The purpose of this article is to discuss symptomology and clinical presentation of testicular torsion. Risk factors associated with testicular torsion and diagnostics are presented. Furthermore, emergent and effective nursing care in the preoperative, intraoperative, and postoperative processes is reviewed. Nursing implications as it relates to best practices and evidence-based care are presented for the nurse generalist and advanced practice nurse.
Complications of Endobronchial Valve Placement for Bronchoscopic Lung Volume Reduction
Authors: Low See-Wei , Swanson Karen L. , Lee Justin Z. , Tan Min-Choon , Cartin-Ceba Rodrigo , Sakata Kenneth K. , Maldonado Fabien
Published: June 2022

Background:

Patients with advanced emphysema experience breathlessness due to impaired respiratory mechanics and diaphragm dysfunction. Bronchoscopic lung volume reduction (BLVR) is a minimally invasive bronchoscopic procedure done to reduce hyperinflation and air trapping, promoting atelectasis in the targeted lobe and allowing improved respiratory mechanics. Real-world data on safety and complications outside of clinical trials of BLVR are limited.

Methods:

We queried the US Food and Drug Administrations (FDA) Manufacturers and User Device Experience database from May 2019 to June 2020 for reports involving BLVR with endobronchial valve (EBV) placement. Events were reviewed for data analysis.

Results:

We identified 124 cases of complications during BLVR with EBV implantation. The most-reported complication was pneumothorax (110/124, 89%), all of which required chest tube placement. A total of 54 of these cases (54/110, 49%) were complicated by persistent air leak requiring additional interventions. Repeat bronchoscopy was needed to remove the valves in 28 patients, 12 were discharged with a Heimlich valve, and 10 had an additional pleural catheter placed. The other complications of BLVR with EBV placement included respiratory failure (6/124, 5%), pneumonia (4/124, 3%), hemoptysis (2/124, 1.6%), valve migration (1/124, 1%), and pleural effusion (1/124, 1%). A total of 14 deaths were reported during that year.

Conclusion:

Pneumothorax is the most-reported complication for BLVR with EBV placement, and in 65% of cases, pneumothorax is managed without removing valves. Importantly, 14 deaths were reported during that timeframe. Further studies are needed to estimate the true magnitude of the complications associated with BLVR.
Five Versus 10 Pharyngeal Sprays of 10% Lignocaine for Topical Anesthesia During Flexible Bronchoscopy
Authors: Iyer Hariharan , Mishra Mayank , Sindhwani Girish , Mittal Saurabh , Tiwari Pawan , Hadda Vijay , Mohan Anant , Guleria Randeep , Madan Karan
Published: June 2022

Background:

Ensuring adequate patient comfort is crucial during bronchoscopy. Although lidocaine spray is recommended for topical pharyngeal anesthesia, the optimum dose of sprays is unclear. We compared 5 versus 10 sprays of 10% lidocaine for topical anesthesia during bronchoscopy.

Methods:

In this investigator-initiated, prospective, multicenter, randomized clinical trial, subjects were randomized to receive 5 (group A) or 10 sprays (group B) of 10% lidocaine. The primary objective was to compare the operator-rated overall procedure satisfaction between the groups.

Results:

Two hundred eighty-four subjects were randomized (143 group A and 141 group B). The operator-rated overall procedure satisfaction, VAS [mean (SD)] was similar between the groups [group A, 74.1 (19.9) and group B, 74.3 (18.5), P=0.93]. The VAS scores of patient-rated cough [group A, 32.5 (22.9) and group B, 32.3 (22.2), P=0.93], and operator-rated cough [group A, 29.8 (22.3) and group B, 26.9 (21.5), P=0.26] were also similar. The time to reach vocal cords, overall procedure duration, mean doses of sedatives, the proportion of subjects willing to return for a repeat procedure (if required), and complications were not significantly different. Subjects in group A received significantly less cumulative lidocaine (mg) [group A, 293.9 (11.6) and group B, 343.5 (10.6), P<0.001].

Conclusion:

During bronchoscopy, topical anesthesia with 5 sprays of 10% lidocaine is preferred as it is associated with a similar operator-rated overall procedure satisfaction at a lower cumulative lidocaine dose compared with 10 sprays.
Identifying and Investigating Ambulatory Care Sequences Before Invasive Coronary Angiography
Authors: Novelli Anna , Frank-Tewaag Julia , Bleek Julian , Günster Christian , Schneider Udo , Marschall Ursula , Schlößler Kathrin , Donner-Banzhoff Norbert , Sundmacher Leonie
Published: June 2022

Background:

The concept of care pathways is widely used to provide efficient, timely, and evidence-based medical care. Recently, the investigation of actual empirical patient pathways has gained attention. We demonstrate the usability of State Sequence Analysis (SSA), a data mining approach based on sequence clustering techniques, on comprehensive insurance claims data from Germany to identify empirical ambulatory care sequences. We investigate patients with coronary artery disease before invasive coronary angiography (CA) and compare identified patterns with guideline recommendations. This patient group is of particular interest due to high and regionally varying CA rates.

Methods:

Events relevant for the care of coronary artery disease patients, namely physician consultations and medication prescriptions, are identified based on medical guidelines and combined to define states. State sequences are determined for 1.5 years before CA. Sequence similarity is defined for clustering, using optimal matching with theory-informed substitution costs. We visualize clusters, present descriptive statistics, and apply logistic regression to investigate the association of cluster membership with subsequent undesired care events.

