bluuebunny/crossref_metadata_2025 huggingface dataset:
Predictors and Effects of Participation in Peer Support: A Prospective Structural Equation Modeling Analysis
Authors: Ayala Guadalupe Xochitl , Chan Juliana C N , Cherrington Andrea L , Elder John , Fisher Edwin B , Heisler Michele , Howard Annie Green , Ibarra Leticia , Parada Humberto , Safford Monika , Simmons David , Tang Tricia S
Published: July 2022

Background

Peer support provides varied health benefits, but how it achieves these benefits is not well understood.

Purpose

Examine a) predictors of participation in peer support interventions for diabetes management, and b) relationship between participation and glycemic control.

Methods

Seven peer support interventions funded through Peers for Progress provided pre/post data on 1,746 participants’ glycemic control (hemoglobin A1c), contacts with peer supporters as an indicator of participation, health literacy, availability/satisfaction with support for diabetes management from family and clinical team, quality of life (EQ-Index), diabetes distress, depression (PHQ-8), BMI, gender, age, education, and years with diabetes.

Results

Structural equation modeling indicated a) lower levels of available support for diabetes management, higher depression scores, and older age predicted more contacts with peer supporters, and b) more contacts predicted lower levels of final HbA1c as did lower baseline levels of BMI and diabetes distress and fewer years living with diabetes. Parallel effects of contacts on HbA1c, although not statistically significant, were observed among those with baseline HbA1c values > 7.5% or > 9%. Additionally, no, low, moderate, and high contacts showed a significant linear, dose–response relationship with final HbA1c. Baseline and covariate-adjusted, final HbA1c was 8.18% versus 7.86% for those with no versus high contacts.

Conclusions

Peer support reached/benefitted those at greater disadvantage. Less social support for dealing with diabetes and higher PHQ-8 scores predicted greater participation in peer support. Participation in turn predicted lower HbA1c across levels of baseline HbA1c, and in a dose–response relationship across levels of participation.
Dynamics of microbiota in the imported beef primal cuts during storage at different chilled temperatures
Authors: Nakamura Ayaka , Mizuno Yuri , Takahashi Hajime , Otomo Kota , Kuda Takashi , Kimura Bon
Published: July 2022

Primal cuts of Australian beef transported by sea were stored under different chilled temperatures (0, 2, and 4 °C) for 6 weeks in different packaging conditions (aerobic or anaerobic packaging). The number of microorganisms and the transition of the microbiota were investigated using culture methods and amplicon sequencing. After 6 weeks of storage, the beef tended to show a high total viable count under aerobic packaging conditions and a high lactic acid bacteria count under anaerobic packaging conditions. The result of amplicon sequencing analysis showed that different beef samples had different predominant bacterial groups. Moreover, at high storage temperatures, Serratia sp. having high putrefactive activity showed increased abundance, while at low storage temperatures, Lactobacillus sp. showed increased abundance. Thus, differences in the packaging conditions and distribution temperatures after import affect the number of bacteria and the type of microorganisms in the Australian beef primal cuts, which may affect their quality.
Association of PCOS with offspring morbidity: a longitudinal cohort study
Authors: Wei Shu Qin , Bilodeau-Bertrand Marianne , Auger Nathalie
Published: July 2022

STUDY QUESTION

Do children whose mothers have polycystic ovary syndrome (PCOS) have an increased risk of morbidity?

SUMMARY ANSWER

Maternal PCOS is associated with an increased risk of infection, allergy and other childhood morbidity.

WHAT IS KNOWN ALREADY

PCOS is associated with higher rates of gestational diabetes, pre-eclampsia and preterm delivery, but the long-term impact on child health is poorly understood.

STUDY DESIGN, SIZE, DURATION

We conducted a retrospective longitudinal cohort study of 1 038 375 children in Quebec between 2006 and 2020.

PARTICIPANTS/MATERIALS, SETTING, METHODS

We included 7160 children whose mothers had PCOS and 1 031 215 unexposed children. Outcomes included child hospitalization for infectious, allergic, malignant and other diseases before 13 years of age. We estimated hazard ratios (HRs) and 95% CI for the association of PCOS with childhood morbidity in adjusted Cox proportional hazards regression models.

MAIN RESULTS AND THE ROLE OF CHANCE

Children exposed to PCOS were hospitalized at a rate of 68.9 (95% CI 66.2–71.8) per 1000 person-years, whereas unexposed children were hospitalized at a rate of 45.3 (95% CI 45.1–45.5) per 1000 person-years. Compared with no exposure, maternal PCOS was associated with 1.32 times the risk of any childhood hospitalization (95% CI 1.26–1.40), 1.31 times the risk of infectious disease hospitalization (95% CI 1.25–1.38) and 1.47 times the risk of allergy-related hospitalization (95% CI 1.31–1.66). Risk of hospitalization was also elevated for childhood metabolic (HR 1.59, 95% CI 1.16–2.18), gastrointestinal (HR 1.72, 95% CI 1.53–1.92), central nervous system (HR 1.74, 95% CI 1.46–2.07) and otologic disorders (HR 1.34, 95% CI 1.26–1.43). Subgroup analyses suggested that there was little difference in the association of PCOS with hospitalization among boys (HR 1.31, 95% CI 1.24–1.39) and girls (HR 1.34, 95% CI 1.26–1.43).

LIMITATIONS, REASONS FOR CAUTION

We analyzed severe childhood morbidity requiring hospitalization, not mild diseases treated in ambulatory clinics. We lacked data on ethnicity, education and physical activity, and cannot rule out residual confounding.

