bluuebunny/crossref_metadata_2025 huggingface dataset:
Association of Race, Ethnicity, and Socioeconomic Status With Esthesioneuroblastoma Presentation, Treatment, and Survival
Authors: Sharma Rahul K. , Irace Alexandria L. , Overdevest Jonathan B. , Turner Justin H. , Patel Zara M. , Gudis David A.
Published: February 2022

Objective

Socioeconomic and other demographic factors are associated with outcomes in head and neck cancer. This study uses a national cancer database to explore how patient race, ethnicity, and socioeconomic status (SES) are associated with esthesioneuroblastoma outcomes, including 5‐year disease‐specific survival (DSS), conditional DSS, stage at diagnosis, and treatment.

Study Design

Retrospective cohort analysis.

Setting

Patients with esthesioneuroblastomas between 1973 and 2015 from the SEER registry (Surveillance, Epidemiology, and End Results).

Methods

The National Cancer Institute Yost Index, a census tract–level composite score composed of 7 parameters, was used to categorize the SES of patients. Kaplan‐Meier analysis and Cox regression were conducted to assess DSS. Conditional DSS was calculated per estimates from simplified Cox models. Logistic regression was conducted to identify risk factors for advanced cancer stage at diagnosis and the likelihood of receiving multimodal therapy.

Results

Complete data were included for 561 patients. DSS was significantly associated with SES (log‐rank, P <. 01) but not race. According to Cox regression, DSS was worse for the lowest SES tertile vs the highest (hazard ratio, 1.70 [95% CI, 1.05‐2.75]; P =. 03). Patients of the lowest SES tertile exhibited an increased risk of advanced cancer stage at diagnosis as compared with the highest SES tertile (odds ratio, 1.84 [95% CI, 1.06‐3.30]; P =. 035). Black patients (odds ratio, 0.44 [95% CI, 0.24‐0.84]; P =. 011) were less likely than other patients to receive multimodal therapy. SES alone was not associated with receiving multimodal therapy.

Conclusion

SES is significantly associated with DSS and conditional DSS for patients with esthesioneuroblastomas. Inequalities in access to care and treatment likely contribute to these disparities.
Limited Open Achilles Repair Without Instrument-Guided Assistance
Authors: Chopra Aman , Parekh Aarav S. , Parekh Selene G.
Published: February 2022

Background:

The limited open Achilles tendon repair technique has recently gained popularity as a treatment option for acute Achilles tendon ruptures. This surgical technique video describes a limited open Achilles tendon repair without instrument guided assistance, demonstrating improved clinical outcomes for patients while also reducing reliance on operative equipment, cost, and the duration of surgery.

Indications:

The indications for this limited open Achilles tendon repair technique include an Achilles tendon rupture less than 6 weeks from injury occurring in the watershed area.

Technique Description:

The patient is prone and a 2- to 3-centimeter longitudinal incision is made over the Achilles tear. In the proximal stump, 3 nonabsorbable sutures are passed horizontally from proximal to distal direction. In the distal stump, the same is done in a nonlocking manner. The stumps are then reflected and the deep fascial compartment is released. The foot is plantarflexed to reduce tension on the repair site. The nonlocking sutures are tied sequentially from distal-distal to proximal-proximal direction. A running box suture using a nonabsorbable suture followed by 0-Vicryl around the rupture site is performed.

Results:

This technique has demonstrated, at a median follow-up of 3.7 years, restored pre-injury function along with no wound complications, re-ruptures, or re-operations in 33 patients. The median time from injury to surgery was 10 (range, 1-45) days and the mean time for returning to pre-injury level of activity was 5.6 (range, 1.7-22.1) months. After the procedure, patients demonstrated significant improvements in mean Foot and Ankle Disability Index (49.1-98.4), mean Visual Analog Scale pain score (4.8-0.2), and mean Foot and Ankle Outcome Score (FAOS) subscales such as FAOS pain (54.8-99.2), FAOS symptoms (84.6-97.0), FAOS activities of daily living (61.4-97.2), FAOS sports and recreational activity (39.5-98.5), and FAOS quality of life (39.7-88.7).

Conclusion:

Patients who underwent a limited open Achilles tendon repair without instrument-guided assistance demonstrated significant improvements in outcome scores with minimal complications.
Circulating tumor DNA predicts therapeutic outcome in mantle cell lymphoma
Authors: Lakhotia Rahul , Melani Christopher , Dunleavy Kieron , Pittaluga Stefania , Saba Nakhle , Lindenberg Liza , Mena Esther , Bergvall Ethan , Lucas Andrea Nicole , Jacob Allison , Yusko Erik , Steinberg Seth M. , Jaffe Elaine S. , Wiestner Adrian , Wilson Wyndham H. , Roschewski Mark
Published: February 2022