Results:

Five clusters are identified, the included patients differing with respect to morbidity, urbanity of residential area, and health care utilization. Clusters exhibit significant differences in the timing, structure, and extent of care before CA. When compared with guideline recommendations, 3 clusters show signs of care deficits.

Conclusions:

Our analyses demonstrate the potential of SSA for exploratory health care research. We show how SSA can be used on insurance claims data to identify, visualize, and investigate care patterns and their deviations from guideline recommendations.
Impacts of Bladder Managements and Urinary Complications on Quality of Life: Cross-sectional perspectives of persons with spinal cord injury living in Malaysia, Indonesia, and Thailand
Authors: Pattanakuhar Sintip , Ahmedy Fatimah , Setiono Steven , Engkasan Julia Patrick , Strøm Vegard , Kovindha Apichana
Published: June 2022

Background

The impact of bladder care and urinary complications on quality of life (QoL) in persons with spinal cord injury (SCI) who have neurogenic lower urinary tract dysfunction has not been elucidated, especially in those living in low-resource countries.

Methods

This multinational cross-sectional survey was conducted in rehabilitation facilities in Malaysia, Indonesia, and Thailand. Community-dwelling adults with traumatic or non-traumatic SCI participating in the International Spinal Cord Injury Community Survey (InSCI) from 2017 to 2018 were enrolled. Data regarding bladder management/care, presence of bladder dysfunction, urinary tract infection (UTI), and QoL score were extracted from the InSCI questionnaire. The impact of bladder care and urinary complications on QoL was determined using univariable and multivariable regression analysis.

Results

Questionnaires from 770 adults were recruited for analysis. After adjusting for all demographic and SCI-related data, secondary conditions, as well as activity and participation factors, UTI was an independent negative predictive factor of QoL score (p = 0.007, unstandardized coefficients = -4.563, multivariable linear regression analysis, enter method).

Conclusions

Among bladder care and urinary complication factors, UTI is the only factor negatively impacting QoL. These results address the importance of proper bladder management and UTI prevention in persons with SCI to improve their QoL.
How Did Patients Living With Immune-Mediated Rheumatic Diseases Face the Beginning of the COVID-19 Pandemic in Brazil? Results of the COnVIDa Study
Authors: Pugliesi Alisson , Sachetto Zoraida , de Medeiros Pinheiro Marcelo , Salviato Pileggi Gecilmara , Sarot Pereira da Cunha Gustavo , Hajar Faissal Nemer , Marques Negrisolli Cunha Maria Luiza , Henrique da Mota Licia Maria , Lopes Marques Claudia Diniz , Kakehasi Adriana Maria , Rodrigues Ferreira Wanda Heloísa , Araújo Nafice Costa , Monteiro Gomides Reis Ana Paula , Rodrigues de Abreu Vieira Rejane Maria , Ferreira Gilda Aparecida , Danowski Adriana , de Souza Viviane Angelina , Soares Egypto de Brito Danielle Christinne , dos Santos Paiva Eduardo , Provenza José Roberto , Feijó Azevedo Valderílio
Published: June 2022

Background

The coronavirus disease 2019 (COVID-19) pandemic has brought additional burden to patients living with immune-mediated rheumatic diseases (IMRDs), especially at the beginning of 2020, for which information for this population is lacking.

Methods

COnVIDa is a cross-sectional study on patients with IMRD from all regions of Brazil who were invited to answer a specific and customized Web questionnaire about how they were facing the COVID-19 pandemic, especially focusing on health care access, use of medications, and patient-reported outcomes related to IMRD activity. The questionnaire was applied from June 1 to 30, 2020.

Results

In total, 1722 of 2576 patients who answered the Web questionnaire were included in the final analysis. Participants were most frequently women, 56% were between 31 and 50 years old, and most (55%) has private health insurance. The most commonly reported IMRD was rheumatoid arthritis (39%), followed by systemic lupus erythematosus (28%). During the study period, 30.7% did not have access to rheumatology consultations, and 17.6% stopped chronic medications. Telemedicine was reported in 44.8% of patients.

Conclusion

COnVIDa demonstrated a negative impact on health care access and treatment maintenance of patients living with IMRD during the COVID-19 pandemic. However, it also presented an uptake of telemedicine strategies. Data presented in this study may assist future coping policies.
Magnetic Resonance Imaging Assessment of Right Ventricular Deformation in Patients With Transposition of the Great Arteries
Authors: Gregov Andrija , Hrabak Paar Maja
Published: June 2022

Purpose:

To detect changes of right ventricular (RV) myocardial deformation in patients with systemic RV (SRV) and transposition of the great arteries (TGA) as compared with individuals without structural heart disease.

Materials and Methods:

We performed a retrospective analysis of cine steady-state free precession cardiac magnetic resonance imaging sequences acquired using a 1.5 T scanner in short-axis and long-axis views in 25 patients with SRV (16 with atrial switch repair for D-TGA and 9 with congenitally corrected TGA; age range 19 to 68, 13 males). The control group consisted of 25 individuals without structural heart disease (age range 10 to 73, 14 males). Besides routine RV magnetic resonance imaging volumetry, mean longitudinal RV strain was measured on a 4-chamber view, and mean circumferential RV strain on 3 short-axis images (basal, midventricular, and apical) based on feature tracking. The strain parameters were statistically compared between patients with SRV and the control group.