WIDER IMPLICATIONS OF THE FINDINGS

Our findings suggest that maternal PCOS is associated with an increased risk of childhood morbidity.

STUDY FUNDING/COMPETING INTEREST(S)

This study was supported by grant PJT-162300 from the Canadian Institutes of Health Research. N.A. acknowledges a career award from the Fonds de recherche du Québec-Santé (296785). The authors declare no competing interests.

TRIAL REGISTRATION NUMBER

N/A.
Heterogeneous effects and spillovers of macroprudential policy in an agent-based model of the UK housing market
Authors: Carro Adrian , Hinterschweiger Marc , Uluc Arzu , Farmer J Doyne
Published: July 2022

We develop an agent-based model of the UK housing market to study the impact of macroprudential policy experiments on key housing market indicators. The heterogeneous nature of this model enables us to assess the effects of such experiments on the housing, rental, and mortgage markets not only in the aggregate, but also at the level of individual households and sub-segments, such as first-time buyers, homeowners, buy-to-let (BTL) investors, and renters. This approach can, therefore, offer a broad picture of the disaggregated effects of financial stability policies. The model is calibrated using a large selection of micro-data, including data from a leading UK real-estate online search engine as well as loan-level regulatory data. With a series of comparative static exercises, we investigate the impact of (i) a hard loan-to-value limit and (ii) a soft loan-to-income limit, allowing for a limited share of unconstrained new mortgages. We find that, first, these experiments tend to mitigate the house price cycle by reducing credit availability and therefore leverage. Second, an experiment targeting a specific risk measure may also affect other risk metrics, thus necessitating a careful calibration of the policy to achieve a given reduction in risk. Third, experiments targeting the owner-occupier housing market can spill over to the rental sector, as a compositional shift in home ownership from owner-occupiers to BTL investors affects both the supply of and the demand for rental properties.
Population pharmacokinetic study of benzathine penicillin G administration in Indigenous children and young adults with rheumatic heart disease in the Northern Territory, Australia
Authors: Kado Joseph , Salman Sam , Hand Robert , O’Brien Margaret , Ralph Anna , Bowen Asha C , Page-Sharp Madhu , Batty Kevin T , Dolman Veronica , Francis Joshua R , Carapetis Jonathan , Manning Laurens
Published: July 2022

Background

Benzathine penicillin G (BPG) is the cornerstone of secondary prophylaxis to prevent Streptococcus pyogenes infections, which precede acute rheumatic fever (ARF). The paucity of pharmacokinetic (PK) data from children and adolescents from populations at the highest risk of ARF and rheumatic heart disease (RHD) poses a challenge for determining the optimal dosing and frequency of injections and undermines efforts to develop improved regimens.

Methods

We conducted a 6 month longitudinal PK study of young people receiving BPG for secondary prophylaxis. Throat and skin swabs were collected for microbiological culture along with dried blood spot (DBS) samples for penicillin concentrations. DBSs were assayed using LC-MS/MS. Penicillin concentration datasets were analysed using non-linear mixed-effects modelling and simulations performed using published BMI-for-age and weight-for-age data.

Results

Nineteen participants provided 75 throat swabs, 3 skin swabs and 216 penicillin samples. Throat cultures grew group C and G Streptococcus. Despite no participant maintaining penicillin concentration >20 ng/mL between doses, there were no S. pyogenes throat infections and no ARF. The median (range) observed durations >20 ng/mL for the low- and high-BMI groups were 14.5 (11.0–24.25) and 15.0 (7.5–18.25) days, respectively.

Conclusions

Few patients at highest risk of ARF/RHD receiving BPG for secondary prophylaxis maintain penicillin concentrations above the target of 20 ng/mL beyond 2 weeks during each monthly dosing interval. These PK data suggest that some high-risk individuals may get inadequate protection from every 4 week dosing. Future research should explore this gap in knowledge and PK differences between different populations to inform future dosing schedules.
An ethico-legal assessment of intellectual property rights and their effect on COVID-19 vaccine distribution: an Australian case study
Authors: Scheibner James , Nielsen Jane , Nicol Dianne
Published: July 2022

This article posits that Australia, as an affluent country with increasing capacity to manufacture vaccines, has an obligation to assist its regional (and global) counterparts in implementing vaccination programs that protect their populations. First, the article explores the capacity of high-income nations to meet their obligations, assist their neighbours and refrain from vaccine nationalism. This inquiry involves an analysis of the optimal ethical strategy for distributing vaccines globally, and the role that Australia might play in this distribution strategy. Secondly, the article examines the intellectual property landscape for vaccines in Australia, focusing on the patents that cover vaccine compositions and manufacturing techniques (recognizing the potential for know-how and access to materials as well as patents to affect manufacturing capacity). This article then discusses the strategies the Australian Government has at its disposal to counter potential intellectual property impediments whilst complying with existing obligations under the Agreement on Trade-related Aspects of Intellectual Property Rights (TRIPS), as an ethically appropriate response to the pandemic. This article also considers whether a so-called TRIPS waiver could provide better options and concludes that the challenge of compelling disclosure of know-how remains.
Diver Underwater Cycling Endurance After Short-Term Warm and Hot Water Acclimation
Authors: Wheelock Courtney E , Looney David P , Potter Adam W , Pryor Riana R , Pryor J Luke , Florian John , Hostler David
Published: July 2022

Introduction

It is unclear whether immersion heat acclimation benefits exercise in warm water conditions. This study examined the effects of heat acclimation strategies on heart rate (HR), core temperature, and time to exhaustion (TTE) during cycling exercise in varying warm water conditions.