Mantle cell lymphoma (MCL) is biologically and clinically heterogeneous and would benefit from prognostic biomarkers to guide management. Circulating tumor DNA (ctDNA) is a novel prognostic biomarker in diffuse large B-cell lymphoma that may have applicability in MCL. We analyzed ctDNA dynamics in previously untreated patients with MCL who received induction therapy with bortezomib and DA-EPOCH-R for 6 cycles followed by random assignment to observation or bortezomib maintenance in responding patients in a prospective phase 2 study. Most patients also underwent initial treatment window of bortezomib alone prior to induction. Serum was collected pretreatment, after the window, after cycles 1 and 2, at the end of induction, and at each follow-up visit along with restaging computed tomography scans. Next-generation sequencing was used to identify and quantify ctDNA encoding the immunoglobulin receptor sequences in serum as markers of minimal residual disease. Fifty-three patients were enrolled, with a median follow-up of 12.7 years. Patients without detectable ctDNA after 2 cycles of induction had longer progression-free survival (PFS) and overall survival (OS) compared with those with detectable ctDNA (median PFS, 2.7 vs 1.8 years; overall P = .005; median OS, 13.8 vs 7.4 years; overall P = .03). Notably, in vivo assessment of ctDNA dynamics during the bortezomib window was not prognostic, and there was no difference in PFS or OS with bortezomib maintenance. ctDNA monitoring after induction showed that molecular relapse preceded clinical relapse in some cases. In conclusion, interim ctDNA negativity strongly correlates with improved survival and supports the investigation of response-adapted strategies. This trial was registered at www.clinicaltrials.gov as #NCT00114738.
Are additional screws required for press-fit fixation of cementless acetabular cups? A systematic review and meta-analysis
Authors: Ni Shenghui , Luo Peng , Guo Lei , Jiang Tianlong
Published: February 2022

Background

Press-fit cementless acetabular cup is widely used in total hip arthroplasty (THA). However, the use of additional screws for the acetabular cup has been extensively debated. The purpose of this review is to compare the stability, revision rate, wear rate, and clinical scores of cementless acetabular cups with and without screws in THA.

Materials and Methods

Comprehensive literature searches of the following databases were performed: Cochrane Library, Pubmed, Web of Science, OVID, Elsevier ClinicalKey, Clinicaltrials.gov, and EMBASE. We searched for trials that compared cementless acetabular cups with screws or without screws, and were published in the English language. We evaluated the stability of the prosthesis by osteolysis and migration. The clinical scores included Harris hip scores (HHS) and pain scores.

Results

Nineteen articles involving 4046 THAs met the inclusion criteria. Our analysis revealed that additional screws did not increase the stability of acetabular cups, and there was no statistical significance between the groups with and without screws in osteolysis and clinically relevant migration. Revision rates showed no significant difference between the groups with and without screws. There was no difference in wear between the two groups. Our analysis showed no difference in pain scores and HHS between groups.

Conclusion

Press-fit without screws could achieve sufficient acetabular cup stability. Acetabular cups without screws showed no difference from acetabular cups with screws in many outcomes. Additional screws are not required for cementless acetabular cups.

Level of evidence: Level III.
Robust meta-analysis for large-scale genomic experiments based on an empirical approach
Authors: Sikdar Sinjini
Published: February 2022

Background

Recent high-throughput technologies have opened avenues for simultaneous analyses of thousands of genes. With the availability of a multitude of public databases, one can easily access multiple genomic study results where each study comprises of significance testing results of thousands of genes. Researchers currently tend to combine this genomic information from these multiple studies in the form of a meta-analysis. As the number of genes involved is very large, the classical meta-analysis approaches need to be updated to acknowledge this large-scale aspect of the data.

Methods

In this article, we discuss how application of standard theoretical null distributional assumptions of the classical meta-analysis methods, such as Fisher’sp-value combination and Stouffer’s Z, can lead to incorrect significant testing results, and we propose a robust meta-analysis method that empirically modifies the individual test statistics andp-values before combining them.

Results

Our proposed meta-analysis method performs best in significance testing among several meta-analysis approaches, especially in presence of hidden confounders, as shown through a wide variety of simulation studies and real genomic data analysis.

Conclusion

The proposed meta-analysis method produces superior meta-analysis results compared to the standardp-value combination approaches for large-scale simultaneous testing in genomic experiments. This is particularly useful in studies with large number of genes where the standard meta-analysis approaches can result in gross false discoveries due to the presence of unobserved confounding variables.
Hospital acquired COVID-19 infections amongst patients before the rollout of COVID-19 vaccinations, a scoping review
Authors: Ngandu Nobubelo K. , Mmotsa Tshiamo M. , Dassaye Reshmi , Thabetha Alice , Odendaal Willem , Langdown Natasha , Ndwandwe Duduzile
Published: February 2022

Background

Hospital settings are at increased risk of spreading Coronavirus Disease 2019 (COVID-19) infections, hence non-pharmaceutical prevention interventions (NPPIs) and prioritized vaccination of healthcare workers and resident patients are critical. The status of COVID-19 hospital acquired infections (HAIs) in low-income settings is unclear. We aimed to identify and summarize the existing evidence on COVID-19 HAIs amongst patients, prior to the rollout of vaccines in countries worldwide.

Methods

We conducted a scoping review of English peer-reviewed literature in PubMed, Web of Science and Scopus using a combination of selected search terms. Full texts articles presenting results on COVID-19 HAIs in hospitalised patients before the rollout of vaccines in countries worldwide were eligible. Data extracted from eligible articles included estimates of COVID-19 HAIs, country, and type of hospital setting, and was summarized narratively. Quality assessment of included articles was not possible.

Results

Literature searches generated a total of 5920 articles, and 45 were eligible for analysis. Eligible articles were from Europe, North America, Asia, and Brazil and none were from low-income countries. The proportion of COVID-19 HAIs ranged from 0% when strict NPPIs were applied, to 65% otherwise. The estimates of COVID-19 HAIs did not differ by country but were lower in studies conducted after implementation of NPPIs and in specialized hospital settings for operative surgery. Studies conducted before the implementation of NPPIs or in long-term care and psychiatric wards often reported high estimates of HAI. Although there was no clear trend in general wards, those situated in academic hospitals managed to reduce HAI rates under strict NPPI protocols. Operative surgery settings, unlike psychiatric settings, effectively prevented COVID-19 HAI using tailored NPPIs.

