bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparison of Myopia Progression among Myopic Children with Intermittent Exotropia and No Strabismus
Authors: Kim Suzie , Babiuch Allison , Xiao Huijun , Williamson Alexandra
Published: August 2023

Significance

Myopia is a highly prevalent condition in the pediatric population that is commonly comorbid with intermittent exotropia. Our study found a trend towards significance in the reduction of myopia progression with strabismus correction surgery. Further investigations characterizing the interaction between myopia and strabismus may help inform future management guidelines.

Purpose

This study describes and compares myopic progression in the pediatric population with and without intermittent exotropia and its interaction with corrective strabismus surgery.

Methods

This study analyzes a retrospective cohort of 1,239 pediatric myopic patients who were evaluated by pediatric ophthalmologists and optometrists at a tertiary care center from 2012 to 2020. The main outcome measures were the trends in refractive error over time in those with and without intermittent exotropia as well as trends in those who did and did not undergo strabismus surgery.

Results

275 (22%) patients were identified to have intermittent exotropia and 12 (4.4%) of this group underwent surgical correction in the study period. No statistically significant difference was identified in myopic progression between those with intermittent exotropia and those without strabismus and no difference was found in mean annual spherical equivalent change between intermittent exotropia patients who did not undergo surgery compared to those who did.

Conclusions

Pediatric myopic patients generally experience progression in the condition for several years independent of concurrent intermittent exotropia. Corrective strabismus surgery was not found to alter the natural history of myopia in children, though a reduction in myopic progression in surgically treated patients trended towards significance. Increases in the prevalence of different treatment strategies will necessitate further studies to determine best practices for this population.
Comparison of 68Ga-DOTA-FAPI-04 and 18F-FDG PET/CT in Patients With SAPHO Syndrome
Authors: Wang Peipei , Li Chen , Hou Guozhu , Li Zhaohui , Jing Hongli , Zhang Wen , Li Fang
Published: August 2023

Purpose

Synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome is a rare inflammatory disorder of bone, joints, and skin, with various stages of bone lesions including inflammation and bone marrow fibrosis. Because the inflammation-induced fibrosis and bone marrow fibrosis are important features in SAPHO syndrome, we undertook a prospective investigation to evaluate whether PET/CT with 68Ga-DOTA-FAPI-04, a novel PET agent targeting fibroblast activation protein, was useful in the evaluation of the patients with SAPHO syndrome.

Patients and Methods

68Ga-DOTA-FAPI-04 PET/CT was performed on a cohort of 21 patients with known SAPHO syndrome. All patients underwent 68Ga-DOTA-FAPI-04 and 18F-FDG PET/CT on 2 consecutive days. The positive rates of the PET/CT scans at the sites of the osteoarticular symptom, the uptake values, and agreement with clinical osteoarticular symptom were compared.

Results

A total of 38 sites of involvement were detected. 18F-FDG PET/CT revealed 28 lesions. In contrast, 68Ga-DOTA-FAPI-04 PET/CT detected not only all lesions shown on 18F-FDG PET/CT but additional 10 lesions. 68Ga-DOTA-FAPI-04 scan also demonstrated significantly higher uptake and target-to-background ratio than 18F-FDG studies in the skeletal involvements. The agreement between 68Ga-DOTA-FAPI-04–positive lesions and current osteoarticular lesions was substantial (κ = 0.79, P < 0.001), whereas 18F-FDG had low to moderate agreement with clinical symptoms (κ = 0.52, P < 0.001).

Conclusions

68Ga-DOTA-FAPI-04 has potential as a promising imaging agent for the evaluation of SAPHO syndrome.
No Association of Preablation Thyroglobulin Antibody Positivity and Outcome in Pediatric Patients With Papillary Thyroid Carcinoma
Authors: Xu Yangmengyuan , Shi Lei , Wu Jie , Li Huilan , Wang Yu , Liu Bin
Published: August 2023

Objective

This multicenter study was designed to evaluate the relationship between preablation thyroglobulin antibody (TgAb) positivity and clinical outcomes in pediatric patients with papillary thyroid carcinoma (PTC).

Methods

In the period 2005–2020, all consecutive PTC patients 18 years or younger who underwent total thyroidectomy and radioiodine ablation at 3 tertiary hospitals in southwestern China were retrospectively included. Thyroglobulin antibody was measured before remnant ablation. Tumor characteristics and long-term outcomes were compared between TgAb-positive and TgAb-negative patients.

Results

One hundred thirty-two patients were analyzed. Preablation TgAb positivity was presented in 37.1% of patients. Tumor characteristics, lymph node metastases, and median duration of follow-up were similar between TgAb-positive and -negative patients. During follow-up, the percentage of patients with either surgical reintervention for lymph node metastases (4.1% vs 4.8%, P = 1.000) or repeated 131I therapy (14.3% vs 20.5%, P = 0.373) was similar between TgAb-positive and -negative patients. At the final follow-up visit, the rates of structural disease did not differ between the 2 groups (6.1% vs 4.8%, P = 0.710).