Results:

Patients with SRV, compared with the control group, had significantly higher RV-indexed end-diastolic volume (122±40 vs. 70±9 mL/m2, P<0.001), lower RV ejection fraction (45±12% vs. 62±6%, P<0.001), and reduced mean longitudinal RV strain (−13.7±3.6% vs. −21.6±2.7%, P<0.001). There was no relevant difference between mean circumferential SRV strain in the basal and midventricular plane; however, in patients with SRV, mean circumferential strain was reduced at the apical level (−12.0±6.1% vs. −17.9±5.6%, P<0.001).

Conclusions:

SRV failure could be explained by reduced longitudinal SRV strain caused by the longitudinal orientation of RV myocardial fibers. In patients with SRV, circumferential RV strain is only reduced in apical segments.
Plasma cfDNA predictors of established bacteraemic infection
Authors: Urosevic Nadezda , Merritt Adam J. , Inglis Timothy J. J.
Published: June 2022

Introduction. Increased plasma cell-free DNA (cfDNA) has been reported for various diseases in which cell death and tissue/organ damage contribute to pathogenesis, including sepsis.

Gap Statement. While several studies report a rise in plasma cfDNA in bacteraemia and sepsis, the main source of cfDNA has not been identified.

Aim. In this study, we wanted to determine which of nuclear, mitochondrial or bacterial cfDNA is the major contributor to raised plasma cfDNA in hospital subjects with bloodstream infections and could therefore serve as a predictor of bacteraemic disease severity.

Methodology. The total plasma concentration of double-stranded cfDNA was determined using a fluorometric assay. The presence of bacterial DNA was identified by PCR and DNA sequencing. The copy numbers of human genes, nuclear β globin and mitochondrial MTATP8, were determined by droplet digital PCR. The presence, size and concentration of apoptotic DNA from human cells were established using lab-on-a-chip technology.

Results. We observed a significant difference in total plasma cfDNA from a median of 75 ng ml−1 in hospitalised subjects without bacteraemia to a median of 370 ng ml−1 (P=0.0003) in bacteraemic subjects. The copy numbers of nuclear DNA in bacteraemic also differed between a median of 1.6 copies µl−1 and 7.3 copies µl−1 (P=0.0004), respectively. In contrast, increased mitochondrial cfDNA was not specific for bacteraemic subjects, as shown by median values of 58 copies µl−1 in bacteraemic subjects, 55 copies µl−1 in other hospitalised subjects and 5.4 copies µl−1 in healthy controls. Apoptotic nucleosomal cfDNA was detected only in a subpopulation of bacteraemic subjects with documented comorbidities, consistent with elevated plasma C-reactive protein (CRP) levels in these subjects. No bacterial cfDNA was reliably detected by PCR in plasma of bacteraemic subjects over the course of infection with several bacterial pathogens.

Conclusions. Our data revealed distinctive plasma cfDNA signatures in different groups of hospital subjects. The total cfDNA was significantly increased in hospital subjects with laboratory-confirmed bloodstream infections comprising nuclear and apoptotic, but not mitochondrial or bacterial cfDNAs. The apoptotic cfDNA, potentially derived from blood cells, predicted established bacteraemia. These findings deserve further investigation in different hospital settings, where cfDNA measurement could provide simple and quantifiable parameters for monitoring a disease progression.
Chromobacterium alticapitis sp. nov. and Chromobacterium sinusclupearum sp. nov. isolated from wild cranberry bogs in the Cape Cod National Seashore, USA
Authors: O'Hara-Hanley Kory , Harrison Alisha , Soby Scott D.
Published: June 2022

Two non-pigmented strains in the genus

Chromobacterium

, MWU14-2602T and MWU13-2610T, were isolated from wild cranberry bogs in the Cape Cod National Seashore, USA. The isolates were characterized by genomic and phenotypic analyses, the results of which indicated that they represent two novel species. Based on total genome sequences, the closest relatives were in the

Chromobacterium amazonense

group, which includes the recently described

Chromobacterium paludis

. Whole genome sequences were compared by genome blast distance phylogeny, digital DNA–DNA hybridization and average nucleotide identity analyses with each other and with the type strains of their nearest species. MWU14-2602T and MWU13-2610T fell well below the accepted cutoff values for species relatedness, clearly indicating that they represent novel species. Although little is known about these organisms in situ, under laboratory conditions, MWU13-2610T produced a modest amount of HCN and was strongly positive for exoprotease activity, whereas MWU14-2602T did not produce HCN or exoproteases. The predominant fatty acids for both isolates were summed C16 : 1ω7cis/C16 : 1ω6cis. Both isolates produced siderophores and pyomelanin pigment on rich media, and neither was haemolytic on sheep blood agar. We propose the names Chromobacterium alticapitis sp. nov. (type strain MWU14-2602T=ATCC TSD 260T=CCOS 1979T) and Chromobacterium sinusclupearum sp. nov. (type strain MWU13-2610T=ATCC TSD-259T=CCOS 1981T) for these taxa.
RshA mutations contributing to tigecycline resistance in Mycobacteroides abscessus
Authors: Aw Kar Men , Ng Hien Fuh , Lee Col Lin , Zin Thaw , Ngeow Yun Fong
Published: June 2022

Tigecycline is an important rescue antibiotic for many bacterial infections. In

Mycobacteroides abscessus

, tigecycline resistance has been associated with dysregulated stress response caused by aberrations in the interaction of the SigH and RshA factors. In this study, two tigecycline-resistant mutants of