Conclusion

The available evidence shows a high risk of COVID-19 HAIs, the feasibility of preventing HAIs in different healthcare settings and the importance of appropriately tailored NPPIs. There were no data from low-income settings, therefore, it is unclear whether the reported NPPI approaches could be equally effective elsewhere. We recommend routine monitoring of COVID-19 HAIs in countries with low vaccination coverage, to identify and close gaps in NPPIs and understand gains made from vaccinating healthcare workers and hospitalized patients.
Knowledge, use and attitudes of healthcare professionals towards patient-reported outcome measures (PROMs) at a comprehensive cancer center
Authors: Brunelli Cinzia , Zito Emanuela , Alfieri Sara , Borreani Claudia , Roli Anna , Caraceni Augusto , Apolone Giovanni
Published: February 2022

Background

Despite evidence of the positive impact of routine assessment of patient-reported outcome measures (PROMs), their systematic collection is not widely implemented in cancer care.

Aim

To assess the knowledge, use and attitudes of healthcare professionals (HCPs) towards PROMs and electronically collected PROMs (ePROMs) in clinical practice and research and to explore respondent-related factors associated with the above dimensions.

Method

An ad hoc developed online survey was administered to all HCPs employed in clinical activity in an Italian comprehensive cancer center. The survey investigated which PROMs were known and used, as well as HCPs’ opinions on the advantages and drawbacks of routine PROM assessment, including electronic assessment (ePROM). Linear and logistic regression models were used for association analyses.

Results

Five Hundred Eleven of nine hundred ninety-two invited HCPs (52%) provided analyzable responses. 68% were women, 46% were nurses and 42% physicians, and 52.5% had > 20 years seniority. The average number of PROMs known was six among 17 proposed. All proved to be under-used (< 28%) except unidimensional and multidimensional pain scales (77 and 36%). Respondents expressed an overall positive attitude towards PROMs, with strengths outweighing weaknesses (mean overall scores 3.6 and 2.9, respectively, on a 1–5 scale). 67% of respondents preferred electronic collection over paper and pencil. Profession was associated with knowledge and use (physicians reported knowing more PROMs than other professionals) and with a preference for electronic collection (nurses were less likely to prefer the electronic format than physicians). Senior HCPs were slightly more critical about both PROMs and electronic administration.

Conclusions

This survey indicates an acceptable level of knowledge of common PROM tools but low usage in practice. Based on the generally positive attitude of HCPs, routine implementation of ePROMs can be promoted as long as adequate resources and training are provided.

Trial registration

Not registered.
The efficacy and safety of intravitreal injection of Ranibizumab as pre-treatment for vitrectomy in proliferative diabetic retinopathy with vitreous hemorrhage
Authors: Li Shengguo , Yang Yan , Zou Jingling , Zeng Jun , Ding Chun
Published: February 2022

Background

Intravitreal injection of anti-vascular endothelial growth factor (VEGF) has become first line therapy for diabetic macular edema. This study evaluated the efficacy and safety of intravitreal injection of Ranibizumab (IVR) as pre-treatment for pars plana vitrectomy in proliferative diabetic retinopathy (PDR) patients with vitreous hemorrhage.

Methods

This pilot randomized controlled trial included 48 eyes with vitreous hemorrhage resulting from active PDR. Eyes were treated with IVR 1 or 3 days before vitrectomy or a sham subconjunctival injection 3 days before surgery. The occurrence of new tractional retinal detachment (TRD), total operation time, and intraoperative findings were compared. The concentrations of VEGF and connective tissue growth factor (CTGF) in aqueous humor and plasma collected at the time of IVR and vitrectomy were determined by ELISA.

Results

None of the patients who received IVR experienced new TRD. Ranibizumab injection improved intraoperative outcomes. The mean concentrations of VEGF in aqueous humor were significantly lower after than before IVR in patients who received IVR 1 and 3 days before surgery (P < 0.001 each). The CTGF/log10 (VEGF) ratio was significantly higher after than before IVR in patients who received IVR 3 days before vitrectomy (P = 0.046).

Conclusion

Preoperative IVR is an effective and safe strategy for the surgical treatment of severe PDR combined with vitreous hemorrhage. IVR 1 and 3 days before surgery can significantly reduce VEGF content in aqueous humor and effectively improve intraoperative conditions without causing TRD.

Trial registration

This study was registered with the Chinese Clinical Trial Registry. Name of the registry: Exploratory analysis of effect of intravitreal ranibizumab as pre-treatment for pars plana vitrectomy in proliferative diabetic retinopathy. Trial registration number: ChiCTR-ONC-16009520. Date of registration: October 20, 2016. URL of trial registry record: http://www.chictr.org.cn/searchprojen.aspx
Public health surveillance in the U.S. Department of Veterans Affairs: evaluation of the Praedico surveillance system
Authors: Lucero-Obusan Cynthia , Oda Gina , Mostaghimi Anoshiravan , Schirmer Patricia , Holodniy Mark
Published: February 2022

Background

Early threat detection and situational awareness are vital to achieving a comprehensive and accurate view of health-related events for federal, state, and local health agencies. Key to this are public health and syndromic surveillance systems that can analyze large data sets to discover patterns, trends, and correlations of public health significance. In 2020, Department of Veterans Affairs (VA) evaluated its public health surveillance system and identified areas for improvement.