Conclusions

This multicentric study highlights no association of preablation TgAb positivity and clinical outcome in pediatric patients with PTC.
Application of Ultrasound Shear Wave Elastography Combined With BRAFV600E Mutation for the Diagnosis of Papillary Thyroid Carcinoma
Authors: Xu Li , Haitao Ran , Li Zhou
Published: August 2023

This prospective study aimed to investigate the combination of shear wave elastography (SWE) and BRAFV600E mutation testing for the diagnosis of papillary thyroid carcinoma (PTC). One hundred thyroid nodules with an American College of Radiology thyroid imaging reporting and data system classification of 4 or 5 were subjected to SWE measurement, BRAFV600E genotyping, fine-needle aspiration, and surgery. Nonparametric statistical tests were used to compare the differences in the elastic parameters and BRAF genotypes between benign and malignant thyroid nodules of PTC, and receiver operating characteristic curve analysis was conducted to compare the diagnostic efficacy. In addition, the correlations between elastic parameters and BRAFV600E mutation in PTC were analyzed using binary logistic regression. The SWE, BRAFV600E, and their combination exhibited sensitivities of 72.9%, 81.3%, and 85.4%, respectively, and specificities of 66.7%, 90.3%, and 86.5%, respectively, in the diagnosis of PTC (P < 0.05). The SWE, BRAFV600E, and their combination exhibited sensitivities of 50.0%, 24.1% and 56.3%, respectively, and specificities of 89.7%, 87.5% and 82.8%, respectively, in the diagnosis of central cervical lymph node metastasis (P < 0.05). The combined use of SWE and BRAFV600E detection had the largest area under the curve, indicating that this combination is more effective in diagnosing PTC and lymph node metastasis in the central region than either method alone. Furthermore, Emax was positively associated with the BRAFV600E genotype. In conclusion, the combination of SWE and BRAFV600E genotype detection can improve the diagnostic efficacy for PTC. Emax can predict the BRAFV600E mutation status.
Ultrasound Attenuation Imaging vs MRI-PDFF, Echogenicity and Liver Function for Assessing Degree of Steatosis in NAFLD and Non-NAFLD Patients
Authors: Thomas Matthew , Dighe Manjiri , Kolokythas Orpheus , Zecevic Mladen , Wilson Ann , Erpelding Todd , Dubinsky Theodore J.
Published: August 2023

Nonalcoholic fatty liver disease (NAFLD) is a primary cause of parenchymal liver disease globally. There are currently several methods available to test the degree of steatosis in NAFLD patients, but all have drawbacks that limit their use.

The objective of this study is to determine if a new technique, ultrasound (US) attenuation imaging (ATI), correlates with magnetic resonance proton density fat fraction imaging and hepatic echogenicity as seen on gray scale US imaging.

Fifty-four patients were recruited at the University of Washington Medical Center from individuals who had already been scheduled for hepatic US or magnetic resonance imaging (MRI). All participants then underwent both hepatic MRI proton density fat fraction and US. Ultrasound images were then evaluated using ATI with 2 observers who individually determined relative grayscale echogenicity.

Analysis showed positive correlation between ATI- and MRI-determined fat percentage in the case group (Spearman correlation: 0.50; P = 0.015). Furthermore, participants with NAFLD tended to have a higher ATI than controls (median: 0.70 vs 0.54 dB/cm/MHz; P < 0.001).

This study demonstrates that US ATI combined with grayscale imaging is an effective way of assessing the degree of steatosis in patients with moderate to severe NAFLD.
Investigation of Childhood Pneumonia With Thoracic Ultrasound
Authors: Buz Yaşar Ayşenur , Tarhan Merve , Atalay Basak , Kabaalioğlu Adnan , Girit Saniye
Published: August 2023

Childhood pneumonia is a common entity, and chest x-rays are widely used as an initial diagnostic step. To avoid radiation exposure in the pediatric age group, we assessed whether the diagnostic accuracy of ultrasound (US) imaging is sufficient in the diagnosis. One hundred thirty-three children with pneumonia (72 girls/61 boys) were participated to study between 2019 and 2021. All participants had a chest x-ray. Radiologists who perform the US scans and interpret the x-rays were blinded to each other. A comparative analysis was also done to assess US findings on pneumonia for different age groups. We compare the diagnostic accuracy of US and x-rays by McNemar test and receiver operating characteristic curves. Intraclass correlation coefficient values were calculated for the assessment of interobserver agreement of x-ray evaluation. The participants’ ages ranged from 1 month to 17 years and 8 months with a median age of 24 months (Q1: 8 and Q3: 66 months). Hospital stay lengths were longer, consolidation depths were greater, and presence of air bronchogram or pleural effusion was more frequent in school-age children. The proportion of consolidation seen on chest x-ray and transthoracic US scan was significantly different (P < 0.001). The area under the curve was greater in the US than in the chest x-ray (area under the curve, 0.94 and 0.76 respectively). There was a good agreement between the 2 interpreters on chest x-ray assessment (κ = 0.661). The thoracic US can be used as a safe and efficient imaging tool in the diagnosis of pediatric pneumonia.
THE IMPACT OF THE MEDITERRANEAN DIET AND LIFESTYLE INTERVENTION ON LIPOPROTEIN SUB-CLASS PROFILES AMONG METABOLIC SYNDROME PATIENTS. FINDINGS OF A RANDOMIZED CONTROLLED TRIAL
Authors: Candás-Estébanez Beatriz , Fernández-Cidón Bárbara , Corbella Emili , Tebé Cristian , Fanlo-Maresma Marta , Esteve-Luque Virginia , Salas-Salvadó Jordi , Fitó Montse , Riera-Mestre Antoni , Ros Emilio , Pintó Xavier
Published: August 2023

Background

Metabolic syndrome (MetS) is associated with alterations of lipoprotein structure and function that can be characterized with advanced lipoprotein testing (ADLT). The effect of Mediterranean diet (MedDiet) and of body weight loss on the lipoprotein subclass profile has been scarcely studied. Within the PREDIMED-Plus randomized controlled trial, a sub-study conducted in one of its recruiting centers aimed to evaluate the effects on lipoproteins properties assessed by ADLT of an intensive weight loss program based on an energy-reduced MedDiet (er-MedDiet) and physical activity (PA) promotion (intervention group) compared with energy-unrestricted MedDiet recommendations (control group) on lipoprotein subclasses.

