bluuebunny/crossref_metadata_2025 huggingface dataset:
A Curriculum for Enhancing Physician Teaching Skills: The Value of Physician-Educator Partnerships
Authors: Hoffert Mara M , Passalacqua Karla D , Haftka-George Alexis , Abreu Lanfranco Odaliz , Martin Robert A
Published: July 2021

Developing as a physician requires an enormous amount of complex training, and quality of instruction greatly affects training outcomes. But while physicians are expected to teach trainees within the clinic, they often do not receive formal training in effective instructional practices. Providing faculty development programs is one way that institutions can help physicians develop teaching skills, but these programs often are developed without the input of educational specialists and not based in educational theory. In this methodology paper, we describe a 5-module curriculum that was developed in a cross-disciplinary collaboration between instructional designers and physician faculty. By merging educational and medical expertise and using adult learning theory with the Charlotte-Danielson educational framework, an essentials for clinical teaching educational endorsement program (ECTEEP) was created as a feature of the institutional curriculum within a large, urban teaching hospital. Here we describe how the program was developed through a physician-educator partnership, outline the program’s key content, and highlight essential aspects of successful implementation. The ECTEEP incorporates active learning approaches within an abbreviated format, distilling 5 critical aspects of effective teaching that are relevant to the clinical environment: cultural humility and safe learning environments, instruction practices for engaging learners, instruction and assessment strategies, receiving and giving feedback, and mentorship and coaching. A central feature of the program is that facilitators actively model the teaching behaviors they are conveying, which underscores the critical importance of facilitator preparation and skill. Our curriculum is offered here as a basic template for institutions that may want to establish a program for enhancing physician teaching skill.
Language as an Identity: Hindi–Non-Hindi Debates in India
Authors: Ranjan Amit
Published: July 2021

Non-Hindi speakers in India always accuse that Hindi is imposed on them. As language is an essential component of an individual's and group's identity particularly in the Indian state of Tamil Nadu, Hindi is largely seen as Aryan's language spoken by north Indians. Tensions between Hindi and non-Hindi language have roots in the British India. There were demands for linguistic states in colonial years that accelerated in post-independent India. Although an idea to create states based on language were not accepted by early Indian leadership, they were gradually created. This paper attempts to critically examine the politics of language-based identity and related tensions.
Systemic sclerosis portends increased risk of conduction and rhythm abnormalities at diagnosis and during disease course: A US population-based cohort
Authors: Radwan Yasser A , Kurmann Reto D , Sandhu Avneek S , El-Am Edward A , Crowson Cynthia S , Matteson Eric L , Osborn Thomas G , Warrington Kenneth J , Mankad Rekha , Makol Ashima
Published: July 2021

Objectives:

To study the incidence, risk factors, and outcomes of conduction and rhythm disorders in a population-based cohort of patients with systemic sclerosis versus nonsystemic sclerosis comparators.

Methods:

An incident cohort of patients with systemic sclerosis (1980–2016) from Olmsted County, MN, was compared to age- and sex-matched nonsystemic sclerosis subjects (1:2). Electrocardiograms, Holter electrocardiograms, and a need for cardiac interventions were reviewed to determine the occurrence of any conduction or rhythm abnormalities.

Results:

Seventy-eight incident systemic sclerosis cases and 156 comparators were identified (mean age 56 years, 91% female). The prevalence of any conduction disorder before systemic sclerosis diagnosis compared to nonsystemic sclerosis subjects was 15% versus 7% ( p = 0.06), and any rhythm disorder was 18% versus 13% ( p = 0.33). During a median follow-up of 10.5 years in patients with systemic sclerosis and 13.0 years in nonsystemic sclerosis comparators, conduction disorders developed in 25 patients with systemic sclerosis with cumulative incidence of 20.5% (95% confidence interval: 12.4%–34.1%) versus 28 nonsystemic sclerosis patients with cumulative incidence of 10.4% (95% confidence interval: 6.2%–17.4%) (hazard ratio: 2.57; 95% confidence interval: 1.48–4.45), while rhythm disorders developed in 27 patients with systemic sclerosis with cumulative incidence of 27.3% (95% confidence interval: 17.9%–41.6%) versus 43 nonsystemic sclerosis patients with cumulative incidence of 18.0% (95% confidence interval: 12.3%–26.4%) (hazard ratio: 1.62; 95% confidence interval: 1.00–2.64). Age, pulmonary hypertension, and smoking were identified as risk factors.

Conclusion:

Patients with systemic sclerosis have an increased risk of conduction and rhythm disorders both at disease onset and over time, compared to nonsystemic sclerosis patients. These findings warrant increased vigilance and screening for electrocardiogram abnormalities in systemic sclerosis patients with pulmonary hypertension.
The Spectrum of Antireflux Surgery in the Management of GERD
Authors: Swanstrom Lee L.
Published: July 2021

Only a small percentage of patients end up seeing a surgeon for GERD. This paper discusses the patients the surgeon typically sees, the patient selection process, and the process of choosing the best intervention for the patient in order to achieve optimal outcomes, which in turn are a balance between symptom relief/disease cure versus complication risk and side effects of the procedure.
MUREN: a robust and multi-reference approach of RNA-seq transcript normalization
Authors: Feng Yance , Li Lei M.
Published: July 2021

Background

Normalization of RNA-seq data aims at identifying biological expression differentiation between samples by removing the effects of unwanted confounding factors. Explicitly or implicitly, the justification of normalization requires a set of housekeeping genes. However, the existence of housekeeping genes common for a very large collection of samples, especially under a wide range of conditions, is questionable.