Methods

Twenty male divers completed this study at the Navy Experimental Diving Unit. Subjects were randomly assigned to one of two 9-day heat acclimation groups. The first group (WARM; n = 10) cycled for 2 hours at 50 W in 34.4 °C water, while the second group (HOT; n = 10) cycled for 1 hour against minimal resistance in 36.7 °C water. Following acclimation, TTE was tested by underwater cycling (30 W) in 35.8 °C, 37.2 °C, and 38.6 °C water.

Results

Throughout acclimation, the rate of core temperature rise in the first 30 minutes of exercise increased (P = .02), but the maximum core temperature reached was not different for either group. Time to exhaustion (TTE) was reduced, and the rate of core temperature rise during performance testing increased (both P < .001) with increasing water temperature but was not different between groups. Core temperature and HR increased throughout performance testing in each water condition and were lower in the HOT compared to the WARM acclimation group (all P < .05) with the exception of core temperature in the 37.2 °C condition.

Conclusions

Underwater exercise performance did not differ between the two acclimation strategies. This study suggests that passive acclimation to a higher water temperature may improve thermoregulatory and cardiovascular responses to exercise in warm water. Hot water immersion adaptations are dependent on exercise intensity and water temperature.
Enhancement of CRISPR/Cas12a trans-cleavage activity using hairpin DNA reporters
Authors: Rossetti Marianna , Merlo Rosa , Bagheri Neda , Moscone Danila , Valenti Anna , Saha Aakash , Arantes Pablo R , Ippodrino Rudy , Ricci Francesco , Treglia Ida , Delibato Elisabetta , van der Oost John , Palermo Giulia , Perugino Giuseppe , Porchetta Alessandro
Published: July 2022

The RNA programmed non-specific (trans) nuclease activity of CRISPR-Cas Type V and VI systems has opened a new era in the field of nucleic acid-based detection. Here, we report on the enhancement of trans-cleavage activity of Cas12a enzymes using hairpin DNA sequences as FRET-based reporters. We discover faster rate of trans-cleavage activity of Cas12a due to its improved affinity (Km) for hairpin DNA structures, and provide mechanistic insights of our findings through Molecular Dynamics simulations. Using hairpin DNA probes we significantly enhance FRET-based signal transduction compared to the widely used linear single stranded DNA reporters. Our signal transduction enables faster detection of clinically relevant double stranded DNA targets with improved sensitivity and specificity either in the presence or in the absence of an upstream pre-amplification step.
The Topography of Subnational Inequality
Authors: VanHeuvelen Tom
Published: July 2022

In this study, I examine inequality divergence, or the inequality of inequalities across local labor markets. While divergence trends of central tendencies such as per capita income have been well documented, less is known about the descriptive trends or contributing mechanisms for inequality itself. In this study, I construct wage inequality measures in 722 commuting zones covering the entire contiguous United States across 22 waves of Census and American Community Survey data from 1940 to 2019 to assess the historical trends of inequality divergence. I synthesize counterfactual and variance decomposition techniques to develop main conclusions. Results show two eras, one of convergence between 1950 and 1990, and divergence between 1990 and 2019, resulting in rates of divergence today as high as any time in the past 80 years. With a brief exception from 1990 to 2007, most changes occurred through the geographical mobility of wages across labor markets. In the 1950–1990 period, this primarily occurred through equalization of wages across regions and within the US South, while the takeoff of highly urban and unequal labor markets made a novel contribution to the 1990–2019 era. In total, results point to the fundamental importance of what I term the topography of inequality, or the contours of inequality levels across spatial locations and the change in the size and location of peaks and valleys across time, for understanding the full nature of long run inequality change.
Cancer mortality and predictions for 2022 in selected Australasian countries, Russia, and Ukraine with a focus on colorectal cancer
Authors: Pizzato Margherita , La Vecchia Carlo , Malvezzi Matteo , Levi Fabio , Boffetta Paolo , Negri Eva , Dalmartello Michela
Published: July 2022

Objective

We aimed at predicting cancer mortality rates for the current year for the Russian Federation, Ukraine, Israel, Hong Kong SAR, Japan, Korea, and Australia, with a focus on colorectal cancer.

Methods

We retrieved official death certification and population data from the WHO and the United Nations Population Division databases. We analyzed mortality for all cancers combined and for 10 major cancer sites from 1970 to 2019, or the latest available year. We predicted numbers of deaths and age-standardized mortality rates for 2022 using Poisson joinpoint regression models. We estimated the number of averted deaths over the period 1994–2022 because of the decline in mortality rates.

Results

Total cancer mortality declined in all countries and both sexes. Russia had the highest total cancer predicted rates for 2022: 156.4/100 000 (world standard) in men and 81.4 in women; the lowest rates were reported in Israeli men (90.6/100 000) and Korean women (44.5/100 000). Between 1994 and 2022, a total of 1 487 000 deaths were estimated to be avoided in Russia, 502 000 in Ukraine, 58 000 in Israel, 102 000 in Hong Kong SAR, 1 020 000 in Japan, 533 000 in the Republic of Korea, and 263 000 in Australia. Colorectal cancer mortality trends were downward for the last decades with favorable predictions for 2022 in both sexes.