Methods

Using the Centers for Disease Control and Prevention (CDC) Guidelines for Evaluating Public Health Surveillance Systems, we assessed the ability of the Praedico Surveillance System to perform public health surveillance for a variety of health issues and evaluated its performance compared to an enterprise data solution (VA Corporate Data Warehouse), legacy surveillance system (VA ESSENCE) and a national, collaborative syndromic surveillance platform (CDC NSSP BioSense).

Results

Review of system attributes found that the system was simple, flexible, and stable. Representativeness, timeliness, sensitivity, and Predictive Value Positive were acceptable but could be further improved. Data quality issues and acceptability present challenges that potentially affect the overall usefulness of the system.

Conclusions

Praedico is a customizable surveillance and data analytics platform built on big data technologies. Functionality is straightforward, with rapid query generation and runtimes. Data can be graphed, mapped, analyzed, and shared with key decision makers and stakeholders. Evaluation findings suggest that future development and system enhancements should focus on addressing Praedico data quality issues and improving user acceptability. Because Praedico is designed to handle big data queries and work with data from a variety of sources, it could be enlisted as a tool for interdepartmental and interagency collaboration and public health data sharing. We suggest that future system evaluations include measurements of value and effectiveness along with additional organizations and functional assessments.
A configurable method for clinical quality measurement through electronic health records based on openEHR and CQL
Authors: Li Mengyang , Cai Hailing , Zhi Yunlong , Fu Zehai , Duan Huilong , Lu Xudong
Published: February 2022

Background

One of the primary obstacles to measure clinical quality is the lack of configurable solutions to make computers understand and compute clinical quality indicators. The paper presents a solution that can help clinical staff develop clinical quality measurement more easily and generate the corresponding data reports and visualization by a configurable method based on openEHR and Clinical Quality Language (CQL).

Methods

First, expression logic adopted from CQL was combined with openEHR to express clinical quality indicators. Archetype binding provides the clinical information models used in expression logic, terminology binding makes the medical concepts consistent used in clinical quality artifacts and metadata is regarded as the essential component for sharing and management. Then, a systematic approach was put forward to facilitate the development of clinical quality indicators and the generation of corresponding data reports and visualization. Finally, clinical physicians were invited to test our system and give their opinions.

Results

With the combination of openEHR and CQL, 64 indicators from Centers for Medicare & Medicaid Services (CMS) were expressed for verification and a complicated indicator was shown as an example. 68 indicators from 17 different scenes in the local environment were also expressed and computed in our system. A platform was built to support the development of indicators in a unified way. Also, an execution engine can parse and compute these indicators. Based on a clinical data repository (CDR), indicators were used to generate data reports and visualization and shown in a dashboard.

Conclusion

Our method is capable of expressing clinical quality indicators formally. With the computer-interpretable indicators, a systematic approach can make it more easily to define clinical indicators and generate medical data reports and visualization, and facilitate the adoption of clinical quality measurements.
Diabetes mellitus risk prediction in the presence of class imbalance using flexible machine learning methods
Authors: Sadeghi Somayeh , Khalili Davood , Ramezankhani Azra , Mansournia Mohammad Ali , Parsaeian Mahboubeh
Published: February 2022

Background

Early detection and prediction of type two diabetes mellitus incidence by baseline measurements could reduce associated complications in the future. The low incidence rate of diabetes in comparison with non-diabetes makes accurate prediction of minority diabetes class more challenging.

Methods

Deep neural network (DNN), extremely gradient boosting (XGBoost), and random forest (RF) performance is compared in predicting minority diabetes class in Tehran Lipid and Glucose Study (TLGS) cohort data. The impact of changing threshold, cost-sensitive learning, over and under-sampling strategies as solutions to class imbalance have been compared in improving algorithms performance.

Results

DNN with the highest accuracy in predicting diabetes, 54.8%, outperformed XGBoost and RF in terms of AUROC, g-mean, and f1-measure in original imbalanced data. Changing threshold based on the maximum of f1-measure improved performance in g-mean, and f1-measure in three algorithms. Repeated edited nearest neighbors (RENN) under-sampling in DNN and cost-sensitive learning in tree-based algorithms were the best solutions to tackle the imbalance issue. RENN increased ROC and Precision-Recall AUCs, g-mean and f1-measure from 0.857, 0.603, 0.713, 0.575 to 0.862, 0.608, 0.773, 0.583, respectively in DNN. Weighing improved g-mean and f1-measure from 0.667, 0.554 to 0.776, 0.588 in XGBoost, and from 0.659, 0.543 to 0.775, 0.566 in RF, respectively. Also, ROC and Precision-Recall AUCs in RF increased from 0.840, 0.578 to 0.846, 0.591, respectively.

Conclusion

G-mean experienced the most increase by all imbalance solutions. Weighing and changing threshold as efficient strategies, in comparison with resampling methods are faster solutions to handle class imbalance. Among sampling strategies, under-sampling methods had better performance than others.
Healthcare professionals’ perceptions of childhood obesity in Iquitos, Peru: a qualitative study
Authors: Lai Jo F. , Clarke Joanne , de Wildt Gilles , Meza Graciela , Addo Miriam A. , Gardiner Esme , Khanna Divya
Published: February 2022

Background

Childhood obesity is an urgent worldwide concern associated with increased morbidity in adulthood. Healthcare professionals (HCPs) are well placed to influence childhood obesity trends and implement interventions. English-language studies regarding HCPs’ perceptions of childhood obesity are limited to high-income countries. Peru is an upper-middle-income country with regional disparities in childhood obesity prevalence. This qualitative study aims to explore HCPs’ perceptions of childhood obesity in Iquitos, Peru, where prevalence is relatively low.