Results

We propose to carry out pairwise normalization with respect to multiple references, selected from representative samples. Then the pairwise intermediates are integrated based on a linear model that adjusts the reference effects. Motivated by the notion of housekeeping genes and their statistical counterparts, we adopt the robust least trimmed squares regression in pairwise normalization. The proposed method (MUREN) is compared with other existing tools on some standard data sets. The goodness of normalization emphasizes on preserving possible asymmetric differentiation, whose biological significance is exemplified by a single cell data of cell cycle. MUREN is implemented as an R package. The code under license GPL-3 is available on the github platform: github.com/hippo-yf/MUREN and on the conda platform: anaconda.org/hippo-yf/r-muren.

Conclusions

MUREN performs the RNA-seq normalization using a two-step statistical regression induced from a general principle. We propose that the densities of pairwise differentiations are used to evaluate the goodness of normalization. MUREN adjusts the mode of differentiation toward zero while preserving the skewness due to biological asymmetric differentiation. Moreover, by robustly integrating pre-normalized counts with respect to multiple references, MUREN is immune to individual outlier samples.
Circulating angiogenic factors and HIV among pregnant women in Zambia: a nested case–control study
Authors: Smithmyer Megan E. , Mabula-Bwalya Chileshe M. , Mwape Humphrey , Chipili Gabriel , Spelke Bridget M. , Kasaro Margaret P. , De Paris Kristina , Vwalika Bellington , Sebastião Yuri V. , Stringer Jeffrey S.A. , Price Joan T.
Published: July 2021

Background

Maternal HIV increases the risk of adverse birth outcomes including preterm birth, fetal growth restriction, and stillbirth, but the biological mechanism(s) underlying this increased risk are not well understood. We hypothesized that maternal HIV may lead to adverse birth outcomes through an imbalance in angiogenic factors involved in the vascular endothelial growth factor (VEGF) signaling pathway.

Methods

In a case–control study nested within an ongoing cohort in Zambia, our primary outcomes were serum concentrations of VEGF-A, soluble endoglin (sEng), placental growth factor (PlGF), and soluble fms-like tyrosine kinase-1 (sFLT-1). These were measured in 57 women with HIV (cases) and 57 women without HIV (controls) before 16 gestational weeks. We used the Wilcoxon rank-sum and linear regression controlling for maternal body mass index (BMI) and parity to assess the difference in biomarker concentrations between cases and controls. We also used logistic regression to test for associations between biomarker concentration and adverse pregnancy outcomes (preeclampsia, preterm birth, small for gestational age, stillbirth, and a composite of preterm birth or stillbirth).

Results

Compared to controls, women with HIV had significantly lower median concentrations of PlGF (7.6 vs 10.2 pg/mL, p = 0.02) and sFLT-1 (1647.9 vs 2055.6 pg/mL, p = 0.04), but these findings were not confirmed in adjusted analysis. PlGF concentration was lower among women who delivered preterm compared to those who delivered at term (6.7 vs 9.6 pg/mL, p = 0.03) and among those who experienced the composite adverse birth outcome (6.2 vs 9.8 pg/mL, p = 0.02). Median sFLT-1 concentration was lower among participants with the composite outcome (1621.0 vs 1945.9 pg/mL, p = 0.04), but the association was not significant in adjusted analysis. sEng was not associated with either adverse birth outcomes or HIV. VEGF-A was undetectable by Luminex in all specimens.

Conclusions

We present preliminary findings that HIV is associated with a shift in the VEGF signaling pathway in early pregnancy, although adjusted analyses were inconclusive. We confirm an association between angiogenic biomarkers and adverse birth outcomes in our population. Larger studies are needed to further elucidate the role of HIV on placental angiogenesis and adverse birth outcomes.
Cell fusion enhances energy metabolism of mesenchymal tumor hybrid cells to sustain their proliferation and invasion
Authors: Brito Ariadna , Merle Candice , Lagarde Pauline , Faustin Benjamin , Devin Anne , Lartigue Lydia , Chibon Frederic
Published: July 2021

Background

Cell-to-cell fusion is emerging as a key element of the metastatic process in various cancer types. We recently showed that hybrids made from the spontaneous merging of pre-malignant (IMR90 E6E7, i.e. E6E7) and malignant (IMR90 E6E7 RST, i.e. RST) mesenchymal cells recapitulate the main features of human undifferentiated pleomorphic sarcoma (UPS), with a highly rearranged genome and increased spreading capacities. To better characterize the intrinsic properties of these hybrids, we investigated here their metabolic energy profile compared to their parents.