Conclusion

In the countries considered, predicted downward trends started later and were less marked than those in the European Union and the USA. Despite overall favorable predictions, colorectal cancer remains one of the major causes of cancer mortality.
A trial of arbidol hydrochloride in adults with COVID-19
Authors: Zhao Jingya , Zhang Jinnong , Jin Yang , Tang Zhouping , Hu Ke , Sun Hui , Shi Mengmeng , Yang Qingyuan , Gu Peiyu , Guo Hongrong , Li Qi , Zhang Haiying , Li Chenghong , Yang Ming , Xiong Nian , Dong Xuan , Xu Juanjuan , Lin Fan , Wang Tao , Yang Chao , Huang Bo , Zhang Jingyi , Chen Shi , He Qiong , Zhou Min , Qu Jieming
Published: July 2022

Background:

To date, there is no effective medicine to treat coronavirus disease 2019 (COVID-19), and the antiviral efficacy of arbidol in the treatment for COVID-19 remained equivocal and controversial. The purpose of this study was to evaluate the efficacy and safety of arbidol tablets in the treatment of COVID-19.

Methods:

This was a prospective, open-label, controlled and multicenter investigator-initiated trial involving adult patients with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Patients were stratified 1:2 to either standard-of-care (SOC) or SOC plus arbidol tablets (oral administration of 200 mg per time, three times a day for 14 days). The primary endpoint was negative conversion of SARS-CoV-2 within the first week. The rates and 95% confidential intervals were calculated for each variable.

Results:

A total of 99 patients with laboratory-confirmed SARS-CoV-2 infection were enrolled; 66 were assigned to the SOC plus arbidol tablets group, and 33 to the SOC group. The negative conversion rate of SARS-CoV-2 within the first week in patients receiving arbidol tablets was significantly higher than that of the SOC group (70.3% [45/64] vs. 42.4% [14/33]; difference of conversion rate 27.9%; 95% confidence interval [CI], 7.7%–48.1%; P 
= 0.008). Compared to those in the SOC group, patients receiving arbidol tablets had a shorter duration of clinical recovery (median 7.0 days vs. 12.0 days; hazard ratio [HR]: 1.877, 95% CI: 1.151–3.060, P = 0.006), symptom of fever (median 3.0 days vs. 12.0 days; HR: 18.990, 95% CI: 5.350–67.410, P < 0.001), as well as hospitalization (median 12.5 days vs. 20.0 days; P < 0.001). Moreover, the addition of arbidol tablets to SOC led to more rapid normalization of declined blood lymphocytes (median 10.0 days vs. 14.5 days; P > 0.05). The most common adverse event in the arbidol tablets group was the elevation of transaminase (5/200, 2.5%), and no one withdrew from the study due to adverse events or disease progression.

Conclusions:

SOC plus arbidol tablets significantly increase the negative conversion rate of SARS-CoV-2 within the first week and accelerate the recovery of COVID-19 patients. During the treatment with arbidol tablets, we find no significant serious adverse events.

Trial registration:

Chinese Clinical Trial Registry, NCT04260594, www.clinicaltrials.gov/ct2/show/NCT04260594?term=NCT04260594&draw=2&rank=1
Associations of toluidine red unheated serum test response to the treatment of syphilis in pregnancy and congenital syphilis: a 10-year real-world study
Authors: Wei Jin , Pang Mengyao , Lun Wenhui
Published: July 2022

Background:

So far, there is a paucity of real-world data on the syphilis serological responses to the first-line treatment during pregnancy, and there is no relevant study on the necessity of anti-syphilis treatment during pregnancy for those patients who have been treated for syphilis before pregnancy for the prevention of mother-to-child transmission, which might provide valuable insight into treatment effectiveness and optimal management of pregnant women with syphilis.

Methods:

A retrospective study on 10 years of real-world data was performed for accumulative 410 Chinese pregnant women with syphilis. The descriptive statistics were conducted in the study, and toluidine red unheated serum test (TRUST) titer responses to penicillin treatment in syphilis-infected pregnant women, and the associations with congenital syphilis were investigated. We divided the patients into two groups according to the history of anti-syphilis treatment before pregnancy (patients diagnosed with syphilis who had received anti-syphilis treatment before pregnancy, and patients screened and diagnosed with syphilis during pregnancy who had no previous history of anti-syphilis treatment).

Results:

The rate of congenital syphilis in this study was 6.2% (25/406). There was no significant difference in the rate of congenital syphilis between patients who received anti-syphilis treatment before pregnancy and those who did not. Secondary syphilis and high baseline serum TRUST titer (≥1:8) in pregnant women were independent risk factors for congenital syphilis.

Conclusions:

For the prevention of congenital syphilis, anti-syphilis treatment during pregnancy for syphilis seropositive pregnant women is needed, regardless of whether the patient has received anti-syphilis treatment before pregnancy, especially for those patients with secondary syphilis or high baseline serum TRUST titer, thus, timely surveillance, early diagnosis to timely treatment, and close syphilis reexamination during posttreatment follow-up, may help to reduce the above-mentioned risk factors for congenital syphilis.
Sex disparity of lung cancer risk in non-smokers: a multicenter population-based prospective study based on China National Lung Cancer Screening Program
Authors: Wu Zheng , Tan Fengwei , Yang Zhuoyu , Wang Fei , Cao Wei , Qin Chao , Dong Xuesi , Zheng Yadi , Luo Zilin , Zhao Liang , Yu Yiwen , Xu Yongjie , Ren Jiansong , Shi Jufang , Chen Hongda , Li Jiang , Tang Wei , Shen Sipeng , Wu Ning , Chen Wanqing , Li Ni , He Jie
Published: July 2022

Background:

Non-smokers account for a large proportion of lung cancer patients, especially in Asia, but the attention paid to them is limited compared with smokers. In non-smokers, males display a risk for lung cancer incidence distinct from the females—even after excluding the influence of smoking; but the knowledge regarding the factors causing the difference is sparse. Based on a large multicenter prospective cancer screening cohort in China, we aimed to elucidate the interpretable sex differences caused by known factors and provide clues for primary and secondary prevention.