Methods

Twenty-one HCPs with child healthcare experience were purposively recruited from two primary healthcare centres. Semi-structured, individual interviews were conducted with a translator and audio recorded. Transcribed data were analysed using thematic analysis.

Results

Eight themes were identified and divided into four categories: (1) HCPs’ perceptions and attitudes towards childhood obesity (level of concern regarding childhood obesity, perceived consequences of childhood obesity); (2) Factors which HCPs perceive to be important in the development of childhood obesity (parental factors, contextual factors); (3) HCPs’ perceptions of their role in childhood obesity prevention and management (educating parents about childhood obesity, regular monitoring of child growth); and (4) Barriers and facilitators in childhood obesity prevention and management (in healthcare, in schools).

Conclusions

HCPs had a low level of concern regarding childhood obesity in Iquitos and prioritised undernutrition. Parental factors were perceived to be the most influential in the development of childhood obesity. HCPs perceived themselves to have minimal influence due to prevailing positive views of excess weight and difficulties engaging parents. Educating parents about childhood obesity was felt to be essential to prevention and management although regular monitoring of child growth and home healthcare visits were viewed as useful additional measures. This study can help to inform the development of targeted public health strategies which are sensitive to local contexts and could prevent the upward childhood obesity trends evident elsewhere in Peru.
Impact of accreditation on health care services performance in Kiryandongo district, Uganda: a longitudinal study
Authors: Matovu Moses , Musiime Elias , Olak Patrick , Mulindwa Muhammad , Namisango Eve , Songwe Kilian
Published: February 2022

Background

The COVID-19 pandemic has emphasised the need for quality laboratory services worldwide. There is renewed focus to strengthen country capacities and laboratories to effectively respond to public health emergencies and patient outcomes. Uganda launched the accreditation program for public health facilities in 2016 with sixteen laboratories. As of June 2021, twenty-three public laboratories have attained ISO 15189:2012 accreditation status. Despite the tremendous achievements of accrediting laboratories in Uganda, laboratory services still face challenges like stock out of commodities and limited testing scopes. We conducted this study to evaluate the impact of accreditation on health care services performance in Kiryandongo district, Uganda.

Methods

We conducted a longitudinal study from January 1, 2020- April 30, 2021 at ten health facilities in Kiryandongo district. We collected health care services performance data from the MoH dhis-2 on selected indicators for HIV, TB, Malaria, Laboratory, Maternal & child health and dhis-2 reporting. We used Generalized Estimating Equations to estimate the impact of accreditation on health care services performance at the different health facilities.

Results

The odds at the accredited facility in comparison to the non-accredited public facilities were; 14% higher for ART enrolment (OR = 1.14, 95% CI: 1.04–1.25), 9% lower for determine testing kits stock out (OR = 0.91, 95% CI: 0.85–0.97), 28% higher for TB case diagnosis (OR = 1.28, 95% CI: 1.10–1.49), 19% higher for TB case enrolment (OR = 1.19, 95% CI: 1.04–1.36), 104% higher for maternity admissions (OR = 2.04, 95% CI: 1.60–2.59), 63% higher for maternity deliveries (OR = 1.63, 95% CI: 1.39–1.90) and 17% higher for reporting hmis 10:01 data to dhis-2 (OR = 1.17, 95% CI: 1.04–1.31).

The odds at the accredited facility in comparison to the non-accredited PNFP facilities were; 26% higher for ART enrolment (OR = 1.26, 95% CI: 1.17–1.36), 33% higher for TB case diagnosis (OR = 1.33, 95% CI: 1.15–1.55), 24% higher for TB case enrolment (OR = 1.24, 95% CI: 1.09–1.42), 136% higher for maternity admissions (OR = 2.36, 95% CI: 1.89–2.94), 76% higher for maternity deliveries (OR = 1.76, 95% CI: 1.51–2.04) and 2% higher for reporting of hmis-10:01 data to dhis-2 (OR = 1.02, 95% CI: 1.01–1.03).

Conclusions

HIV, TB, laboratory, MCH, and reporting to dhis-2 selected indicators were positively impacted by accreditation. This impact translated into increased health care services performance at the accredited facility as compared to the non-accredited facilities.
3T high-resolution magnetic resonance imaging, conventional ultrasonography and ultrasound biomicroscopy of the normal canine eye
Authors: Ivan Daniel , Ohlerth Stefanie , Richter Henning , Verdino Dagmar , Rampazzo Antonella , Pot Simon
Published: February 2022

Background

Advances in MRI coil technology and increased availability of high-field MRI in veterinary medicine enable the acquisition of images of increasingly high spatial resolution while preserving signal-to-noise ratio.The purpose of the present study was to compare 3T high-resolution magnetic resonance imaging (HR-MRI) with ultrasound (US) and ultrasound biomicroscopy (UBM) in the normal canine eye, to assess its potential to depict normal ocular anatomy.