Methods

202 patients with MetS (n=107, Intervention; n=95, Control) were included in this study. Conventional lipid profile and ADLTs were performed at baseline, 6 months and one year. Linear mixed models were used to assess the effects of intervention on lipoprotein profiles.

Results

The er-MedDiet+PA led to a significant decrease of body mass index by 1.5 Kg/m2at 6 months and 1.4 Kg/m2at 12 months and a reduction of waist circumference by 2.9 cm at 6 months and 2.2 cm at 12 months; an increase of 0.1 mmol/L of HDL-C at 12 months, and decreased triglycerides (Tg) at 6 months; and decreased LDL-C and non-HDL-C at 12 months. ADLT showed a decrease of small dense-LDL-C (sdLDL-C), intermediate-density lipoprotein (IDL)-C, and HDL-Tg, and an increase of large LDL-particles (P). The er-MedDiet+PA model predicted significant reductions of Tg, sdLDL-C, VLDL-Tg and large VLDL-P in the intervention group.

Conclusions

In comparison with MedDiet (control group), er-MedDiet+PA (intervention group) decreased plasma triglyceride, and triglyceride content in HDL and VLDL particles, decreased sdLDL-C, and increased large LDL particles, indicating beneficial changes against cardiovascular disease.
Impact of the COVID-19 Pandemic on International Business Travel and Associated Health Issues: A Survey of Japanese Public Companies
Authors: Tsukada Yayoi Teteuou , Okamura Ritsuko , Yasutake Masahiro
Published: August 2023

Objectives

Compared to long-term expatriates, the health issues of short-term international business travellers are less clear. Particularly, there are no reports on the impact of the COVID-19 pandemic. We explored the changes in health challenges faced by Japanese international business travellers owing to the COVID-19 pandemic.

Design

Cross-sectional survey research using questionnaires

Setting

We surveyed 3,845 listed public companies in Japan in September 2021.

Participants

A total of 251 companies responded (response rate: 6.5%), of which 131 (52%) had foreign travel requirements for their business.

Primary and secondary outcome measures

The survey included questions regarding company size, business type, necessity for foreign travel, destination and number of trips, common health issues that arise, and the importance of business travel before and after the COVID-19 pandemic.

Results

Among the companies, 44% replied that they could not predict the number of foreign business trips after the pandemic. However, 64% of companies responded that business travel would continue to be important in the future. Before the COVID-19 pandemic, the most important health concerns faced by business travellers were illness during travel (42%), followed by the prevention of infectious diseases and lifestyle disease management. Post-pandemic, 48% of the responses were for infectious diseases, including COVID-19, followed by 40% for travel-related diseases, and 25% for lifestyle-related diseases.

Conclusions

Owing to global economic and social activities, business travel will continue to be necessary in the post-COVID-19 era. Comprehensive health management including prevention of infectious diseases is desirable for business travel.

Strengths and limitations of this study

This study provides valuable insights into the health problems of short-term expatriates, an area which has been left relatively unexplored compared to its long-term counterparts.

The potentially transformative effects of the COVID-19 pandemic on the health and well-being of expatriates are also considered.

This study will form a foundational document for reviewing the impact of the pandemic and establishing a healthcare system designed for business travellers in preparation for future pandemics.

The survey was exclusively conducted among Japanese firms, which restricts its scope and generalisability.

Because the survey was conducted from managers’ perspective, it did not provide an accurate assessment of the actual health status of business travellers.
Construction and validation of a predictive model of mortality of tuberculosis-destroyed lung patients requiring mechanical ventilation: A single-center retrospective case-control study
Authors: Cui Kunping , Mao Yi , Jiang Liangshuang , Zheng Yongli , Yang Lang , Yang Yixiang , Wu Guihui , Tang Shenjie
Published: August 2023

Background

The mortality rate for intensive care unit (ICU) tuberculosis-destroyed lung (TDL) patients requiring mechanical ventilation remains high.

Methods

We conducted a retrospective analysis of adult TDL patients requiring mechanical ventilation who were admitted to the ICU of a tertiary infectious disease hospital in Chengdu, Sichuan Province, China from January 2019 to March 2023. Univariate and multivariate COX regression analyses were conducted to determine independent patient prognostic risk factors that were used to construct a predictive model of patient mortality.

Results

For the 331 study subjects, the median age was 63.0 (50.0-71.0) years, 262 (79.2%) were males and the mortality rate was 48.64% (161/331). Training and validation data sets were obtained from 245 and 86 patients, respectively. Analysis of the training data set revealed that a body mass index (BMI) of<18.5kg/m2, blood urea nitrogen level of ≥7.14mmol/L and septic shock were independent risk factors for increased mortality of TDL patients requiring mechanical ventilation. These variables were then used to construct a risk-based model for predicting patient mortality. Area under the curve,sensitivity and specificity values obtained using the model for the training data set were 0.808, 79.17% and 68.80%, respectively, and corresponding values obtained using the validation data set were 0.876, 95.12% and 62.22%. respectively. Results of concurrent correction curve and decision curve analyses verified the model possessed high predictiveability.

Conclusions

This model may facilitate early identification and classification-based clinical management of TDL patients requiring mechanical ventilation who are at high risk of death.
Gender gap for accelerometry-based physical activity across different age groups in five Brazilian cohort studies
Authors: Ricardo Luiza I. C. , Wendt Andrea , Tornquist Debora , Gonçalves Helen , Wehrmeister Fernando , da Silva Bruna Gonçalves C. , Tovo-Rodrigues Luciana , Santos Iná , Barros Aluisio , Matijasevich Alicia , Hallal Pedro C. , Domingues Marlos , Ekelund Ulf , Bielemann Renata M. , Crohechemore-Silva Inácio
Published: August 2023

Objectives

This study aims to evaluate the gender inequalities in accelerometer-based physical activity (PA) across different age groups using data from five Pelotas (Brazil) cohorts.