Methods:

Risk factors including demographic characteristics, lifestyle factors, family history of cancer, and baseline comorbidity were obtained from 796,283 Chinese non-smoking participants by the baseline risk assessment completed in 2013 to 2018. Cox regression analysis was performed to assess the sex difference in the risk of lung cancer, and the hazard ratios (HRs) that were adjusted for different known factors were calculated and compared to determine the proportion of excess risk and to explain the existing risk factors.

Results:

With a median follow-up of 4.80 years, 3351 subjects who were diagnosed with lung cancer were selected in the analysis. The lung cancer risk of males was significantly higher than that of females; the HRs in all male non-smokers were 1.29 (95% confidence interval [CI]: 1.20–1.38) after adjusting for the age and 1.38 (95% CI: 1.28–1.50) after adjusting for all factors, which suggested that known factors could not explain the sex difference in the risk of lung cancer in non-smokers. Known factors were 7% (|1.29–1.38|/1.29) more harmful in women than in men. For adenocarcinoma, women showed excess risk higher than men, contrary to squamous cell carcinoma; after adjusting for all factors, 47% ([1.30–1.16]/[1.30–1]) and 4% ([7.02–6.75]/[7.02–1])) of the excess risk was explainable in adenocarcinoma and squamous cell carcinoma. The main causes of gender differences in lung cancer risk were lifestyle factors, baseline comorbidity, and family history.

Conclusions:

Significant gender differences in the risk of lung cancer were discovered in China non-smokers. Existing risk factors did not explain the excess lung cancer risk of all non-smoking men, and the internal causes for the excess risk still need to be explored; most known risk factors were more harmful to non-smoking women; further exploring the causes of the sex difference would help to improve the prevention and screening programs and protect the non-smoking males from lung cancers.
Systematic analysis on expression quantitative trait loci identifies a novel regulatory variant in ring finger and WD repeat domain 3 associated with prognosis of pancreatic cancer
Authors: Zhu Ying , Peng Xiating , Wang Xiaoyang , Ying Pingting , Wang Haoxue , Li Bin , Li Yue , Zhang Ming , Cai Yimin , Lu Zequn , Niu Siyuan , Yang Nan , Zhong Rong , Tian Jianbo , Chang Jiang , Miao Xiaoping
Published: July 2022

Background:

Pancreatic adenocarcinoma (PAAD) is an extremely lethal malignancy. Identification of the functional genes and genetic variants related to PAAD prognosis is important and challenging. Previously identified prognostic genes from several expression profile analyses were inconsistent. The regulatory genetic variants that affect PAAD prognosis were largely unknown.

Methods:

Firstly, a meta-analysis was performed with seven published datasets to systematically explore the candidate prognostic genes for PAAD. Next, to identify the regulatory variants for those candidate genes, expression quantitative trait loci analysis was implemented with PAAD data resources from The Cancer Genome Atlas. Then, a two-stage association study in a total of 893 PAAD patients was conducted to interrogate the regulatory variants and find the prognostic locus. Finally, a series of biochemical experiments and phenotype assays were carried out to demonstrate the biological function of variation and genes in PAAD progression process.

Results:

A total of 128 genes were identified associated with the PAAD prognosis in the meta-analysis. Fourteen regulatory loci in 12 of the 128 genes were discovered, among which, only rs4887783, the functional variant in the promoter of Ring Finger and WD Repeat Domain 3 (RFWD3), presented significant association with PAAD prognosis in both stages of the population study. Dual-luciferase reporter and electrophoretic mobility shift assays demonstrated that rs4887783-G allele, which predicts the worse prognosis, enhanced the binding of transcript factor REST, thus elevating RFWD3 expression. Further phenotypic assays revealed that excess expression of RFWD3 promoted tumor cell migration without affecting their proliferation rate. RFWD3 was highly expressed in PAAD and might orchestrate the genes in the DNA repair process.

Conclusions:

RFWD3 and its regulatory variant are novel genetic factors for PAAD prognosis.
Cardiorespiratory Insufficiency and Performance Fatigability in Women With Systemic Lupus Erythematosus
Authors: Wooten Liana C. , Hasni Sarfaraz , Mikdashi Jamal A. , Keyser Randall E.
Published: July 2022

Purpose:

Patients with systemic lupus erythematosus (SLE) experience excessive, debilitating fatigue with previously reported evidence of etiologically mediated cardiorespiratory impairments. Performance fatigability provides a precise characterization of fatigue as it can be quantified objectively as a function of time, frequency, and/or duration. Nevertheless, little consideration has been given to understanding performance fatigability and its physiological determinants in those with SLE. The purpose of this study was to characterize performance fatigability in patients with SLE, using measures surrounding the anaerobic threshold, with emphasis on cardiorespiratory impairment as a potential mediating factor.

Methods:

This was a case–control study design. 44 physically inactive women, 26 with SLE and 18 controls, completed a treadmill cardiopulmonary exercise test to volitional exhaustion.