Results

Our results unveiled that hybrids harbored a Warburg-like metabolism, like their RST counterparts. However, hybrids displayed a much greater metabolic activity, enhancing glycolysis to proliferate. Interestingly, modifying the metabolic environmental conditions through the use of 5-aminoimidazole-4-carbox-amide-1-β-D-ribofuranoside (AICAR), an activator of the 5′-adenosine monophosphate (AMP)-activated protein kinase (AMPK), specifically reduced the growth of hybrids, and also abrogated the invasive capacity of hybrids displaying enhanced glycolysis. Furthermore, AICAR efficiently blocked the tumoral features related to the aggressiveness of human UPS cell lines.

Conclusion

Altogether, our findings strongly suggest that hybrids rely on higher energy flux to proliferate and that a drug altering this metabolic equilibrium could impair their survival and be potentially considered as a novel therapeutic strategy.
COVID-19 pandemic related long-term chronic stress on the prevalence of depression and anxiety in the general population
Authors: Qi Tian , Hu Ting , Ge Qi-Qi , Zhou Xiao-Na , Li Jia-Mei , Jiang Chun-Lei , Wang Wei
Published: July 2021

Background

The COVID-19 pandemic has lasted for more than 1 year, causing far-reaching and unprecedented changes in almost all aspects of society. This study aimed to evaluate the long-term consequences of the COVID-19 pandemic on depression and anxiety, and explore the factors associated with it.

Methods

A cross-sectional study using an online survey was conducted to assess mental health problems from February 2 to February 9, 2021 by using patient health questionnaire-9 (PHQ-9) and generalized anxiety disorder-7 (GAD-7). The insomnia severity index (ISI), demographic data and COVID-19 related variables were measured by a self-designed questionnaire. The factors associated with depressive and anxiety symptoms were identified by Pearson chi-square test and binary logistic regression analysis.

Results

In the study that 1171 participants enrolled, the overall prevalence of depressive and anxiety symptoms among general people was 22.6 and 21.4% respectively in the present study. Living alone was a potential risk factor for depressive symptoms, while regular exercises was a potential protective factor. The prevalence of depressive and anxiety symptoms was significantly associated with the severity of insomnia symptoms and the negative feelings about pandemic.

Conclusion

COVID-19 pandemic- related chronic stress has brought about profound impacts on long-term mental health in the general population. The level of insomnia and a negative attitude towards the pandemic are significantly correlated with unfavorable mental health. However, we failed to found a significant association of age and gender with the mental health symptoms, although they were recognized as well-established risk factors during the outbreak by some other studies. This discrepancy may be because the acute and chronic effects of the pandemic are influenced by different factors, which reminds that more attention should be paid to the intrinsic psychological factors and physical reactions towards COVID-19.
Transparent reporting of recruitment and informed consent approaches in clinical trials recruiting children with minor parents in sub-Saharan Africa: a secondary analysis based on a systematic review
Authors: De Pretto-Lazarova Angela , Brancati-Badarau Domnita Oana , Burri Christian
Published: July 2021

Background

Standardised checklists of items to be addressed in clinical study protocols and publications are promoting transparency in research. However, particular specifications for exceptional cases, such as children with minor parents are missing. This study aimed to examine the level of transparency regarding recruitment and informed consent approaches in publications of clinical trials recruiting children with minor parents in sub-Saharan Africa. We thereby focused particularly on the transparency about consenting persons (i.e. proxy decision-makers) and assessed the need to expand reporting guidelines for such exceptional cases.

Methods

We conducted a secondary analysis of clinical trial publications previously identified through a systematic review. Multiple scientific databases were searched up to March 2019. Clinical trial publications addressing consent and potentially recruiting children with minor parents in sub-Saharan Africa were included. 44 of the in total 4382 screened articles met our inclusion criteria. A descriptive analysis was performed.

Results

None of the included articles provided full evidence on whether any recruited children had minor parents and how consent was obtained for them. Four proxy decision-maker types were identified (parents; parents or guardians; guardians; or caregivers), with further descriptions provided rarely and mostly in referenced clinical trial registrations or protocols. Also, terminology describing proxy decision-makers was often used inconsistently.

Conclusions

Reporting the minimum maternal age alongside maternal data provided in baseline demographics can increase transparency on the recruitment of children with minor mothers. The CONSORT checklist should require clinical trial publications to state or reference exceptional informed consent procedures applied for special population groups. A standardized definition of proxy decision-maker types in international clinical trial guidelines would facilitate correct and transparent informed consent for children and children with minor parents.

Study registration

CRD42018074220.
What have we learned about COVID-19 volunteering in the UK? A rapid review of the literature
Authors: Mao Guanlan , Fernandes-Jesus Maria , Ntontis Evangelos , Drury John
Published: July 2021

Background

Community engagement and volunteering are essential for the public response to COVID-19. Since March 2020 a large number of people in the UK have been regularly doing unpaid activities to benefit others besides their close relatives. Although most mutual aid groups emerged from local neighbourhoods and communities, official public institutions also fostered community volunteering, namely through the community champions scheme. By considering a broad definition of COVID-19 volunteering, this article describes a systematic review of the literature focused on one broad question: What have we learned about COVID-19 volunteering both at the UK national level and the more local community level?