M. abscessus

(CL5A and CL6A) with mutations in the rshA gene were studied using gene complementation, RT-qPCR and the bacterial adenylate cyclase two-hybrid (BACTH) system. The results supported the premise that mutations in the rshA interrupt the RshA–SigH interaction to cause the overexpression of the sigH gene that leads to tigecycline resistance or reduced susceptibility.
Genetic correlates of vitamin D-binding protein and 25 hydroxyvitamin D in neonatal dried blood spots
Authors: Albiñana Clara , Zhu Zhihong , Borbye-Lorenzen Nis , Boelt Sanne Grundvad , Cohen Arieh S. , Skogstrand Kristin , Wray Naomi R. , Revez Joana A. , Privé Florian , Petersen Liselotte V. , Bulik Cynthia M. , Plana-Ripoll Oleguer , Musliner Katherine L. , Agerbo Esben , Børglum Anders D. , Hougaard David M. , Nordentoft Merete , Werge Thomas , Mortensen Preben Bo , Vilhjálmsson Bjarni J. , McGrath John J.
Published: June 2022

The vitamin D binding protein (DBP), encoded by the group-specific component (GC) gene, is a much-studied component of the vitamin D system. In a genome-wide association study of DBP concentration in 65,589 neonates, we identified 26 independent loci, 17 of which were in or close to the GC gene, with fine-mapping identifying 2 loci on chromosomes 12 and 17 (missense variants within SH2B3 and GSDMA, respectively). When adjusted for key GC haplotypes, we found 15 independent loci distributed over 10 chromosomes. Mendelian randomization analyses found evidence consistent with a unidirectional, causal effect of higher DBP concentration and (a) higher 25 hydroxyvitamin D (25OHD) concentration, and (b) a reduced risk of multiple sclerosis and rheumatoid arthritis. A phenome-wide association study in an external dataset confirmed that higher DBP concentration was associated with higher 25OHD concentration and a reduced risk of vitamin D deficiency. Our study provides new insights into the influence of DBP on vitamin D status and a range of health outcomes.
A systems serology analysis of correlates of protection against cholera
Authors: Wiens Kirsten E. , Iyer Anita S. , Bhuiyan Taufiqur R. , Lu Lenette L. , Cizmeci Deniz , Gorman Matthew J. , Yuan Dansu , Becker Rachel L. , Ryan Edward T. , Calderwood Stephen B. , LaRocque Regina C. , Chowdhury Fahima , Khan Ashraful I. , Levine Myron M. , Chen Wilbur H. , Charles Richelle C. , Azman Andrew S. , Qadri Firdausi , Alter Galit , Harris Jason B.
Published: June 2022

Vibriocidal antibodies are the best characterized correlate of protection against cholera and are used to gauge immunogenicity in vaccine trials. However, there is no vibriocidal titer threshold associated with absolute protection against infection with Vibrio cholerae or with symptomatic disease in infected individuals. While other circulating antibody responses have also been associated with a decreased risk of V. cholerae infection, there has been no comprehensive comparison of correlates of protection against cholera. To address this, we analyzed 58 serum antibody biomarkers as correlates of protection against both V. cholerae infection and against cholera diarrhea in infected individuals. The study was performed in two cohorts: (1) household contacts of patients with cholera in Bangladesh, and (2) North American volunteers who were vaccinated with a single dose of CVD 103-HgR live oral cholera vaccine and then challenged with virulent V. cholerae O1 El Tor Inaba. In household contacts, we identified 20 antibody markers that were correlated with protection against V. cholerae infection, though there was overlap between distributions. Conditional random forest models identified serum antibody-dependent complement deposition, targeting the V. cholerae O1 antigen, as the most predictive individual correlate of protection from infection, while vibriocidal antibody titers were less predictive. The model that most accurately predicted protection from infection included five biomarkers, with a cross-validated area under the curve (cvAUC) of 79% (95% CI 73-85). Similarly, in North American volunteers who were challenged with V. cholerae after vaccination, a different five-biomarker model predicted protection from the development of cholera diarrhea with a cvAUC of 78% (95% CI 66-91). Thus, while several new biomarkers predict protection better than vibriocidal titers, it remains difficult to consistently predict whether an individual will be protected from future mucosal infection or symptoms using current serologic markers.
Alternative nutritional and clinical care practices for NEC prevention drive distinct profiles and functional responses in the preterm gut microbiome
Authors: Neumann Charlotte J , Mahnert Alexander , Kumpitsch Christina , Kiu Raymond , Dalby Matthew J , Kujawska Magdalena , Madl Tobias , Kurath-Koller Stefan , Urlesberger Berndt , Resch Bernhard , Hall Lindsay J , Moissl-Eichinger Christine
Published: June 2022