Results:

There were no significant differences in age (SLE 34.8(9.0) versus control 36.9(7.3) years;P= .422) between groups. Body mass index (SLE 27.1(5.4) versus control 23.8(5.2) kg/m2;P= .045) was significantly higher in the SLE versus control group. Resting heart rate (SLE 68(16) versus control 78(15) bpm;P= .040) was significantly lower in the SLE compared with the control group. The VO2corresponding to the anaerobic threshold (AT-VO2), used to identify the onset of exercise-induced fatigue, was significantly lower in women with SLE than in controls (SLE 12.4(3.1) versus control 16.4(2.2) ml/kg/min;P< .001), as was AT-stage (SLE 2.5(0.90) versus control 3.4(0.78);P= .002). In addition, the Fatigue Severity Scale (FSS) score was highly and inversely correlated with AT-VO2(rho = −0.615;P< .001), and FSS was highly correlated with the functional aerobic impairment index (rho = 0.663;P< .001).

Conclusions:

This study underscores severe performance fatigability in patients with SLE and its link to cardiorespiratory insufficiency. Physiological presentation of performance fatigability was observed during very low intensities of exercise, emphasizing the negative impact it may have on physical function in this population.
Pediatric Enterococcal Bacteremia: A 12-Year Retrospective Study in a French Pediatric Center
Authors: Bizot Etienne , Truong Jeanne , Mariani-Kurkdjian Patricia , Bonacorsi Stephane , Faye Albert , Caseris Marion
Published: July 2022

Background:

Enterococcal bloodstream infections (EBSIs) are rare infections in children associated with 5%–10% of mortality in previous studies. The recent evolution of antimicrobial resistance and therapies require updated data.

Methods:

We conducted an observational retrospective study between January 2008 and December 2019 describing the characteristics of children with EBSI in a French pediatric hospital. All positive Enterococcus spp. blood cultures associated with sepsis symptoms were analyzed. We also compared characteristics of healthcare-associated infections (HAIs) and community-acquired infections (CAIs) and described antimicrobial resistance evolution during this period.

Results:

In total 74 EBSI were included. Enterococcus faecalis was the most common pathogen (n = 60/74, 81%) followed by Enterococcus faecium (n = 18, 24%), including 4 enterococcal coinfections. EBSIs were mainly associated with central-line associated infection (38%), surgical site infection (14%) or urinary tract infection (11%). An underlying disease was present in 95.9%. However, 4 patients died in the month following the EBSI resulting in a 5.4%, 30-day mortality. All were HAI. HAI (84% of EBSI) was associated with longer bacteremia [31% persistent bacteremia (more than 3 days) versus 0% for CAI; P = 0.029] and more antimicrobial resistance. Amoxicillin resistance is increasing since 2013 in E. faecium (63% in 2013–2019), although high-level gentamicin resistance is stable (19%). Only 1 EBSI due to vancomycin-resistant Enterococcus was described in our cohort, who died.

Conclusions:

EBSIs are rare infections in children mostly described in children with underlying disease. Healthcare-associated bacteremia is associated with higher rates of resistance and poorer prognosis, requiring the involvement of pediatric infectious disease specialists to improve management.
Etiology and Risk Factors for Admission to the Pediatric Intensive Care Unit in Children With Encephalitis in a Developing Country
Authors: Guerrero María P. , Romero Andrés F. , Luengas Miguel , Dávalos Diana M. , Mesa-Monsalve Juan Gonzalo , Vivas-Trochez Rosalba , Camacho-Moreno German , Trujillo-Valencia Mónica , Giraldo Juan P. Calle , Mejía Luis F. , Rojas-Hernández Juan P. , Vinasco Nathaly , Racines Andrea Ruiz , Meléndez Alejandro , Beltrán Claudia P. , López Pio , Chaucanez Yamile , Patiño Jaime , Rodríguez Wilfrido Coronell , Salgado Doris , Martínez Marly , Restrepo Andrea , Márquez Kelly , Galvis Diego , Benavidez Iván , Rojas Christian A. , Cantor Erika , López Medina Eduardo
Published: July 2022

Objective:

To describe a cohort of pediatric patients with encephalitis and their risk factors for admission to the pediatric intensive care unit (PICU).

Study Design:

Children (<18 years old), with encephalitis evaluated by conventional microbiology and syndromic, multiplex test in cerebrospinal fluid (CSF) between July 2017 and July 2020, were recruited from 14 hospitals that comprise the Colombian Network of Encephalitis in Pediatrics. Multivariate analyses were used to evaluate risk factors associated with the need for PICU admission.

Results:

Two hundred two children were included, of which 134 (66.3%) were male. The median age was 23 months (IQR 5.7–73.2). The main etiologies were bacteria (n = 55, 27%), unspecified viral encephalitis (n = 44, 22%) and enteroviruses (n = 27, 13%), with variations according to age group. Seventy-eight patients (38.6%) required management in the PICU. In multivariate analysis, factors associated with admission to the PICU were the presence of generalized seizures (OR 2.73; 95% CI: 1.82–4.11), status epilepticus (OR 3.28; 95% CI: 2.32–4.62) and low leukocyte counts in the CSF (OR 2.86; 95% CI: 1.47–5.57). Compared with enterovirus, bacterial etiology (OR 7.50; 95% CI: 1.0–56.72), herpes simplex encephalitis (OR 11.81; 95% CI: 1.44–96.64), autoimmune encephalitis (OR 22.55; 95% CI: 3.68–138.16) and other viral infections (OR 5.83; 95% CI: 1.09–31.20) increased the risk of PICU admission.