Methods

A rapid review of the literature in peer-reviewed databases and grey literature was applied in our search, following the PRISMA principles. The search was conducted from 10 to 16 of October 2020, and sources were included on the basis of having been published between January and October 2020, focusing on COVID-19 and addressing community groups, volunteering groups, volunteers, or community champions in the UK.

Results

After initial screening, a total of 40 relevant sources were identified. From these, 27 were considered eligible. Findings suggest that food shopping and emotional support were the most common activities, but there were diverse models of organisation and coordination in COVID-19 volunteering. Additionally, community support groups seem to be adjusting their activities and scope of action to current needs and challenges. Volunteers were mostly women, middle-class, highly educated, and working-age people. Social networks and connections, local knowledge, and social trust were key dimensions associated with community organising and volunteering. Furthermore, despite the efforts of a few official public institutions and councils, there has been limited community engagement and collaboration with volunteering groups and other community-based organisations.

Conclusions

We identified important factors for fostering community engagement and COVID-19 volunteering as well as gaps in the current literature. We suggest that future research should be directed towards deepening knowledge on sustaining community engagement, collaboration and community participation over time, during and beyond this pandemic.
Factors influencing childhood immunisation uptake in Africa: a systematic review
Authors: Galadima Abubakar Nasiru , Zulkefli Nor Afiah Mohd , Said Salmiah Md , Ahmad Norliza
Published: July 2021

Background

Vaccine preventable diseases are still the most common cause of childhood mortality, with an estimated 3 million deaths every year, mainly in Africa and Asia. An estimate of 29% deaths among children aged 1–59 months were due to vaccine preventable diseases. Despite the benefits of childhood immunisation, routine vaccination coverage for all recommended Expanded Programme on Immunization vaccines has remained poor in some African countries, such as Nigeria (31%), Ethiopia (43%), Uganda (55%) and Ghana (57%). The aim of this study is to collate evidence on the factors that influence childhood immunisation uptake in Africa, as well as to provide evidence for future researchers in developing, implementing and evaluating intervention among African populations which will improve childhood immunisation uptake.

Methods

We conducted a systematic review of articles on the factors influencing under-five childhood immunisation uptake in Africa. This was achieved by using various keywords and searching multiple databases (Medline, PubMed, CINAHL and Psychology & Behavioral Sciences Collection) dating back from inception to 2020.

Results

Out of 18,708 recorded citations retrieved, 10,396 titles were filtered and 324 titles remained. These 324 abstracts were screened leading to 51 included studies. Statistically significant factors found to influence childhood immunisation uptake were classified into modifiable and non-modifiable factors and were further categorised into different groups based on relevance. The modifiable factors include obstetric factors, maternal knowledge, maternal attitude, self-efficacy and maternal outcome expectation, whereas non-modifiable factors were sociodemographic factors of parent and child, logistic and administration factors.

Conclusion

Different factors were found to influence under-five childhood immunisation uptake among parents in Africa. Immunisation health education intervention among pregnant women, focusing on the significant findings from this systematic review, would hopefully improve childhood immunisation uptake in African countries with poor coverage rates.
Teaching plain language to medical students: improving communication with disadvantaged patients
Authors: Sagi Doron , Spitzer-Shohat Sivan , Schuster Michal , Daudi Ligat , Rudolf Mary Catharine Joy
Published: July 2021

Background

Low health literacy underpins health inequality and leads to poor adherence to medical care and higher risk of adverse events and rehospitalization. Communication in plain language, therefore, is an essential skill for health professionals to acquire. Most medical education communication skill programs focus on verbal communication, while written communication training is scarce.

ETGAR is a student delivered service for vulnerable patients after hospital discharge in which, amongst other duties, students ‘translate’ the medical discharge letters into plain language and share them with patients at a home visit. This study ascertains how this plain language training impacted on students’ written communication skills using a tool designed for purpose.

Methods

Students, in pairs, wrote three plain language discharge letters over the course of a year for patients whom they encountered in hospital. The students handed over and shared the letters with the patients during a post-discharge home visit. Structured feedback from course instructors was given for each letter. An assessment tool was developed to evaluate students’ ability to tell the hospitalization narrative using plain and clear language. First and last letters were blindly evaluated for the entire cohort (74 letters; 87 students).

Results

Students scored higher in all assessment categories in the third letters, with significant improvement in overall score 3.5 ± 0.8 vs 4.1 ± 0.6 Z = -3.43, p = 0.001. The assessment tool’s reliability was high α = 0.797, it successfully differentiated between plain language categories, and its score was not affected by letter length or patient’s medical condition.