Results

HR-MRI was compared with US and UBM in 10 eyes from 10 healthy beagle dogs. Ocular structures (cornea, anterior chamber, iridocorneal angle, iris, lens, ciliary body, choroid, vitreous body, posterior wall of the eye, optic nerve and optic nerve sheath, extraocular muscles) were assessed subjectively and central corneal thickness (CCT), anterior chamber depth (ACD), aqueous depth (AQD), anteroposterior, mediolateral and dorsoventral lens diameter (APLD, MLLD, DVLD), anteroposterior diameter of the globe including and excluding the scleroretinal rim (APDSRR, APD), vitreous chamber depth (VCD) and optic nerve sheath diameter (ONSD) were measured in HR-MRI and in US. Optic nerve diameter (OND) was measured in HR-MRI. HR-MRI and UBM appearance of the anterior segment were subjectively compared. Detailed reference high-resolution MRI images of normal eyes of Beagle dogs are provided.

Conclusions

HR-MRI allowed assessment of all structures identified with US and UBM. The MRI examinations were performed under general anesthesia with the addition of a neuromuscular blocking agent, while US and UBM examinations were performed in conscious animals. Visibility of the entire ocular wall, the lens, the structures caudal to the ciliary body and the optic nerve and its sheath was superior with HR-MRI. HR-MRI allowed the distinction of retina, choroid and sclera, and the delineation of structures not previously identified in canine eyes with MRI, including Tenon’s capsule and the sub-Tenon’s space.Plane selection was more accurate with HR-MRI compared to US. In general, the range of measurements was narrower for MRI than for US. CCT, AQD, APLD, MLLD, APD, APDSRR and ONSD differed significantly between HR-MRI and US, respectively (p = 0.005-0.027).Micro-MRI may be useful for the assessment of ocular pathologies in the future.
Effect of indacaterol/glycopyrronium on ventilation and perfusion in COPD: a randomized trial
Authors: Singh Dave , Wild Jim M. , Saralaya Dinesh , Lawson Rod , Marshall Helen , Goldin Jonathan , Brown Matthew S. , Kostikas Konstantinos , Belmore Kristin , Fogel Robert , Patalano Francesco , Drollmann Anton , Machineni Surendra , Jones Ieuan , Yates Denise , Tillmann Hanns-Christian
Published: February 2022

Rationale

The long-acting β2-agonist/long-acting muscarinic antagonist combination indacaterol/glycopyrronium (IND/GLY) elicits bronchodilation, improves symptoms, and reduces exacerbations in COPD. Magnetic resonance imaging (MRI) of the lung with hyperpolarized gas and gadolinium contrast enhancement enables assessment of whole lung functional responses to IND/GLY.

Objectives

The primary objective was assessment of effect of IND/GLY on global ventilated lung volume (%VV) versus placebo in COPD. Lung function, regional ventilation and perfusion in response to IND/GLY were also measured.

Methods

This double-blind, randomized, placebo-controlled, crossover study assessed %VV and pulmonary perfusion in patients with moderate-to-severe COPD after 8 days of once-daily IND/GLY treatment (110/50 µg) followed by 8 days of placebo, or vice versa, using inhaled hyperpolarized 3He gas and gadolinium contrast-enhanced MRI, respectively. Lung function measures including spirometry were performed for each treatment after 8 days.

Measurements and main results

Of 31 patients randomized, 29 completed both treatment periods. IND/GLY increased global %VV versus placebo (61.73% vs. 56.73%, respectively, least squares means treatment difference: 5.00% [90% CI 1.40 to 8.60]; P = 0.025). IND/GLY improved whole lung index of ventilation volume to perfusion volume (V/Q) ratio versus placebo; 94% (90% CI 83 to 105) versus 86% (90% CI 75 to 97; P = 0.047), respectively. IND/GLY showed a trend to improve diffusing capacity for carbon monoxide (DLCO) (+ 0.66 mL/min/mmHg; P = 0.082). By Day 8, forced expiratory volume in 1 s (FEV1) was increased by 0.32 L versus placebo (90% CI 0.26 to 0.38; P < 0.0001), substantiating earlier findings and providing evidence of assay sensitivity for this trial.

Conclusions

IND/GLY improved lung ventilation assessed by 3He MRI after 1 week of treatment. This observation may provide mechanistic support for the symptomatic clinical benefit shown with IND/GLY in COPD.

Clinical trial registered with www.clinicaltrials.gov (NCT02634983).
A novel immune-related lncRNA pair signature for prognostic prediction and immune response evaluation in gastric cancer: a bioinformatics and biological validation study
Authors: Wang Jun , Wang Beidi , Zhou Biting , Chen Jing , Qi Jia , Shi Le , Yu Shaojun , Chen Guofeng , Kang Muxing , Jin Xiaoli , Wang Lie , Xu Jinghong , Zhu Linghua , Chen Jian
Published: February 2022

Background

Gastric cancer (GC), the most commonly diagnosed cancer worldwide with poor 5-year survival rate in advanced stages. Although immune-related and survival-related biomarkers, which typically comprise aberrantly expressed long non-coding RNAs (lncRNAs) and genes, have been identified, there are no reports of immune-related lncRNA pair (IRLP) signatures for GC.

Methods

In this study, we acquired lncRNA expression profiles from The Cancer Genome Atlas (TCGA) and used the least absolute shrinkage and selection operator (LASSO) Cox proportional hazards model (iteration = 1000) to develop a IRLP prognostic signature. The area under curve (AUC) was used to assess the prognosis predictive power. The multivariate Cox regression analysis was performed to identify whether this signature was an independent prognostic factor. The immune cell infiltration analysis was performed between the two risk groups. Last, molecular experiments were performed to explore LINC01082 is involved in the development of GC.