Methods

The data comes from four birth cohort studies, covering all live births in the urban area of Pelotas for each respective year (1982, 1993, 2004, and 2015), and the ‘Como vai?’ cohort study focusing on 60 years and above. Raw accelerometry data were collected on the non-dominant wrist using GENEActive/Actigraph devices and processed with the GGIR package. Overall PA was calculated at ages 1, 2, 4, 6, 11, 15, 18, 23, 30, and 60+ years, while moderate-to-vigorous PA (MVPA) was calculated from six years onwards. Absolute (difference) and relative (ratio) gender inequalities were calculated and intersectionality between gender and wealth was also evaluated.

Results

The sample sizes per cohort ranged from 965 to 3462 participants. The mean absolute gender gap was 19.3 minutes (95%CI: 12.7; 25.9), with the widest gap at 18 years (32.9 minutes; 95%CI: 30.1; 35.7) for MVPA. The highest relative inequality was found in older adults (ratio 2.0; 95%CI 1.92 to 2.08). Our intersectionality results showed that the poorest men being the most active group, accumulating around 60 minutes more MVPA per day compared with the wealthiest women at age 18.

Conclusion

Men were more physically active than women in all ages evaluated. PA gender inequalities start at an early age and intensifies in transition periods of life. Relative inequalities were marked among older adults.

What is already known on this topic

Gender inequalities in physical activity have been reported globally, but most of the evidence is focused in adolescents and young adults. The literature lacks studies on children and older adults.

What this study adds

We present gender inequalities in accelerometer-based physical activity across several age groups, from 1 year olds to older adults.

How this study might affect research, practice or policy

Ou study provides a comprehensive description of gender inequalities, identifying key age groups for intervention.
Identifying proteomic risk factors for cancer using prospective and exome analyses: 1,463 circulating proteins and risk of 19 cancers in the UK Biobank
Authors: Papier Keren , Atkins Joshua R , Tong Tammy YN , Gaitskell Kezia , Desai Trishna , Ogamba Chibuzor F , Parsaeian Mahboubeh , Reeves Gillian K , Mills Ian G , Key Tim J , Smith-Byrne Karl , Travis Ruth C
Published: August 2023

Background

Proteins are essential for the development and progression of cancer and for the human body’s defense against tumor onset. The availability of a large panel of protein measurements and whole exome sequence data in the UK Biobank has enabled the simultaneous examination of plasma protein associations with risk across multiple cancer sites and their potential role in cancer etiology.

Methods

We investigated the associations of plasma proteins with incidence of 19 cancers and 9 cancer subsites in up to 44,645 middle-aged adults in the UK Biobank, who had measurements of 1,463 plasma proteins generated using Olink Explore Proximity Extension Assay in baseline blood samples (2006-2010). Using multivariable-adjusted Cox regression, we estimated the risk of each protein with each cancer overall and by time-to-diagnosis after correction for multiple-testing. Identified protein-cancer associations were further assessed in an analysis of cancer risk usingcis-pQTL and exome-wide protein genetic scores (exGS) in all UK Biobank participants (n=337,543).

Results

We identified 371 proteins associated with the risk of at least one incident cancer, represented by a total of 621 protein-cancer associations. These proteins were associated with cancers of the blood (201 proteins), liver (131), kidney (51), lung (28), esophagus (22), colorectum (15), stomach (8), breast (5), prostate (3), endometrium (3), ovary (2), bladder (1), head and neck (1), and brain (1). 100 of these 621 protein-cancer associations persisted for cases diagnosed more than seven years after blood draw. Of these 621 associations, there was further support fromcis-pQTL analyses for the etiological role of TNFRSF14 in risk of non-Hodgkin lymphoma (NHL), and from whole exome protein score (exGS) analyses for 28 other protein-cancer associations, including SRP14 and risk of leukemia. Proteins with directionally concordant evidence from long time-to-diagnosis analyses and from bothcis-pQTL and exGS analyses were SFTPA2 for lung cancer, TNFRSF1B and CD74 for NHL, and ADAM8 for leukemia.

Conclusions

For the first time using an integrated multi-omics and cross-cancer approach, we have comprehensively assessed the plasma proteome in relation to cancer risk and identified multiple novel etiological candidates. Differences in the levels of many circulating proteins were detectable more than seven years before cancer diagnosis; while some of these are likely to be markers of early cancer processes that may inform risk stratification, and/or risk factors, concordant evidence from genetic analyses suggests that some may have a role in cancer development.
Phylogenies increase power to detect highly transmissible viral genome variants
Authors: May Michael R , Rannala Bruce
Published: August 2023

As demonstrated by the SARS-CoV-2 pandemic, the emergence of novel viral strains with increased transmission rates poses a significant threat to global health. Viral genome sequences, combined with statistical models of sequence evolution, may provide a critical tool for early detection of these strains. Using a novel statistical model that links transmission rates to the entire viral genome sequence, we study the power of phylogenetic methods—using a phylogenetic tree relating viral samples—and count-based methods—using case-counts of variants over time—to detect increased transmission rates, and to identify causative mutations. We find that phylogenies in particular can detect novel variants very soon after their origin, and may facilitate the development of early detection systems for outbreak surveillance.
Vaccine effectiveness against hospitalisation and comparative odds of hospital admission and severe outcomes with BQ.1, CH.1.1. and XBB.1.5 in England
Authors: Kirsebom Freja C M , Harman Katie , Lunt Rachel J , Andrews Nick , Groves Natalie , Aziz Nurin Abdul , Hope Russell , Stowe Julia , Chand Meera , Ramsay Mary , Dabrera Gavin , Kall Meaghan , Lopez Bernal Jamie
Published: August 2023

Background

Since the first emergence of Omicron BA.1 in England in November 2021, numerous sub-lineages have evolved. In September 2022, BA.5 dominated. The prevalence of BQ.1 increased from October, while the prevalence of CH.1.1 and XBB.1.5 increased from December 2022 and January 2023, respectively. Little is known about the effectiveness of the vaccines against hospitalisation with these sub-lineages, nor the relative severity.