Conclusions

Plain language discharge letters written for real patients in the context of experience-based learning improved in quality, providing students with skills to work effectively in an environment where poor health literacy is prevalent. ETGAR may serve as a model for learning written communication skills during clinical years, using the assessment tool for formative or summative evaluation.
Effectiveness of data auditing as a tool to reinforce good research data management (RDM) practice: a Singapore study
Authors: Lau Hui Xing , Lee Ser Lin Celine , Ali Yusuf
Published: July 2021

Background

Institutions, funding agencies and publishers are placing increasing emphasis on good research data management (RDM). RDM lapses in medical science can result in questionable data and cause the public’s confidence in the scientific community to crumble. A fledgling medical school in a young university in Singapore has mandated every funded research project to have a data management plan (DMP). However, researchers’ adherence to their DMPs was unknown until the school embarked on routine data auditing. We hypothesize that research data auditing improves RDM awareness, compliance and reception in the school.

Methods

We conducted surveys with research PIs and researchers before and after data auditing to evaluate differences in self-reported RDM awareness, compliance and reception. As it is mandatory to deposit research data in a central data repository system in the school, we tracked data deposition by each laboratory from 2 weeks before to 3 months after data auditing as a marker of actual RDM compliance.

Results

Research data auditing had an overall positive effect on self-reported RDM awareness, compliance and reception for both research PIs and researchers. Research PIs agreed more that RDM was important to scientific reproducibility, were more aware of proper RDM, had higher RDM strength in their laboratories and were more compliant with the DMP. Both research PIs and researchers believed data auditing helped them to be more compliant with data deposition in the repository. However, data auditing had no significant impact on laboratories’ data deposition rates over time, which could be due to the short sampling period.

Conclusions

Research PIs and researchers generally felt that data auditing was effective in improving RDM practices. It helped to evaluate their RDM practices objectively, propose corrective actions for RDM lapses and spread awareness of the university’s data management policies. Our findings corroborated other studies in medical research, geosciences, engineering and ethics that data auditing promotes good RDM practices. Hence, we recommend research institutions worldwide to adopt data auditing as a tool to reinforce research integrity.
Motivation to participate and experiences of the informed consent process for randomized clinical trials in emergency obstetric care in Uganda
Authors: Kaye Dan Kabonge
Published: July 2021

Background

Informed consent, whose goal is to assure that participants enter research voluntarily after disclosure of potential risks and benefits, may be impossible or impractical in emergency research. In low resource settings, there is limited information on the experiences of the informed consent process for randomized clinical trials in the emergency care context. The objective of this study was to explore the experiences of the informed consent process and factors that motivated participation in two obstetrics and newborn care randomized clinical trials (RCTs).

Methods

This was a qualitative study conducted among former participants of RCTs in the emergency obstetric care context, conducted at Kawempe National Referral Hospital, Uganda. It employed 30 in-depth interviews conducted from June 1, 2019 to August 30, 2019. Issues explored included attitudes about research, the purpose of the research in which they participated, motivations to take part in the study, factors that influenced enrolment decisions, and experiences of the informed consent process.

Results

Respondents felt that research was necessary to investigate the cause, prevention or complications of illness. The decisions to participate were influenced by hope for material or therapeutic benefit, trust in the healthcare system and influence of friends and family members. Many were satisfied with the informed consent process, though they did not understand some aspects of the research.

Conclusion

Respondents valued participation in RCTs in emergency obstetric and newborn care. Hope for benefit, altruism, desire to further scientific knowledge and trust in the investigators featured prominently in the motivation to participate. Both intrinsic and extrinsic factors were motivators for RCT participation.
Caregiver reactions to neuroimaging evidence of covert consciousness in patients with severe brain injury: a qualitative interview study
Authors: Peterson Andrew , Webster Fiona , Gonzalez-Lara Laura Elizabeth , Munce Sarah , Owen Adrian M. , Weijer Charles
Published: July 2021

Background

Severe brain injury is a leading cause of death and disability. Diagnosis and prognostication are difficult, and errors occur often. Novel neuroimaging methods can improve diagnostic and prognostic accuracy, especially in patients with prolonged disorders of consciousness (PDoC). Yet it is currently unknown how family caregivers understand this information, raising ethical concerns that disclosure of neuroimaging results could result in therapeutic misconception or false hope.

Methods

To examine these ethical concerns, we conducted semi-structured interviews with caregivers of patients with PDoC who were enrolled in a concurrent neuroimaging research program designed to detect covert consciousness following severe brain injury. Caregivers held surrogate decision-making status for a patient. Interviews were conducted at two time points for each caregiver. The first interview occurred before the disclosure of neuroimaging results. The second occurred after disclosure. Descriptive analysis was applied to the data of four interview topics: (1) expectations for neuroimaging; (2) reactions to evidence of preserved cognition; (3) reactions to null results; and (4) understanding of the results and study.

Results

Twelve caregivers participated in the study; two caregivers shared surrogate decision-making status for one patient with PDoC. Twenty-one interviews were completed; one caregiver declined to participate in the post-disclosure interview. Three patients with PDoC associated with the study displayed evidence of covert consciousness. Overall, caregivers understood the neuroimaging research and results. Caregivers who received results of covert consciousness were generally pleased. However, there was some variation in expectations and reactions to these data and null results.