Conclusions:

Data from this national collaborative network of pediatric patients with encephalitis allow early identification of children at risk of needing advanced care and can guide the risk stratification of admission to the PICU.
A Case of the Blues—Colored Pencil Orbitopathy in an 18-Month-Old Boy
Authors: Hwang Christopher J. , Maltry Amanda C. , Harrison Andrew R. , Mokhtarzadeh Ali
Published: July 2022

Orbital penetrating injuries from pencils are rare. This report describes a case of penetrating orbital injury in a young child with a retained blue-colored pencil core foreign body, which led to rapid onset of orbital abscess requiring surgical drainage. Intraoperatively, orbital tissues were stained a bright-blue color. Histopathological study of specimen also highlighted bright blue aggregates of foreign material infiltrating the orbital tissues. Cultures grew Streptococcus mitis and Exophiala jeanselmei, which are rare causes of orbital abscess. Unique properties of retained colored pencil core as compared to graphite pencil core are herein discussed. Due to differences in composition, colored pencil core foreign bodies may require more timely surgical intervention compared to noncolored graphite pencil core.
A Case of Chronic Intranasal Cocaine Abuse Masquerading and Exacerbating Underlying Orbital IgG4-Related Disease
Authors: Bruce Carleigh N. , Clark Thomas J. E. , Ratiani Mariam , Stahulak Andrea , Griepentrog Gregory J.
Published: July 2022

Chronic cocaine use may lead to widespread intranasal inflammation and necrosis. Cases of cocaine use affecting the orbit have been reported in the literature with a clinical spectrum ranging from inflammation-induced p-anti-cytoplasmic neutrophil autoantibodies positive vasculitis to severe midline destructive lesions resulting in orbital apex syndrome. Here, we present a case of chronic intranasal cocaine abuse with midline destruction that initially obscured diagnosis of, and is hypothesized to have exacerbated, underlying IgG4-Related Disease (IgG4-RD) of the orbit over a 2-year period.
Real-life experience of infliximab biosimilar in pediatric-onset inflammatory bowel disease: data from the Sicilian Network for Inflammatory Bowel Disease
Authors: Dipasquale Valeria , Pellegrino Salvatore , Ventimiglia Marco , Cucinotta Ugo , Citrano Michele , Graziano Francesco , Cappello Maria , Busacca Anita , Orlando Ambrogio , Accomando Salvatore , Romano Claudio ,   Sicilian Network for Inflammatory Bowel Disease
Published: July 2022

Objective

To provide data on the use of infliximab biosimilars (IFX-BioS) in children with inflammatory bowel disease (IBD).

Methods

A multicenter, observational, retrospective study was performed among the cohort of the Sicilian Network for IBD. All consecutive IBD children who had at least completed the induction with IFX-BioS from its introduction in Sicily to January 2021 were enrolled. Clinical remission at weeks 14 and 52, treatment persistence, and adverse events were the study outcomes.

Results

Eighty-seven patients [Crohn’s disease (CD): 57.5% and ulcerative colitis (UC): 42.5%] were included: 75 (86.2%) were antitumor necrosis factor-α (anti-TNF-α) agent naïve, while three (3.45%) were switched from the originator to IFX-BioS. Twenty (23%) patients were multiply switched from the biosimilar CT-P13 to SB2 or GP1111 or vice versa. The median follow-up time was 15 months. Clinical remission was achieved by 55.2 and 65.5% of patients at weeks 14 and 52, respectively, with no differences between CD and UC. Dose escalation was needed in 8.0 and 35.7% of patients during induction and maintenance, respectively. Nine adverse events occurred (incidence rate: 6.13/100 person-year). Treatment persistence was 90.8% at 1 year and 75.7% at 2 years (patients on IFX-BioS at 2 years, n = 28). The risk of treatment discontinuation was higher in patients with extraintestinal manifestations (P = 0.018) and in those who were nonnaïve to anti-TNF-α (P = 0.027).

Conclusion

This is the largest cohort of pediatric IBD patients treated with IFX-BioS. Real-life data show that IFX-BioS is efficacious in IBD children, with high percentages of treatment persistence and a low incidence of nonserious adverse events.
Did Age at Surgery Influence Outcome in Patients With Hirschsprung Disease? A Nationwide Cohort Study in the Netherlands
Authors: Roorda Daniëlle , Verkuijl Sanne J. , Derikx Joep P. M. , Trzpis Monika , Meinds Rob J. , Sloots Cornelius E. J. , Witvliet Marieke J. , de Blaauw Ivo , van Gemert Wim G. , van Heurn Lodewijk W. E. , Broens Paul M. A.
Published: July 2022

Objectives:

Hirschsprung disease (HD) requires surgical resection of affected bowel, but the current evidence is inconclusive regarding the optimal age for resection. The aim of this study was to assess whether age at resection of the aganglionic segment is a determinant for surgical outcomes.

Methods:

A cross-sectional cohort study was done including all consecutive patients with HD between 1957 and 2015, aged 8 years or older (n = 830), who were treated in 1 of the 6 pediatric surgical centers in the Netherlands. Outcome measures were mortality, postoperative complications, stoma rate and redo surgery rate, retrieved from the medical records. Additionally, constipation and fecal incontinence rate in long term were assessed with the Defecation and Continence Questionnaire (DeFeC and P-DeFeC).

Results:

The medical records of 830 patients were reviewed, and 346 of the 619 eligible patients responded to the follow-up questionnaires (56%). There was a small increase in the risk of a permanent stoma [odds ratio (OR) 1.01 (95% confidence interval {CI}: 1.00–1.02); P = 0.019] and a temporary stoma [OR 1.01 (95% CI: 1.00–1.01); P = 0.022] with increasing age at surgery, regardless of the length of the aganglionic segment and operation technique. Both adjusted and unadjusted for operation technique, length of disease, and temporary stoma, age at surgery was not associated with the probability and the severity of constipation and fecal incontinence in long term.