Methods

A test-negative case-control study was used to estimate the incremental effectiveness of the bivalent BA.1 booster vaccines against hospitalisation, relative to those with waned immunity where the last dose was at least 6 months prior. The odds of hospital admission for those testing PCR positive on the day of an attendance to accident and emergency departments and the odds of intensive care unit admission or death amongst COVID-19 admissions were compared between variants. Additionally, a Cox proportional hazards survival regression was used to investigate length of stay amongst hospitalised cases by variant.

Findings

There was no difference in incremental vaccine effectiveness against hospitalisation with BQ.1, CH.1.1 or XBB.1.5, nor was there a difference in the severity of these variants. Effectiveness against hospitalisation was 48.0% (95% C.I.; 38.5-56.0%), 29.7% (95% C.I.; 7.5-46.6%) and 52.7% (95% C.I.; 24.6-70.4%) against BQ.1, CH.1.1 and XBB.1.5, respectively, at 5 to 9 weeks post booster vaccination. Compared to BQ.1, the odds of hospital admission were 0.87 (95% C.I.; 0.77-0.99) and 0.88 (95% C.I.; 0.75-1.02) for CH.1.1 and XBB.1.5 cases attending accident and emergency departments, respectively. There was no significant difference in the odds of admission to intensive care units or death for those with CH.1.1 (OR 0.96, 95% C.I.; 0.71–1.30) or XBB.1.5 (OR 0.67, 95% C.I.; 0.44-1.02) compared to BQ.1. There was also no significant difference in the length of hospital stay by variant.

Interpretation

Together, these results provide reassuring evidence that the bivalent BA.1 booster vaccines provide similar protection against hospitalisation with BQ.1, CH.1.1 and XBB.1.5, and that the emergent CH.1.1 and XBB.1.5 sub-lineages do not cause more severe disease than BQ.1.

Funding

None.
Healthcare resource utilization and costs associated with COVID-19 among pediatrics managed in the community or hospital setting in England: a population-based cohort study
Authors: Yang Jingyan , Andersen Kathleen M. , Rai Kiran K. , Tritton Theo , Mugwagwa Tendai , Tsang Carmen , Reimbaeva Maya , McGrath Leah J. , Payne Poppy , Backhouse Bethany , Mendes Diana , Butfield Rebecca , Wood Robert , Nguyen Jennifer L.
Published: August 2023

Background

Although COVID-19 morbidity is significantly lower in pediatrics than in adults, the risk of severe COVID-19 may still pose substantial healthcare resource burden. This study aimed to describe healthcare resource utilization (HCRU) and costs associated with COVID-19 in pediatrics aged 1-17 years in England.

Methods

A population-based retrospective cohort study of pediatrics with COVID-19 using Clinical Practice Research Datalink (CPRD Aurum) primary care data and, where available, linked Hospital Episode Statistics Admitted Patient Care (HES APC) secondary care data. HCRU and associated costs to the National Health Service (NHS) were stratified by age, risk of severe COVID-19, and immunocompromized status, separately for those with and without hospitalization records (hospitalized cohort: COVID-19 diagnosis August 2020-March 2021; primary care cohort: COVID-19 diagnosis August 2020-January 2022).

Results

This study included 564,644 patients in the primary care cohort and 60 in the hospitalized cohort. Primary care consultations were more common in those aged 1-4 years (face-to-face: 4.3%; telephone: 6.0%) compared to those aged 5-11 (2.0%; 2.1%) and 12-17 years (2.2%; 2.5%). In the hospitalized cohort, mean [SD] length of stay was longer (5.0 [5.8] days) among those aged 12-17 years (n=24) than those aged 1-4 (n=15; 1.8 [0.9] days) and 5-11 years (n=21; 2.8 [2.1] days).

Conclusions

Most pediatrics diagnosed with COVID-19 were managed in the community. However, hospitalizations were an important driver of HCRU and costs, particularly for those aged 12-17 years. Our results may help optimize the management and resource allocation of COVID-19 in this population.
Validation of the LINEAR deflation algorithm of the Midmark IQvitals Zone Vital Signs Monitor: improving patient comfort from quicker BP acquisition
Authors: Alpert Bruce S.
Published: August 2023

Objectives

To assess the accuracy of the Midmark IQvitals®Zone™ wireless vital signs monitor LINEAR deflation algorithm to the requirements of the ANSI/AAMI/ISO 81060-2 Standard and the British Hypertension Society (BHS) Protocol.

Methods

The Standard and BHS testing each call for ≥ 85 subjects with requirements for gender, blood pressure (BP), and arm circumference. The testers performing auscultation were blinded. Statistical calculations as per requirements were performed.