Conclusion

This study, for the first time, reveals caregiver expectations for and reactions to neuroimaging evidence of covert consciousness in patients with PDoC. Caregivers understood the neuroimaging research and results, casting doubt on speculative ethical concerns regarding therapeutic misconception and false hope. However, disclosure of neuroimaging result could be improved. Pre-disclosure consultations might assist professionals in shaping caregiver expectations. Standardization of disclosure might also improve comprehension of the results.
Parenteral artemisinins are associated with reduced mortality and neurologic deficits and improved long-term behavioral outcomes in children with severe malaria
Authors: Conroy Andrea L. , Opoka Robert O. , Bangirana Paul , Namazzi Ruth , Okullo Allen E. , Georgieff Michael K. , Cusick Sarah , Idro Richard , Ssenkusu John M. , John Chandy C.
Published: July 2021

Background

In 2011, the World Health Organization recommended injectable artesunate as the first-line therapy for severe malaria (SM) due to its superiority in reducing mortality compared to quinine. There are limited data on long-term clinical and neurobehavioral outcomes after artemisinin use for treatment of SM.

Methods

From 2008 to 2013, 502 Ugandan children with two common forms of SM, cerebral malaria and severe malarial anemia, were enrolled in a prospective observational study assessing long-term neurobehavioral and cognitive outcomes following SM. Children were evaluated a week after hospital discharge, and 6, 12, and 24 months of follow-up, and returned to hospital for any illness. In this study, we evaluated the impact of artemisinin derivatives on survival, post-discharge hospital readmission or death, and neurocognitive and behavioral outcomes over 2 years of follow-up.

Results

346 children received quinine and 156 received parenteral artemisinin therapy (artemether or artesunate). After adjustment for disease severity, artemisinin derivatives were associated with a 78% reduction in in-hospital mortality (adjusted odds ratio, 0.22; 95% CI, 0.07–0.67). Among cerebral malaria survivors, children treated with artemisinin derivatives also had reduced neurologic deficits at discharge (quinine, 41.7%; artemisinin derivatives, 23.7%, p=0.007). Over a 2-year follow-up, artemisinin derivatives as compared to quinine were associated with better adjusted scores (negative scores better) in internalizing behavior and executive function in children irrespective of the age at severe malaria episode. After adjusting for multiple comparisons, artemisinin derivatives were associated with better adjusted scores in behavior and executive function in children <6 years of age at severe malaria exposure following adjustment for child age, sex, socioeconomic status, enrichment in the home environment, and the incidence of hospitalizations over follow-up. Children receiving artesunate had the greatest reduction in mortality and benefit in behavioral outcomes and had reduced inflammation at 1-month follow-up compared to children treated with quinine.

Conclusions

Treatment of severe malaria with artemisinin derivatives, particularly artesunate, results in reduced in-hospital mortality and neurologic deficits in children of all ages, reduced inflammation following recovery, and better long-term behavioral outcomes. These findings suggest artesunate has long-term beneficial effects in children surviving severe malaria.
Evaluation of the safety profile of COVID-19 vaccines: a rapid review
Authors: Wu Qianhui , Dudley Matthew Z. , Chen Xinghui , Bai Xufang , Dong Kaige , Zhuang Tingyu , Salmon Daniel , Yu Hongjie
Published: July 2021

Background

The rapid process of research and development and lack of follow-up time post-vaccination aroused great public concern about the safety profile of COVID-19 vaccine candidates. To provide comprehensive overview of the safety profile of COVID-19 vaccines by using meta-analysis technique.

Methods

English-language articles and results posted on PubMed, Embase, Web of Science, PMC, official regulatory websites, and post-authorization safety surveillance data were searched through June 12, 2021. Publications disclosing safety data of COVID-19 candidate vaccines in humans were included. A meta-analysis of proportions was performed to estimate the pooled incidence and the pooled rate ratio (RR) of safety outcomes of COVID-19 vaccines using different platforms.

Results

A total of 87 publications with safety data from clinical trials and post-authorization studies of 19 COVID-19 vaccines on 6 different platforms were included. The pooled rates of local and systemic reactions were significantly lower among inactivated vaccines (23.7%, 21.0%), protein subunit vaccines (33.0%, 22.3%), and DNA vaccines (39.5%, 29.3%), compared to RNA vaccines (89.4%, 83.3%), non-replicating vector vaccines (55.9%, 66.3%), and virus-like particle vaccines (100.0%, 78.9%). Solicited injection-site pain was the most common local reactions, and fatigue and headache were the most common systemic reactions. The frequency of vaccine-related serious adverse events was low (< 0.1%) and balanced between treatment groups. Vaccine platforms and age groups of vaccine recipients accounted for much of the heterogeneity in safety profiles between COVID-19 vaccines. Reporting rates of adverse events from post-authorization observational studies were similar to results from clinical trials. Crude reporting rates of adverse events from post-authorization safety monitoring (passive surveillance) were lower than in clinical trials and varied between countries.