Results

We acquired lncRNA expression profiles and used the LASSO Cox model to develop an 18-IRLP signature with a strong prognostic predictive power. The 5-year AUC values of the training, validation, and overall TCGA datasets were 0.77, 0.86, and 0.80, respectively. The different prognostic outcomes between the high- and low-risk groups were determined using our 18-IRLP signature. Moreover, our 18-IRLP signature was an independent prognostic factor as per the multivariate Cox regression analysis, and showed better prognostic evaluation than the traditional TNM staging system as well as other clinical features. We also found differences in cancer-associated fibroblast and macrophage M2 infiltration and the expression of PD-L1, CTLA4, LAG3, and HLA were also observed between the two risk groups (P < 0.05). Analysis of biological functions revealed that target genes of the lncRNAs in the IRLP signature were enriched in focal adhesion and regulation of actin cytoskeleton. Finally, as one of significant candidates of IRLP signature, overexpression of LINC01082 suppressed the invasion ability of GC cells as well as PD-L1 expression profiles.

Conclusions

Our novel 18-IRLP signature provides new insights regarding immunological biomarkers, imparts a better understanding of the tumor immune microenvironment, and can be used for predicting prognosis and evaluating immune response in GC.
Clinical pharmacokinetics of quinine and its relationship with treatment outcomes in children, pregnant women, and elderly patients, with uncomplicated and complicated malaria: a systematic review
Authors: Saeheng Teerachat , Na-Bangchang Kesara
Published: February 2022

Background

Standard dosage regimens of quinine formulated for adult patients with uncomplicated and complicated malaria have been applied for clinical uses in children, pregnant women, and elderly. Since these populations have anatomical and physiological differences from adults, dosage regimens formulated for adults may not be appropriate. The study aimed to (i) review existing information on the pharmacokinetics of quinine in children, pregnant women, and elderly populations, (ii) identify factors that influence quinine pharmacokinetics, and (iii) analyse the relationship between the pharmacokinetics and treatment outcomes (therapeutic and safety) of various dosage regimens of quinine.

Methods

Web of Sciences, Cochrane Library, Scopus, and PubMed were the databases applied in this systematic search for relevant research articles published up to October 2020 using the predefined search terms. The retrieved articles were initially screened by titles and abstracts to exclude any irrelevant articles and were further evaluated based on full-texts, applying the predefined eligibility criteria. Excel spreadsheet (Microsoft, WA, USA) was used for data collection and management. Qualitative data are presented as numbers and percentages, and where appropriate, mean + SD or median (range) or range values.

Results

Twenty-eight articles fulfilled the eligibility criteria, 19 in children, 7 in pregnant women, and 2 in elderly (14 and 7 articles in complicated and uncomplicated malaria, respectively). Severity of infection, routes of administration, and nutritional status were shown to be the key factors impacting quinine pharmacokinetics in these vulnerable groups.

Conclusions

The recommended dosages for both uncomplicated and complicated malaria are, in general, adequate for elderly and children with uncomplicated malaria. Dose adjustment may be required in pregnant women with both uncomplicated and complicated malaria, and in children with complicated malaria. Pharmacokinetics studies relevant to clinical efficacy in these vulnerable groups of patients with large sample size and reassessment of MIC (minimum inhibitory concentration) should be considered.
Association between increasing agricultural use of 2,4-D and population biomarkers of exposure: findings from the National Health and Nutrition Examination Survey, 2001–2014
Authors: Freisthler Marlaina S. , Robbins C. Rebecca , Benbrook Charles M. , Young Heather A. , Haas David M. , Winchester Paul D. , Perry Melissa J.
Published: February 2022

Background

2,4-Dichlorophenoxyacetic acid (2,4-D) is one of the most extensively used herbicides in the United States. In 2012, 2,4-D was the most widely used herbicide in non-agricultural settings and the fifth most heavily applied pesticide in the US agricultural sector. The objective of this study was to examine trends in 2,4-D urinary biomarker concentrations to determine whether increases in 2,4-D application in agriculture are associated with increases in biomonitoring levels of urine 2,4-D.

Methods

Data from the National Health and Nutrition Examination Survey (NHANES) with available urine 2,4-D biomarker measurements from survey cycles between 2001 and 2014 were utilized. Urine 2,4-D values were dichotomized using the highest limit of detection (LOD) across all cycles (0.40 μg/L or 0.4 ppb). Agricultural use of 2,4-D was estimated by compiling publicly available federal and private pesticide application data. Logistic regression models adjusted for confounders were fitted to evaluate the association between agricultural use of 2,4-D and urine 2,4-D level above the dichotomization threshold.

Results

Of the 14,395 participants included in the study, 4681 (32.5%) had urine 2,4-D levels above the dichotomization threshold. The frequency of participants with high 2,4-D levels increased significantly (p < .0001), from a low of 17.1% in 2001–2002 to a high of 39.6% in 2011–2012. The adjusted odds of high urinary 2,4-D concentrations associated with 2,4-D agricultural use (per ten million pounds applied) was 2.268 (95% CI: 1.709, 3.009). Children ages 6–11 years (n = 2288) had 2.1 times higher odds of having high 2,4-D urinary concentrations compared to participants aged 20–59 years. Women of childbearing age (age 20–44 years) (n = 2172) had 1.85 times higher odds than men of the same age.