Results

The mean ± SD for the 81060-2 Criterion 1 were 1.98 ± 6.90 mmHg for systolic and 0.54 ± 5.79 mmHg for diastolic BP. The Criterion 2 SD values were 5.60 mmHg for systolic and 5.26 mmHg for diastolic BP. All of these values passed the Standard requirements. The overall BHS rating was AA.

Conclusions

The Midmark LINEAR algorithm is validated based on the results. Use of the algorithm results in shorter cuff deflation times, thus improving patient comfort. The LINEAR algorithm has multiple features to improve BP measurement accuracy in critical patient populations.
Systematic Review and Meta-Analysis Protocol of the Efficacy and Safety of COVID-19 Drug Candidates Targeting Host Enzymes Involved in Immune Response
Authors: Mushebenge Aganze Gloire-Aimé , Ugbaja Samuel Chima , Mbatha Nonkululeko Avril , Riziki Manimani Ghislain , Muzumbukilwa Tambwe Willy , kadima Mukanda Gedeon , Kumalo Hezekiel M.
Published: August 2023

Introduction

COVID-19 is a rapidly spreading infectious disease caused by the SARS-CoV-2 virus. Although several therapeutic interventions have been developed, the mortality rate of the disease remains high, and effective treatment options are urgently needed. Host-directed therapies targeting enzymes involved in the immune response represent a promising strategy for the development of novel therapeutics against COVID-19. This study aims to conduct a systematic review and meta-analysis of the literature to evaluate the potential of drug candidates targeting host enzymes involved in the immune response for the treatment of COVID-19.

Methods and analysis

We will conduct a systematic search of electronic databases including PubMed, Embase, and Cochrane Library, as well as preprint servers and clinical trial registries for relevant studies. We will include randomized controlled trials, observational studies, and preclinical studies evaluating the efficacy of drug candidates targeting host enzymes involved in the immune response in COVID-19. Two reviewers will independently screen articles, extract data, and assess study quality. The primary outcome will be the effect of drug candidates on mortality, while secondary outcomes will include time to recovery, adverse events, and changes in immune markers. A meta-analysis will be performed to estimate pooled effect sizes of the interventions, and a narrative synthesis will be conducted for studies that are not amenable to quantitative analysis. This study will provide a comprehensive evaluation of the potential of host-directed therapies targeting enzymes involved in the immune response for the treatment of COVID-19. The results of this study may guide the development of novel therapeutics against COVID-19 and inform clinical practice.

Ethics and dissemination

This study will review published data, and thus it is unnecessary to obtain ethical approval. The findings of this systematic review will be published in a peer-reviewed journal.

PROSPERO registration number

CRD42023415110.
Assessing the role of rare pathogenic variants in heart failure progression by exome sequencing in 8,089 patients
Authors: Chazara Olympe , Dubé Marie-Pierre , Wang Quanli , Middleton Lawrence , Vitsios Dimitrios , Walentinsson Anna , Wang Qing-Dong , Hansson Kenny M. , Granger Christopher B. , Kjekshus John , Haefliger Carolina , Tardif Jean-Claude , Paul Dirk S. , Carss Keren
Published: August 2023

Most therapeutic development is targeted at slowing disease progression, often long after the initiating events of disease incidence. Heart failure is a chronic, life-threatening disease and the most common reason for hospital admission in people over 65 years of age. Genetic factors that influence heart failure progression have not yet been identified. We performed an exome-wide association study in 8,089 patients with heart failure across two clinical trials, CHARM and CORONA, and one population-based cohort, the UK Biobank. We assessed the genetic determinants of the outcomes ‘time to cardiovascular death’ and ‘time to cardiovascular death and/or hospitalisation’, identifying seven independent exome-wide-significant associated genes,FAM221A,CUTC,IFIT5,STIMATE,TAS2R20,CALB2andBLK. Leveraging public genomic data resources, transcriptomic and pathway analyses, as well as a machine-learning approach, we annotated and prioritised the identified genes for further target validation experiments. Together, these findings advance our understanding of the molecular underpinnings of heart failure progression and reveal putative new candidate therapeutic targets.
Ezetimibe and Atherosclerotic Cardiovascular Disease: A Systematic Review and Meta-Analyses
Authors: Omidi Fatemeh , Rahmannia Maryam , Mohammadsharifi Parsa , Nasiri Mohammad Javad , Sarmastzadeh Tala
Published: August 2023

Introduction

Individuals diagnosed with atherosclerotic cardiovascular disease (ASCVD), particularly those who have experienced acute coronary syndrome (ACS) within the past year, are at a heightened risk of recurrent cardiovascular events. Lowering low-density lipoprotein cholesterol (LDL-C) levels has been proven effective in reducing this risk. However, there is a lack of a comprehensive meta-analysis investigating the LDL-C-lowering effectiveness and coronary atherosclerotic plaque compositions of Ezetimibe. This study aims to address this gap in knowledge.

Methods

We conducted a systematic review of randomized controlled trials that evaluated the LDL-C-lowering efficacy and coronary atherosclerotic plaques efficacy of ezetimibe in patients with ASCVD. We searched relevant databases, including MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials, for publications from database inception until Jul 2023. Meta-analyses were performed to assess the LDL-C-lowering and coronary atherosclerotic plaques efficacy of ezetimibe in the overall ASCVD population.

Results

The meta-analysis included a total of 20 eligible studies. Our findings revealed that combination therapy of ezetimibe with statins resulted in a more substantial absolute reduction in LDL-C compared to statin monotherapy (mean difference of (−14.06 mg/dL; 95% confidence interval [CI] −18.0 to −10.0; p = 0.0001) after 6-12 months of treatment (or at a time point nearest to 6 -12months). Moreover, the subgroups analysis indicates that the intervention measures were effective in reducing the volume of fibro-fatty plaque (FFP) when compared to the control group [weighted mean difference (WMD) = -1.01, 95% confidence interval (CI) (-3.6 and 1.6), and p = 0.003], necrotic core (NC) volume [WMD =-5.41, 95% CI(-13.3 and 2.5), and p = 0.35], and change dense calcification (change DC) volume [WMD =-1.14, 95% CI (- 1.4 and – 0.8), and p = 0.62] between the treatment group and the control group.