Preterm infants with very low birthweight are at serious risk for necrotizing enterocolitis. To functionally analyse the principles of three successful preventive NEC regimens, we characterized faecal samples of 54 infants (< 1,500 g, n = 383) longitudinally (two weeks) with respect to gut microbiome profiles (bacteria, archaea, fungi, viruses), microbial function, virulence factors, antibiotic resistances and metabolic profiles, including human milk oligosaccharides (HMOs) and short-chain fatty acids. Probiotic Bifidobacterium longum ssp. infantis supplementation affected microbiome development globally, pointing toward the genomic potential to convert HMOs. Engraftment of Bifidobacterium substantially reduced microbiome-associated antibiotic resistance as compared to regimens using probiotic Lactobacillus rhamnosus or no supplementation. Crucially, the beneficial effects of Bifidobacterium supplementation depended on simultaneous feeding with HMOs. We demonstrate that preventive regimens have the highest impact on early maturation of the gastrointestinal microbiome, enabling the establishment of a resilient microbial ecosystem that reduces pathogenic threats in at-risk preterm infants.
Side effects of Covishield vaccine among frontline healthcare workers of a tertiary health care center
Authors: Dhungana Durga , Regmi Yukta Narayan , Shrestha Deependra , Thapa Krishna , Pun Chandra Bahadur , Upadhayaya Tirthalal , Hirachan Gopi
Published: June 2022

Objectives

COVID disease started in the late 2019 and within a short time became a pandemic disease. With the increasing morbidity and mortality all over the world and the therapeutics not doing wonders, scientists were in the attempt to develop vaccines as a mitigating measure. With continuous efforts and developments, different vaccines were developed and rolled out gradually in different countries. Concerns were notable for occurrence of side effects. Hence this study was done to assess the side effects following Covishield vaccination in Nepal at the initial stage.

Methods

This was a cross-sectional study done via snowball sampling method among healthcare workers at a tertiary medical college hospital in Pokhara, Nepal after obtaining ethical consent from the institutional review committee of the concerned hospital. The proforma was sent via online means through different social media platforms and also printed forms were also given to the respondents. A total of 139 respondents were obtained after removing duplications. The data were entered into SPSS and analyzed using descriptive and inferential statistics. P-value ≤ 0.05 was considered statistically significant.

Results

Majority (64.7%) were female healthcare workers. More than half (52.3%) used pre-medication in an attempt to avoid the side effects of vaccine. Most (90.6%) reported at least one side effect-local or systemic to the first dose and approximately three-quarter (74.3%) reported side effect to the second dose. Common side effects were pain at injection site, muscle pain, headache, fatigue and weakness. Most of the side effects were higher with the first dose as compared to the second dose.

Conclusion

Side effects are common with Covishield vaccination, significantly more with the first dose as compared to the second dose. Female gender, younger age and past covid infection were associated with slightly more occurrence of side effects; however were not found to be statistically significant.
Statistical Analysis Plan for the Bedside Ultrasound Conducted in Kids with distal upper Limb fractures in the Emergency Department (BUCKLED) trial
Authors: Jones Philip M , Keijzers Gerben , Byrnes Joshua , Ware Robert S , Snelling Peter J
Published: June 2022

Background

The Bedside Ultrasound Conducted in Kids with distal upper Limb fractures in the Emergency Department (BUCKLED) trial is a multicentre, randomised, open-label, non-inferiority study comparing point-of-care ultrasound to x-ray as the initial imaging modality in children with clinically non-angulated distal forearm injuries.

Objective

The purpose of this document is to minimise bias by defining and making publicly available our analysis approach prior to completing the study and reviewing or analysing the trial data.

Methods

We developed a statistical analysis plan (SAP) for reporting and analysing the BUCKLED trial including our approach to expected protocol deviations, withdrawals, missing data, and loss to follow up. Study methods are described using a previously published study protocol. Broad statistical analysis principles are outlined. Primary and secondary trial outcomes are described, along with appropriate methods for statistical comparison.

Results

This report pre-specifies the SAP for the primary outcome of upper limb function at 4 weeks, using an intention-to-treat analysis with a hypothesis of non-inferiority. Results of a per-protocol analysis will also be reported. Subgroup analyses will include diagnostic category and age category and secondary outcomes will include cost, quality of life, satisfaction, pain, adverse events, rates of imaging, Emergency Department length of stay, treatment time and diagnostic accuracy. Methods of statistical comparison are outlined.

Conclusion

This report describes the SAP for the BUCKLED trial, to minimise analysis bias and ensure transparency and internal validity for the findings of this randomised controlled trial.
The association of child marriage with morbidities and mortality among children under 5 years in Afghanistan: Findings from a national survey
Authors: Dadras Omid , Hazratzai Mohammadsediq , Dadras Fateme
Published: June 2022

Background

There is still a gap in knowledge of the impact that child marriage could have on the mortality and morbidity of children in Afghanistan. This study used the data from the latest Afghanistan demographic health survey conducted in 2015 (ADHS) to address this gap and advance the current knowledge.

Methods

A secondary analysis of the 2015 ADHS, including the births in the past 5 years to ever-married women aged 15-24 years old, was carried out. Logistic regression analyses were employed to examine the association of child marriage (<18y) with morbidities (diarrhea, acute respiratory infection, and fever in the last 2 weeks), mortality (neonatal, infant, child), and size at birth among the children under 5 born to women aged 15-24 years, before and after adjusting for the effect of sociodemographic and structural inequalities.

Results

Approximately two-thirds of births in the past 5 years belong to 15-24 years old mothers who married at ages <18. The majority of them were born to mothers residing in rural areas (75.67%) with no education (51.68%) from poor households (39.39%). As compared to the births to women married at ages ≥18, there was a significantly higher likelihood of neonatal mortality among births to women married at ages <18 (crude OR = 2.30, 95% CI: 1.52-3.49 & adjusted OR = 1.94, 95% CI: 1.25-3.01) and higher infant mortality among the births to the women married at ages ≤14y (crude OR = 1.94, 95% CI: 1.06-3.53). However, it disappeared for neonatal mortality after adjustment for adequacy of antenatal care (ANC) and infant mortality after adjustment for sociodemographic inequalities.