Conclusions

Available evidence indicates that eligible COVID-19 vaccines have an acceptable short-term safety profile. Additional studies and long-term population-level surveillance are strongly encouraged to further define the safety profile of COVID-19 vaccines.
FGF21/adiponectin ratio predicts deterioration in glycemia: a 4.6-year prospective study in China
Authors: Liu Dan , Wu Liang , Gao Qiongmei , Long Xiaoxue , Hou Xuhong , Qian Lingling , Ni Jiacheng , Fang Qichen , Li Huating , Jia Weiping
Published: July 2021

Background

The fibroblast growth factor (FGF) 21-adiponectin pathway is involved in the regulation of insulin resistance. However, the relationship between the FGF21-adiponectin pathway and type 2 diabetes in humans is unclear. Here, we investigated the association of FGF21/adiponectin ratio with deterioration in glycemia in a prospective cohort study.

Methods

We studied 6361 subjects recruited from the prospective Shanghai Nicheng Cohort Study in China. The association between baseline FGF21/adiponectin ratio and new-onset diabetes and incident prediabetes was evaluated using multiple logistic regression analysis.

Results

At baseline, FGF21/adiponectin ratio levels increased progressively with the deterioration in glycemic control from normal glucose tolerance to prediabetes and diabetes (p for trend < 0.001). Over a median follow-up of 4.6 years, 195 subjects developed new-onset diabetes and 351 subjects developed incident prediabetes. Elevated baseline FGF21/adiponectin ratio was a significant predictor of new-onset diabetes independent of traditional risk factors, especially in subjects with prediabetes (odds ratio, 1.367; p = 0.001). Moreover, FGF21/adiponectin ratio predicted incident prediabetes (odds ratio, 1.185; p = 0.021) while neither FGF21 nor adiponectin were independent predictors of incident prediabetes (both p > 0.05). Furthermore, net reclassification improvement and integrated discrimination improvement analyses showed that FGF21/adiponectin ratio provided a better performance in diabetes risk prediction than the use of FGF21 or adiponectin alone.

Conclusions

FGF21/adiponectin ratio independently predicted the onset of prediabetes and diabetes, with the potential to be a useful biomarker of deterioration in glycemia.
Socioeconomic determinants and inequalities in the prevalence of non-communicable diseases in Saudi Arabia
Authors: Al-Hanawi Mohammed Khaled
Published: July 2021

Background

Non-communicable diseases (NCDs) are increasingly becoming a challenge worldwide, causing high mortality and morbidity. Saudi Arabia has one of the highest rates of NCDs globally and the highest in the Arabian Gulf region. Epidemiological data indicate that NCDs are responsible for 70 % of all deaths in Saudi Arabia. The aim of this study was to examine the socioeconomic determinants and inequalities in the prevalence of NCDs in Saudi Arabia.

Methods

Data from the Saudi Family Health Survey conducted in 2018 by the General Authority for Statistics were used for this study. Univariate, bivariate, and multivariate logistic regression analyses were employed to examine the socioeconomic factors associated with the prevalence of NCDs. Moreover, the concentration curve and concentration indices were used to assess inequalities in the prevalence of NCDs.

Results

Among the 11,527 respondents, the prevalence of NCDs was 32.15 %. The prevalence of NCDs was higher among women and among elderly respondents aged ≥ 60 years. With respect to the determinants of the prevalence of NCDs, the logistic regression results showed that the likelihood of reporting NCDs was lower among people with a higher education (OR: 0.599, 95 % CI: 0.497–0.723,p < 0.01) compared with that of people with an education below the primary school level. Other factors significantly associated with the prevalence of NCDs were age, marital status, nationality, and region of residence. The inequality analysis showed that at the national level, the prevalence of NCDs was concentrated among less educated people (concentration index = − 0.338,p < 0.01), but with significant regional variations. Gender disaggregation showed that both income-based and education-based concentration indices were significantly negative among women, indicating that the prevalence of NCDs is concentrated among women with a lower income level and with less education.

Conclusions

The findings of this study are important for policymakers to combat both the increasing prevalence of and socio-economic inequalities in NCDs. The government should develop targeted intervention strategies to control NCDs and achieve health equality considering socio-economic status. Future policies should target women and the lower educated population in Saudi Arabia.
Exploring factors affecting individual GPS-based activity space and how researcher-defined food environments represent activity space, exposure and use of food outlets
Authors: Marwa Windi Lameck , Radley Duncan , Davis Samantha , McKenna James , Griffiths Claire
Published: July 2021

Background

Obesity remains one of the most challenging public health issues of our modern time. Despite the face validity of claims for influence, studies on the causes of obesity have reported the influence of the food environment to be inconsistent. This inconsistency has been attributed to the variability of measures used by researchers to represent the food environments—Researcher-Defined Food Environments (RDFE) like circular, street-network buffers, and others. This study (i.) determined an individual’s Activity Space (AS) (ii.) explored the accuracy of the RDFE in representing the AS, (iii.) investigated the accuracy of the RDFE in representing actual exposure, and (iv.) explored whether exposure to food outlet reflects the use of food outlets.