Conclusions

Agricultural use of 2,4-D has increased substantially from a low point in 2002 and it is predicted to increase further in the coming decade. Because increasing use is likely to increase population level exposures, the associations seen here between 2,4-D crop application and biomonitoring levels require focused biomonitoring and epidemiological evaluation to determine the extent to which rising use and exposures cause adverse health outcomes among vulnerable populations (particularly children and women of childbearing age) and highly exposed individuals (farmers, other herbicide applicators, and their families).
Population snapshot of the extended-spectrum β-lactamase-producing Escherichia coli invasive strains isolated from a Hungarian hospital
Authors: Tóth Kinga , Tóth Ákos , Kamotsay Katalin , Németh Viktória , Szabó Dóra
Published: February 2022

Background

This study was carried out to determine the prevalence and the genetic background of extended-spectrum β-lactamase-producing Escherichia coli invasive isolates obtained from a tertiary-care hospital in Budapest, Hungary.

Methods

Between October–November 2018, all invasive ESBL-producing E. coli isolates were collected from Central Hospital of Southern Pest. The antimicrobial susceptibility testing was performed according to the EUCAST guidelines. The possible clonal relationships were investigated by core genome (cg)MLST (SeqSphere +) using whole-genome sequencing (WGS) data of isolates obtained from Illumina 251-bp paired-end sequencing. From WGS data acquired antimicrobial resistance genes, virulence genes and replicon types were retrieved using ResFinder3.1, PlasmidFinder2.1, pMLST-2.0, VirulenceFinder2.0 and Virulence Factors Database online tools.

Results

Overall, six E. coli isolates proved to be resistant to third-generation cephalosporins and ESBL-producers in the study period. Full genome sequence analysis showed that five E. coli isolates belonged to the ST131 clone: two to C1-M27 subclade with blaCTX-M-27 and three to C2/H30Rx subclade with blaCTX-M-15. One isolate belonged to ST1193 with blaCTX-M-27. According to cgMLST, all C2/H30Rx isolates formed a cluster (≤ 6 allele differences), while the blaCTX-M-27-producing C1-M27 isolates differed at least 35 alleles from each other. Both C2/H30Rx and C1-M27 ST131 isolates harbored similar antimicrobial resistance gene sets. However, only C2/H30Rx isolates had the qnrB and aac(3)-IIa. The isolates carried similar extraintestinal virulence gene set but differed in some genes encoding siderophores, protectins and toxins. Moreover, only one C2/H30Rx isolate carried salmochelin siderophore system and showed virotype B. All isolates showed resistance against ceftriaxone, cefotaxime, and ciprofloxacin, and the C2/H30Rx isolates were also resistant to gentamicin, tobramycin, and ceftazidime.

Conclusions

Out of six ESBL-producing E. coli, five belonged to the ST131 clone. This study indicates, that the C2/H30Rx and C1-M27 subclades of the ST131 appear to be the dominant clones collected in a Hungarian hospital.
Causes, clinical findings and therapeutic options in chylomicronemia syndrome, a special form of hypertriglyceridemia
Authors: Paragh György , Németh Ákos , Harangi Mariann , Banach Maciej , Fülöp Péter
Published: February 2022

The prevalence of hypertriglyceridemia has been increasing worldwide. Attention is drawn to the fact that the frequency of a special hypertriglyceridemia entity, named chylomicronemia syndrome, is variable among its different forms. The monogenic form, termed familial chylomicronemia syndrome, is rare, occuring in 1 in every 1 million persons. On the other hand, the prevalence of the polygenic form of chylomicronemia syndrome is around 1:600. On the basis of the genetical alterations, other factors, such as obesity, alcohol consumption, uncontrolled diabetes mellitus and certain drugs may significantly contribute to the development of the multifactorial form. In this review, we aimed to highlight the recent findings about the clinical and laboratory features, differential diagnosis, as well as the epidemiology of the monogenic and polygenic forms of chylomicronemias. Regarding the therapy, differentiation between the two types of the chylomicronemia syndrome is essential, as well. Thus, proper treatment options of chylomicronemia and hypertriglyceridemia will be also summarized, emphasizing the newest therapeutic approaches, as novel agents may offer solution for the effective treatment of these conditions.
Interleukin-4 can play a role in allergic rhinitis patient during treatment with Zataria multiflora
Authors: Ariaee Nazila , Yadegari Yaser , Shabestari Mohamad , Asili Javad , Panahi Maryam , Ghorbani Jalal , Jabbari Farahzad
Published: February 2022

Background

Allergic rhinitis is a widespread disorder across the globe. The Shirazi thyme (Zataria multiflora) has been shown to have considerable antioxidant and anti-inflammatory properties. This study assessed the effect of this herbal product on alterations in inflammatory/anti-inflammatory cytokines.

Method

This study was conducted on the bank sample before and after the intervention to measure interleukin-4, interleukin-5, and interferon -γ levels with the ELISA test method in a supernatant taken from the PBMC cell culture from 30 allergic rhinitis patients.

Results

The IL-4 level had no significant difference between the two groups before the treatment. However, it had a significant increase in the case group after the treatment. The IL-5 level was significantly higher in the case group before the treatment. Nevertheless, there were no significant differences between the case and control groups after the treatment. Similarly, no significant differences were observed between the two groups considering IFN-γ before and after the treatment.

Conclusion

Consuming thyme with an increase in anti-inflammatory cytokine IL-4 and a decrease in IL-5 cytokine control inflammation and improvement in allergic rhinitis symptoms.

Clinical trial details This clinical trial study was recorded at 22.5.2014 in the Iran Registry of Clinical Trials code: (IRCT2016121823235N6) https://www.irct.ir/trial/19852