Conclusion

Although the births to women married as a child (<18) were more likely to die at an early age, this association disappeared after adjustment for the adequacy of ANC. Given the unavoidable practice of child marriage in Afghanistan, this finding emphasizes the importance of providing adequate ANC for young brides to prevent child mortality. In addition, strong global advocacy is required to empower and support young Afghan women in negotiating their reproductive and maternity rights with their partners by reducing social and gender-based inequalities.
Immunosuppression as a hub for SARS-CoV-2 mutational drift
Authors: Shapira Guy , Patalon Tal , Gazit Sivan , Shomron Noam
Published: June 2022

Newly emerging SARS-CoV-2 variants of concern (VOCs) play a major role in the persistence of the coronavirus disease 2019 (COVID-19) pandemic. While these VOCs are characterized by extraordinary evolutionary leaps and evasion from previously acquired immunity, their origins remain mostly unknown. In this study, we paired electronic health records of individuals infected with SARS-CoV-2 to viral whole-genome sequences, to assess effects of host clinical parameters and immunity on the intra-host evolution of SARS-CoV-2. We found small, albeit significant differences in SARS-CoV-2 intra-host diversity, which depended on host parameters such as vaccination status and smoking. Viral genomes showed a significant difference in the early course of disease in only one of 31 immunosuppressed patients, a recently vaccinated woman aged in her 70s. We highlight the unusually mutated viral genome obtained from this woman, which harbored near-complete truncating of the accessory protein ORF3a. Our findings suggest only minor influence of host parameters on the SARS-CoV-2 intra-host evolutionary rate and trajectory, with even the majority of immunosuppressed persons carrying fairly unremarkable viral genomes. We hypothesize that major evolutionary steps, such as those observed in VOCs, are rare occurrences, even among immunodeficient hosts.

Highlights

Intra-host viral diversity is modestly affected by host clinical parameters, such as vaccination status and smoking.

The emergence and fixation of high-impact SARS-CoV-2 mutations in immunosuppressed hosts are rare, and not exclusive to patients with prolonged viral shedding.

We identified a rare stop-gain mutation, leading to near-complete truncating of ORF3a, in an immunosuppressed woman recently vaccinated against COVID-19.
American Covid: An Econometric Analysis of Variants
Authors: McIntosh James
Published: June 2022

Covid-19 time series data on new cases from the United States for the period January 20, 2020 to February 7, 2022 is analyzed using a distributed lag econometric model applied to the Wild Type, Alpha, and Delta variants to determine the relative efficacy of vaccines and previous infection induced immunity. The results from this study confirm, for the most part, what others have found using large cross section samples: vaccines are effective in dealing with all three variants, more so with Delta. Infection induced immunity is always greater than or equal that delivered by a vaccination and is largest for the Delta variant. However, in the Delta case previous non-Delta infections had no prophylactic value in preventing new Delta infections.
HEALTHCARE UTILISATION IN PATIENTS WITH LONG-TERM CONDITIONS DURING THE COVID-19 PANDEMIC: A POPULATION BASED STUDY ACROSS GREATER MANCHESTER, UK
Authors: Sammut-Powell Camilla , Williams Richard , Sperrin Matthew , Thomas Owain , Peek Niels , Grant Stuart W.
Published: June 2022

Background

The COVID-19 pandemic has placed an unprecedented demand on global healthcare resources. Data on whole population healthcare utilisation (HCU) across both primary and secondary care during the COVID-19 pandemic are lacking.

Aim

To describe primary and secondary HCU stratified by LTCs and deprivation, during the first 19 months of COVID-19 pandemic across a large urban area in the United Kingdom.

Methods

Observational HCU data between 30th-December-2019 and 1st-August-2021 were extracted from the Greater Manchester Care Record. Primary care HCU (incident prescribing and recording of healthcare information) and secondary care HCU (planned and unplanned admissions) were assessed.

Results

The first national lockdown was associated with reductions in all primary HCU measures, ranging from 24.7% (24.0% to 25.5%) for incident prescribing to 84.9% (84.2% to 85.5%) for cholesterol monitoring. Secondary HCU also dropped significantly for planned (47% (42.9% to 51.5%)) and unplanned admissions (35.0% (28.3% to 41.6%)). Only secondary care had significant reductions in HCU during the second national lockdown. Primary HCU measures had not recovered to pre-pandemic levels by the end of the study. The secondary admission rate ratio between multi-morbid patients and those without LTCs increased during the first lockdown by a factor of 2.4 (2.0 to 2.9;p<0.001) for planned admissions and by 1.3 (1.1 to 1.5;p=0.006) for unplanned admissions. No significant changes in this ratio were observed in primary HCU. Different patterns in secondary care HCU were observed by LTC group.