Methods

Data were collected between June and December 2018. A total of 65 participants collected Global Positioning System (GPS) data, kept receipt of all their food purchases, completed a questionnaire about their personal information and had their weight and height measured. A buffer was created around the GPS points and merged to form an AS (GPS-based AS).

Results

Statistical and geospatial analyses found that the AS size of participants working away from home was positively related to the Euclidean distance from home to workplace; the orientation (shape) of AS was also influenced by the direction of workplace from home and individual characteristics were not predictive of the size of AS. Consistent with some previous studies, all types and sizes of RDFE variably misrepresented individual exposure in the food environments. Importantly, the accuracy of the RDFE was significantly improved by including both the home and workplace domains. The study also found no correlation between exposure and use of food outlets.

Conclusions

Home and workplace are key activity nodes in modelling AS or food environments and the relationship between exposure and use is more complex than is currently suggested in both empirical and policy literature.
Long-term cold storage preservation does not affect fatty livers from rats fed with a methionine and choline deficient diet
Authors: Di Pasqua Laura Giuseppina , Berardo Clarissa , Cagna Marta , Mannucci Barbara , Milanesi Gloria , Croce Anna Cleta , Ferrigno Andrea , Vairetti Mariapia
Published: July 2021

Background

Waiting lists that continue to grow and the lack of organs available for transplantation necessitate the use of marginal livers, such as fatty livers. Since steatotic livers are more susceptible to damage from ischemia and reperfusion, it was investigated whether fatty livers with different lipidomic profiles show a different outcome when subjected to long-term cold storage preservation.

Methods

Eight-week-old male Wistar rats fed for 2 weeks by a methionine-choline-deficient (MCD) diet or control diet were employed in this study. Livers were preserved in a University of Wisconsin (UW) solution at 4 °C for 6, 12 or 24 h and, after washout, reperfused for 2 h with a Krebs-Henseleit buffer at 37 °C. Hepatic enzyme release, bile production, O2-uptake, and portal venous pressure (PVP) were evaluated. The liver fatty acid profile was evaluated by a gas chromatography-mass spectrometry (GC/MS).

Results

MCD rats showed higher LDH and AST levels with respect to the control group. When comparing MCD livers preserved for 6, 12 or 24 h, no differences in enzyme release were found during both the washout or the reperfusion period. The same trend occurred for O2-uptake, PVP, and bile flow. A general decrease in SFA and MUFA, except for oleic acid, and a decrease in PUFA, except for arachidonic, eicosadienoic, and docosahexanaeoic acids, were found in MCD rats when compared with control rats. Moreover, the ratio between SFA and the various types of unsaturated fatty acids (UFA) was significantly lower in MCD rats.

Conclusions

Although prolonged cold ischemia negatively affects the graft outcome, our data suggest that the quality of lipid constituents could influence liver injury during cold storage: the lack of an increased hepatic injury in MCD may be justified by low SFA, which likely reduces the deleterious tendency toward lipid crystallization occurring under cold ischemia.
Usefulness of the triglyceride glucose-body mass index in evaluating nonalcoholic fatty liver disease: insights from a general population
Authors: Wang Rongsheng , DAI Longlong , Zhong Yanjia , Xie Guobo
Published: July 2021

Background

Triglyceride glucose-body mass index (TyG-BMI) is a recently developed alternative indicator to identify insulin resistance. However, few studies have investigated the association between the TyG-BMI and nonalcoholic fatty liver disease (NAFLD). Therefore, this study aimed to study the relationship between NAFLD and the TyG-BMI in the general population and its predictive value.

Methods

A cross-sectional study was conducted on 14,251 general subjects who took part in a comprehensive health examination. The anthropological characteristics and many risk factors for NAFLD were measured.

Results

After fully adjusting for confounding variables, a stable positive correlation was found between NAFLD and the TyG-BMI (OR: 3.90 per SD increase; 95% CI: 3.54 to 4.29; P-trend< 0.00001). This positive correlation was not simply linear but a stable non-linear correlation. Additionally, obvious threshold effects and saturation effects were found, in which a threshold effect occurred when the TyG-BMI was between 100 and 150; when the TyG-BMI was between 300 and 400, the corresponding NAFLD risk appeared saturated. Furthermore, receiver operating characteristic analysis showed that the TyG-BMI could better predict the risk of NAFLD than other traditional indicators [TyG-BMI (AUC): 0.886; 95% CI: 0.8797–0.8927; P < 0.0001], particularly among young and middle-aged and non-obese people.

Conclusions

This epidemiological study is the first on the association between the TyG-BMI and NAFLD risk in the general population. In this large data set from the general population, the TyG-BMI showed an independent positive correlation with NAFLD. The discovery of the threshold effect and saturation effect between them provides a new idea to prevent and treat NAFLD.