Conclusions

Our study indicates that the addition of ezetimibe to statin therapy results in a modest yet significant further reduction in LDL-C compared to statin monotherapy. Ezetimibe led to a significant reduction in FFP volume; however, there were no statistically significant differences observed for NC, or change DC volumes.
Qualitative description of interpersonal HIV stigma and motivations for HIV testing among gays, bisexuals, and men who have sex with men in Ghana’s slums - BSGH-005
Authors: Abu-Ba’are Gamji Rabiu , Zigah Edem Yaw , Shamrock Osman Wumpini , Ogunbajo Adedotun , Dakpui Henry Delali , Agbemedu George Rudolph Kofi , Boyd Donte , Ezechie Oliver , Nelson LaRon , Torpey Kwasi
Published: August 2023

Despite significant progress in Ghana’s HIV response, disparities in HIV prevalence persist among different populations. Gays, bisexuals, and other men who have sex with men (GBMSM) in the country remain vulnerable to HIV infection due to high levels of stigma and discrimination, limited access to healthcare services, and low HIV knowledge levels. While limited studies focus on HIV prevention and care in the Ghanaian GBMSM context, we did not find studies on GBMSM in slums. We, therefore, explored stigma and motivations of HIV testing among GBMSM in slums. In collaboration with our community partners, we recruited and conducted face-to-face interviews among 12 GBMSM from slums in Accra and Kumasi, Ghana. Our multiple-reviewer summative content analysis identified the following: under HIV stigma, we identified two categories, avoidance of GBMSM living with HIV and fear of testing positive for HIV. Under motivations for HIV testing, we identified three categories; HIV vulnerability, sexual health decision making, and positive messaging about HIV. Our findings provide valuable insights into stigma and motivations for HIV testing among GBMSM in Ghanaian slums. They also highlight the importance of targeted HIV education interventions to empower GBMSM to take responsibility for their sexual health and address the unique challenges they face accessing HIV testing services.
SARS-CoV-2 live virus culture and sample freeze-thaw stability
Authors: Kanki Phyllis J. , Hamel Donald J. , Riedel Stefan , Dutta Sanjucta , Cheng Annie , Chang Charlotte A. , Arnaout Ramy , Kirby James E.
Published: August 2023

The COVID-19 pandemic has presented unique diagnostic challenges including the need to store and test large number of samples for clinical and research studies. While SARS CoV-2 diagnosis relies on RT-qPCR and antigen testing, live virus culture remains an important surrogate for viral “infectiousness”, as we previously described in “SARS-CoV-2 Antigen Tests Predict Infectivity Based on Viral Culture: Comparison of Antigen, PCR Viral Load and Viral Culture Testing on a Large Sample Cohort” (Clin Microbiol Infect, 2022,PMC9293398). Live virus isolation and characterization has also been important to the SARS CoV-2 research community, to assess viral fitness, cellular tropism, and live virus neutralization, particularly with the emergence of new variants. Many clinical and research studies make use of samples that are frozen in transport media and investigated at later dates. The effect of freezing on RT-qPCR results is well established. However, the effect of freeze-thaw on viral viability has not been. Here, we therefore examined the effect of freeze-thaw on viral culture isolation from a large number of clinical samples that were split, and then cultured either fresh or after being frozen for 7 or 17-18 days. Samples represented the range of viral loads (genome copies/mL) observed in our patient population. We found that freeze-thaw did not significantly affect viral culture isolation. Therefore, the ability to assess infectiousness of samples previously frozen in transport medium appears to be maintained.
An example of too much too soon? A retrospective review of Caesarean Sections performed in the first stage of labour in Kenya
Authors: Allott Helen , Dickinson Fiona , Karangau Stephen , Oduor Michael , Shaaban Nassir , Ogoti Evans , Sawe Sheila , Ochola Ephraim , Ameh Charles
Published: August 2023

Objective

In Kenya, decisions to perform CS are frequently made by unsupported non-specialist doctors, sometimes resulting in sub-optimal decision-making and inappropriate surgery. This study assesses decision-making in CS performed in the first stage of labour by a retrospective case review.

Methods

A panel of expert obstetricians reviewed case-notes randomly selected from a series obtained from seven Kenyan referral hospitals, then discussed in pairs and as a group where opinions differed.

Results

Of the 87 case-notes reviewed consensus was achieved in 94.3% cases. In 41.3% cases, CS was considered appropriate by all assessors, including 8.9% cases where the CS was necessary but performed too late. The decision to delivery interval was 2 hours or longer in 65.8% cases, including 18 cases done for non-reassuring fetal status. In 10.3% it was considered that further reassessment should have occurred.

In 9.2% the reviewers concluded that the CS was done too soon and alternative measures could have been taken. Insufficient information was available in the records to make a full assessment in 21.8% of cases and in 11.5% the CS was considered to be inappropriate.

Conclusions

This review suggests a need for improved support for decision-making, improved record-keeping and more timely surgery when indicated.