Conclusion

Major changes in primary and secondary HCU have been observed during the COVID-19 pandemic. Secondary HCU reduced more in those without LTCs and the ratio of utilisation between the most and least deprived increased for the majority of HCU measures. Overall primary HCU measures and secondary care HCU for some LTC groups had not returned to pre-pandemic levels by the end of the study.
Tau and α-synuclein shape microtubule organization and microtubule-dependent transport in neuronal dendrites
Authors: Rierola Marina , Trushina Nataliya I. , Monteiro-Abreu Nanci , Conze Christian , Holtmannspötter Michael , Kurre Rainer , Holzer Max , Arendt Thomas , Heinisch Jürgen J. , Brandt Roland , Bakota Lidia
Published: June 2022

Tau and α-synuclein are major players in neurodegenerative diseases, but their physiological role, particularly in dendrites, is poorly understood. Here we show that, surprisingly, lack of tau protein induces the development of a more elaborate dendritic arbor of hippocampal pyramidal cells in organotypic tissue. Using high-speed volumetric lattice light-sheet microscopy and single particle tracking, we found a more directional KIF1A-mediated transport in dendrites of Tau KO cells. Increased transport processivity correlated with longer and straighter dendritic microtubules as revealed by three-dimensional super-resolution microscopy of cultured hippocampal neurons. Unbiased mass spectrometric analysis of tissue showed highly increased expression of α-synuclein in Tau KO hippocampi. Overexpression of α-synuclein mimicked the transport characteristics observed in Tau KO cells. Our data indicate that tau and α-synuclein shape microtubule-dependent transport in neuronal dendrites, thereby promoting dendritic arborization during maturation. Furthermore, the data demonstrate that transport efficiency and length and straightness of microtubules are correlated.
Saturation genome editing of DDX3X clarifies pathogenicity of germline and somatic variation
Authors: Radford E.J. , Tan H.K. , Andersson M.H.L. , Stephenson J.D , Gardner E.J. , Ironfield H. , Waters A.J. , Gitterman D. , Lindsay S. , Abascal F. , Martincorena I. , Kolesnik A. , Ng-Cordell E. , Firth H.V. , Baker K. , Perry J.R.B. , Adams D.J. , Gerety S.S. , Hurles M.E.
Published: June 2022

Loss-of-function ofDDX3Xis a leading cause of neurodevelopmental disorders (NDD) in females.DDX3Xis also a somatically mutated cancer driver gene proposed to have tumour promoting and suppressing effects. We performed saturation genome editing ofDDX3X,testingin vitrothe functional impact of 12,776 nucleotide variants. We identified 3,432 functionally abnormal variants, in three distinct classes. We trained a machine learning classifier to identify functionally abnormal variants of NDD-relevance. This classifier has at least 97% sensitivity and 99% specificity to detect variants pathogenic for NDD, substantially out-performingin silicopredictors, and resolving up to 93% of variants of uncertain significance. Moreover, functionally-abnormal variants could account for almost all of the excess nonsynonymousDDX3Xsomatic mutations seen inDDX3X- driven cancers. Systematic maps of variant effects generated in experimentally tractable cell types have the potential to transform clinical interpretation of both germline and somatic disease-associated variation.
Synaptic proteomics reveal distinct molecular signatures of cognitive change andC9ORF72repeat expansion in the human ALS cortex
Authors: Laszlo Zsofia I. , Hindley Nicole , Sanchez Avila Anna , Kline Rachel A. , Eaton Samantha L. , Lamont Douglas J. , Smith Colin , Spires-Jones Tara L. , Wishart Thomas M. , Henstridge Christopher M.
Published: June 2022

The two major hypotheses of Amyotrophic Lateral Sclerosis (ALS) pathogenesis (dying-forward and dying-back) have synapses at their core. Furthermore, increasing evidence suggests synaptic dysfunction is a central and possibly triggering factor in ALS. Despite this, we still know very little about the molecular profile of an ALS synapse. To address this gap, we designed a synaptic proteomics experiment to perform an unbiased assessment of the synaptic proteome in the ALS brain. We isolated synaptoneurosomes from fresh-frozen post-mortem human cortex (11 controls and 18 ALS) and stratified the ALS group based on cognitive profile (Edinburgh Cognitive and Behavioural ALS Screen (ECAS score)) and presence of aC9ORF72hexanucleotide repeat expansion (C9ORF72-RE). This allowed us to assess regional differences and the impact of phenotype and genotype on the synaptic proteome, using Tandem Mass Tagging-based proteomics. We identified over 6000 proteins in our synaptoneurosomes and using robust bioinformatics analysis we validated the strong enrichment of synapses. We found more than 30 ALS-associated proteins at the synapse, including TDP-43, FUS, SOD1 and C9ORF72. We identified almost 500 proteins with altered expression levels in ALS synapses, with region-specific changes highlighting proteins and pathways with intriguing links to neurophysiology and pathology. Stratifying the ALS cohort by cognitive status revealed almost 150 specific alterations in cognitively impaired ALS synapses, highlighting novel synaptic proteins that may underlie the synaptic vulnerability in these patients. Stratifying byC9ORF72-RE status revealed 330 protein alterations in theC9ORF72-RE+ve group, with KEGG pathway analysis highlighting strong enrichment for postsynaptic dysfunction, related to glutamatergic receptor signalling. We have validated some of these changes by western blot and at a single synapse level using array tomography imaging. In summary, we have generated the first unbiased map of the human ALS synaptic proteome, revealing novel insight into this key compartment in ALS pathophysiology and highlighting the influence of cognitive decline andC9ORF72-RE on synaptic composition.
Exploring the knowledge and acceptance of reputed Authorship Criteria: A Pilot Study among medical researchers in India
Authors: Bansal Bhavik
Published: June 2022

Objectives

To determine knowledge and acceptance of authorship criteria among residents, PhD scholars and faculty involved in medical research in India.