Conclusions:

In this study, we found no evidence that the age at surgery influences surgical outcomes, thus no optimal timing for surgery for HD could be determined.
Muscle Strength, Agility, and Body Composition in Children With Intestinal Failure on Parenteral Nutrition
Authors: So Stephanie , Patterson Catherine , Betts Zachary , Belza Christina , Courtney-Martin Glenda , Avitzur Yaron , Wales Paul W.
Published: July 2022

Objectives:

With increasing number of children with intestinal failure (IF) on long-term parenteral nutrition (PN), this study assesses the impact of IF on muscle strength, speed, and agility and body composition (BC), identifying clinical factors that may predict impairment.

Methods:

Cross-sectional study in children 5–18 years with IF on PN. Assessments included Bruininks-Oseretsky Test of Motor Proficiency-2 strength and agility subtest (BOT-2), and grip strength. BC data from dual-energy x-ray absorptiometry (DXA) measurements and clinical variables were collected by chart abstraction. Data were compared to age and sex matched controls and population norms.

Results:

Twenty-one children with IF (14 males), median age 8.33 (IQR: 6.96–11.04) years and 33 controls (20 males), 8.25 (6.67–10.79) years were included. Strength and agility (P< 0.001) and grip strength (P= 0.001) differed between groups. Nine of 21 (43%) of children with IF scored >1 standard deviation (SD) below mean on BOT-2 and 13 of 21 (62%) had grip strength >1 SD below mean. DXA measurements showed 10 of 18 (56%) of children had lower fat-free mass (FFM)% and higher fat mass (FM)% than reference norms. Decreased FFM% was associated with lower BOT-2 scores (r= 0.479;P= 0.044) and grip strength scores >1 SD below mean (P= 0.047). Additional clinical factors significantly impacting strength and agility included prematurity, height, hospitalizations, sepsis, and small bowel length.

Conclusions:

Children with IF are at risk of decreased muscle strength and agility, along with altered BC. Ongoing medical, nutritional, and rehabilitation intervention is vital to optimize outcomes.
Health Care Transition for Adolescents and Young Adults With Pediatric‐Onset Liver Disease and Transplantation
Authors: Vittorio Jennifer , Kosmach‐Park Beverly , King Lindsay Y. , Fischer Ryan , Fredericks Emily M. , Ng Vicky L. , Narang Amrita , Rasmussen Sara , Bucuvalas John
Published: July 2022

Advances in medical therapies and liver transplantation have resulted in a greater number of pediatric patients reaching young adulthood. However, there is an increased risk for medical complications and morbidity surrounding transfer from pediatric to adult hepatology and transplant services. Health care transition (HCT) is the process of moving from a child/family‐centered model of care to an adult or patient‐centered model of health care. Successful HCT requires a partnership between pediatric and adult providers across all disciplines resulting in a transition process that does not end at the time of transfer but continues throughout early adulthood. Joint consensus guidelines in collaboration with the American Society of Transplantation are presented to facilitate the adoption of a structured, multidisciplinary approach to transition planning utilizing The Six Core Elements of Health Care TransitionTM for use by both pediatric and adult specialists. This paper provides guidance and seeks support for the implementation of an HCT program which spans across both pediatric and adult hepatology and transplant centers.
Effect of the COVID-19 Pandemic on Chlamydial Infection Treatment in Women Discharged From an Urban Safety-Net Emergency Unit
Authors: Park Eunsol , Alvarez Kristin S. , Harms Michael , Johnson Courtney , Griffith William
Published: July 2022

Background

Chlamydia is the most frequently reported sexually transmitted infection. COVID-19 exacerbated the challenges in treating and preventing new Chlamydia trachomatis (CT) infections. This study examined the impact of COVID-19 on treating CT-positive patients discharged from a safety-net women's emergency unit.

Methods

This was a preretrospective and postretrospective cohort study. Chlamydia trachomatis–positive female patients seen in the women's emergency unit were evaluated. Patients discharged in 2019, the “pre–COVID-19” group, and those discharged in 2020, the “COVID-19” group, were compared. The primary outcome was CT treatment within 30 days, and secondary outcomes included prescription dispensation, repeat tests taken, and expedited partner treatment. A subgroup of patients discharged before treatment who entered a nurse-led follow-up program was also evaluated.

Results

Of the 1357 cases included, there were no differences in successful 30-day treatment (709 of 789 [89.9%] vs. 568 of 511 [89.9%], P = 0.969) or repeat positive CT test (74 of 333 [22.2%] vs. 46 of 211 [21.8%]), P = 0.36) between pre–COVID-19 and COVID-19. However, the patients who picked up their prescription (196 of 249 [78.7%] vs. 180 of 206 [87.4%], P = 0.021) and those who were prescribed expedited partner therapy (156 of 674 [23.1%] vs. 292 of 460 [63.5%], P < 0.001) increased. Findings in the subgroup of patients who entered the follow-up program were consistent with those in the full cohort.

Conclusions

The COVID-19 pandemic did not change treatment patterns of CT-positive patients in this safety-net women's emergency unit. However, patients were more likely to pick up their medications during COVID-19. Despite the perseverance of these programs through the pandemic, most patients are discharged before positive results, and a fair amount remain untreated.