Synopsis

At least 11.5% of Caesarean Sections in the first stage of labour could be avoided if decision-makers had access to support from more experienced practitioners.
Detection of autoantibodies against the acetylcholine receptor, evaluation of commercially available methodologies: fixed Cell-Based Assay, Radioimmunoprecipitation Assay and Enzyme-Linked Immunosorbent Assay
Authors: Diogenes Larissa , Dellavance Alessandra , Baldo Danielle Cristiane , Gozzi-Silva Sarah Cristina , Gomes Kethellen , Prado Monica Simon , Andrade Luis Eduardo C. , Keppeke Gerson Dierley
Published: August 2023

Introduction

Myasthenia Gravis (MG) is an autoimmune disease resulting from the action of pathogenic autoantibodies (AAbs) directed against nicotinic acetylcholine receptors (AChR), which interfere with communication between the neurotransmitter acetylcholine and its receptor on the muscle fiber. The detection of anti-AChR using Radio Immuno Precipitation Assay (RIPA) has 100% specificity for the diagnosis of MG, however RIPA has high execution and interpretation complexity and requires radioactive materials, which restrict their use to specialized laboratories.

Objective

We compared the performance of the gold standard RIPA with different non-RIPA anti-AChR immunoassays, including a cell-based assay (CBA) and two solid-phase ELISA kits.

Results

145 samples were included with medical indication for anti-AChR testing. By the RIPA method, 63 were negative (RIPA-Neg <0.02 nmol/L), 17 were classified as Borderline(≥0.02 – 1 nmol/L), and 65 were positive (RIPA-Pos >1 nmol/L). The competitive ELISA yielded a poor performance with low Kappa agreement with RIPA (0.210). The indirect ELISA yielded a substantial Kappa agreement (Kappa=0.652), with ∼70% sensitivity and ∼96% specificity, compared to RIPA. In a semiquantitative analysis, there was a good Spearman correlation between the indirect ELISA and RIPA levels (r=0.845). The best performance was observed with the CBA that uses fixed cells expressing clustered AChR as antigenic substrate. There was an almost perfect agreement with RIPA (Kappa = 0.969), with ∼97% sensitivity and 100% specificity. However, in theBorderlinegroup, only 5 (∼30%) were positive using the CBA method, suggesting a slightly lower sensitivity for the CBA.

Conclusion

For detection of anti-AChR reactivity, the indirect immunofluorescence assay yielded a very good analytical performance taking RIPA as the reference method, with potential to replace the RIPA in the clinical laboratory. ELISA could be an option to estimate anti-AChR AAb levels after confirming positivity by the CBA.
Flexible and Highly-Efficient Feature Perception for Molecular Traits Prediction via Self-interactive Deep Learning
Authors: Hu Yang , Sirinukunwattana Korsuk , Li Bin , Gaitskell Kezia , Bonnaffé Willem , Wojciechowska Marta , Wood Ruby , Alham Nasullah Khalid , Malacrino Stefano , Woodcock Dan , Verrill Clare , Ahmed Ahmed , Rittscher Jens
Published: August 2023

Predicting disease-related molecular traits from histomorphology brings great opportunities for precision medicine. Despite the rich information present in histopathological images, extracting fine-grained molecular features from standard whole slide images (WSI) is non-trivial. The task is further complicated by the lack of annotations for subtyping and contextual histomorphological features that might span multiple scales. This work proposes a novel multiple-instance learning (MIL) framework capable of WSI-based cancer morpho-molecular subtyping across scales. Our method, debuting as Inter-MIL, follows a weakly-supervised scheme. It enables the training of the patch-level encoder for WSI in a task-aware optimisation procedure, a step normally improbable in most existing MIL-based WSI analysis frameworks. We demonstrate that optimising the patch-level encoder is crucial to achieving high-quality fine-grained and tissue-level subtyping results and offers a significant improvement over task-agnostic encoders. Our approach deploys a pseudo-label propagation strategy to update the patch encoder iteratively, allowing discriminative subtype features to be learned. This mechanism also empowers extracting fine-grained attention within image tiles (the small patches), a task largely ignored in most existing weakly supervised-based frameworks. With Inter-MIL, we carried out four challenging cancer molecular subtyping tasks in the context of ovarian, colorectal, lung, and breast cancer. Extensive evaluation results show that Inter-MIL is a robust framework for cancer morpho-molecular subtyping with superior performance compared to several recently proposed methods, even in data-limited scenarios where the number of available training slides is less than 100. The iterative optimisation mechanism of Inter-MIL significantly improves the quality of the image features learned by the patch embedded and generally directs the attention map to areas that better align with experts’ interpretation, leading to the identification of more reliable histopathology biomarkers.
Semi-Quantitative Group Testing for Efficient and Accurate qPCR Screening of Pathogens with a Wide Range of Loads
Authors: Nambiar Ananthan , Pan Chao , Rana Vishal , Cheraghchi Mahdi , Ribeiro João , Maslov Sergei , Milenkovic Olgica
Published: August 2023

Pathogenic infections pose a significant threat to global health, affecting millions of people every year and presenting substantial challenges to healthcare systems worldwide. Efficient and timely testing plays a critical role in disease control and transmission prevention. Group testing is a well-established method for reducing the number of tests needed to screen large populations when the disease prevalence is low. However, it does not fully utilize the quantitative information provided by qPCR methods, nor is it able to accommodate a wide range of pathogen loads. To address these issues, we introduce a novel adaptive semi-quantitative group testing (SQGT) scheme to efficiently screen populations via two-stage qPCR testing. The SQGT method quantizes cycle threshold (Ct) values into multiple bins, leveraging the information from the first stage of screening to improve the detection sensitivity. DynamicCtthreshold adjustments mitigate dilution effects and enhance test accuracy. Comparisons with traditional binary outcome GT methods show that SQGT reduces the number of tests by 24% while maintaining a negligible false negative rate.