Design

A cross sectional survey was performed via Google forms (a web based platform).

Results

A total of 117 participants responded to the survey, of whom 66 (56%) were faculty/professors, 23 (20%) residents and 28 (24%) PhD scholars. 33% respondents had faced conflicts with their guide, 58% respondents have offered honorary authorship sometime in their careers. Only half of the respondents were aware of the ICMJE guidelines for authorship.

Conclusions

Gift Authorship and ‘pressure to publish’ are largely prevalent in bio medical research in India. Journals requiring author-contribution declarations, overlooking the number of publications as the sole source of offering academic promotions among others are possible solutions to curb this problem.
Radiographic Assessment of Lung Edema (RALE) Scores are Highly Reproducible and Prognostic of Clinical Outcomes for Inpatients with COVID-19
Authors: Al-Yousif Nameer , Komanduri Saketram , Qurashi Hafiz , Korzhuk Anatoliy , Lawal Halimat O. , Abourizk Nicholas , Schaefer Caitlin , Mitchell Kevin J. , Dietz Catherine M. , Hughes Ellen K. , Brandt Clara S. , Fitzgerald Georgia M. , Joyce Robin , Chaudhry Asmaa S. , Kotok Daniel , Rivera Jose D. , Kim Andrew I. , Shettigar Shruti , Lavina Allen , Girard Christine E. , Gillenwater Samantha R. , Hadeh Anas , Bain William , Shah Faraaz A. , Bittner Matthew , Lu Michael , Prendergast Niall , Evankovich John , Golubykh Konstantin , Ramesh Navitha , Jacobs Jana J. , Kessinger Cathy , Methé Barbara , Lee Janet S. , Morris Alison , McVerry Bryan J. , Kitsios Georgios D.
Published: June 2022

INTRODUCTION

Chest imaging is necessary for diagnosis of COVID-19 pneumonia, but current risk stratification tools do not consider radiographic severity. We quantified radiographic heterogeneity among inpatients with COVID-19 with the Radiographic Assessment of Lung Edema (RALE) score on Chest X-rays (CXRs).

METHODS

We performed independent RALE scoring by ≥2 reviewers on baseline CXRs from 425 inpatients with COVID-19 (discovery dataset), we recorded clinical variables and outcomes, and measured plasma host-response biomarkers and SARS-CoV-2 RNA load from subjects with available biospecimens.

RESULTS

We found excellent inter-rater agreement for RALE scores (intraclass correlation co-efficient=0.93). The required level of respiratory support at the time of baseline CXRs (supplemental oxygen or non-invasive ventilation [n=178]; invasive-mechanical ventilation [n=234], extracorporeal membrane oxygenation [n=13]) was significantly associated with RALE scores (median [interquartile range]: 20.0[14.1-26.7], 26.0[20.5-34.0] and 44.5[34.5-48.0], respectively, p<0.0001). Among invasively-ventilated patients, RALE scores were significantly associated with worse respiratory mechanics (plateau and driving pressure) and gas exchange metrics (PaO2/FiO2 and ventilatory ratio), as well as higher plasma levels of IL-6, sRAGE and TNFR1 levels (p<0.05). RALE scores were independently associated with 90-day survival in a multivariate Cox proportional hazards model (adjusted hazard ratio 1.04[1.02-1.07], p=0.002). We validated significant associations of RALE scores with baseline severity and mortality in an independent dataset of 415 COVID-19 inpatients.

CONCLUSION

Reproducible assessment of radiographic severity revealed significant associations with clinical and physiologic severity, host-response biomarkers and clinical outcome in COVID-19 pneumonia. Incorporation of radiographic severity assessments may provide prognostic and treatment allocation guidance in patients hospitalized with COVID-19.
Disentangling the common genetic architecture and causality of rheumatoid arthritis and systemic lupus erythematosus with COVID-19 outcomes: genome-wide cross trait analysis and bi-directional Mendelian randomization study
Authors: Yao Minhao , Huang Xin , Guo Yunshan , Zhao Jie V. , Liu Zhonghua
Published: June 2022

COVID-19 may cause a dysregulation of the immune system and has complex relationships with multiple autoimmune diseases, including rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). However, little is known about their common genetic architecture. We analysed summary-level genetic data from the latest COVID-19 host genetics consortium and consortia on RA and SLE to examine the shared genetic etiology and causal relationship between COVID-19 and RA/SLE. The cross-trait meta-analysis identified 46, 47, and 19 shared genetic loci for severe COVID-19, COVID-19 hospitalization, and SARS-CoV-2 infection with RA, and 19, 24, and 11 shared loci with SLE, respectively. Shared genes were significantly enriched in the spleen, lung, whole blood, and small intestine, and involved in immune function, inflammation and coagulation process. Co-localization analysis identified eight shared loci in TYK2, IKZF3, COL11A2, PSORS1C1, MANEAL and COG6 genes for COVID-19 with RA, and four in CRHR1, FUT2 and NXPE3 genes for COVID-19 with SLE. Bi-directional Mendelian randomization analysis suggested RA is associated with a higher risk of COVID-19 hospitalization, and COVID-19 is not related to RA or SLE. Our novel findings improved the understanding of the common genetic aetiology shared by COVID-19, RA and SLE, and suggested an increased risk of COVID-19 hospitalization in people with higher genetic liability to RA.