bluuebunny/crossref_metadata_2025 huggingface dataset:
Socioeconomic and behavioural factors associated with access to and use of Personal Health Records
Authors: Paccoud Ivana , Baumann Michèle , Le Bihan Etienne , Pétré Benoît , Breinbauer Mareike , Böhme Philip , Chauvel Louis , Leist Anja K.
Published: January 2021

Background

Access to and use of digital technology are more common among people of more advantaged socioeconomic status. These differences might be due to lack of interest, not having physical access or having lower intentions to use this technology. By integrating the digital divide approach and the User Acceptance of Information Technology (UTAUT) model, this study aims to further our understanding of socioeconomic factors and the mechanisms linked to different stages in the use of Personal Health Records (PHR): desire, intentions and physical access to PHR.

Methods

A cross-sectional online and in-person survey was undertaken in the areas of Lorraine (France), Luxembourg, Rhineland-Palatinate and Saarland (Germany), and Wallonia (Belgium). Exploratory factor analysis was performed to group items derived from the UTAUT model. We applied linear and logistic regressions controlling for country-level heterogeneity, health and demographic factors.

Results

A total of 829 individuals aged over 18 completed the questionnaire. Socioeconomic inequalities were present in the access to and use of PHR. Education and income played a significant role in individuals' desire to access their PHR. Being older than 65 years, and migrant, were negatively associated with desire to access PHR. An income gradient was found in having physical access to PHR, while for the subgroup of respondents who expressed desire to have access, higher educational level was positively associated with intentions to regularly use PHR. In fully adjusted models testing the contribution of UTAUT-derived factors, individuals who perceived PHRs to be useful and had the necessary digital skills were more inclined to use their PHR regularly. Social influence, support and lack of anxiety in using technology were strong predictors of regular PHR use.

Conclusion

The findings highlight the importance of considering all stages in PHR use: desire to access, physical access and intention to regularly use PHRs, while paying special attention to migrants and people with less advantaged socioeconomic backgrounds who may feel financial constraints and are not able to exploit the potential of PHRs. As PHR use is expected to come with health benefits, facilitating access and regular use for those less inclined could reduce health inequalities and advance health equity.
Evaluation of a delirium awareness podcast for undergraduate nursing students in Northern Ireland: a pre−/post-test study
Authors: Mitchell Gary , Scott Jessica , Carter Gillian , Wilson Christine Brown
Published: January 2021

Background

Delirium is a common disorder affecting several people in primary, secondary, and tertiary settings. The condition is frequently under-diagnosed leading to long-lasting physical and cognitive impairment or premature death. Despite this, there has been limited research on the impact of innovative approaches to delirium education amongst undergraduate nursing students. The aim of this study was to evaluate the effect of a delirium awareness podcast on undergraduate nursing student knowledge and confidence related to the condition in Northern Ireland.

Methods

The intervention was a 60-min delirium awareness podcast, available throughout May 2020, to a convenience sample of year one undergraduate nursing students (n = 320) completing a BSc Honours Nursing degree programme in a Northern Ireland University. The podcast focused on how nursing students could effectively recognise, manage, and prevent delirium. Participants had a period of 4 weeks to listen to the podcast and complete the pre and post questionnaires. The questionnaires were comprised of a 35-item true-false Delirium Knowledge Questionnaire (DKQ), a 3-item questionnaire about professional confidence and a 7-item questionnaire evaluating the use of podcasting as an approach to promote knowledge and confidence about delirium. Data were analysed using paired t-tests and descriptive statistics.

Results

Students improved across all three core areas in the post-test questionnaire, demonstrating improvements in knowledge about symptoms of delirium (7.78% increase), causes and risk factors of delirium (13.34% increase) and management of delirium (12.81% increase). In relation to perceived confidence, students reported a 46.50% increase in confidence related to recognition of delirium, a 48.32% increase in relation to delirium management and a 50.71% increase their ability to communicate about delirium. Both questionnaires were statistically significant (P < 0.001). The final questionnaire illustrated that nursing students positively evaluated the use of podcast for promoting their knowledge and confidence about delirium and 96.32% of nursing students believed that the podcast met their learning needs about delirium.

Conclusions

A 60-min podcast on delirium improved first year student nurse knowledge about delirium. Nursing students also expressed that this approach to delirium education was effective in their learning about the condition.
Assessment of local supply chains and stock management practices for trauma care resources in Ghana: a comparative small sample cross-sectional study
Authors: Boakye Godfred , Gyedu Adam , Stewart Melissa , Donkor Peter , Mock Charles , Stewart Barclay
Published: January 2021

Background

Injuries are a major public health problem globally. With sound planning and organization, essential trauma care can be reliably provided with relatively low-cost equipment and supplies. However, availability of these resources requires an effective and efficient supply chain and good stock management practices. Therefore, this study aimed to assess trauma care resource-related supply management structures and processes at health facilities in Ghana. By doing so, the findings may allow us to identify specific structures and processes that could be improved to facilitate higher quality and more timely care.

Methods

Ten hospitals were purposively selected using results from a previously performed national trauma care capacity assessment of hospitals of all levels in Ghana. Five hospitals with low resource availability and 5 hospitals with high resource availability were assessed using the United States Agency for International Development (USAID) Logistics Indicators Assessment Tool and stock ledger review. Data were described and stock management practices were correlated with resource availability.

Results

There were differences in stock management practices between low and high resource availability hospitals, including frequency of reporting and audit, number of stock-outs on day of assessment (median 9 vs 2 stock-outs, range 3–57 vs 0–9 stock-outs, respectively; p = 0.05), duration of stock-outs (median 171 vs 8 days, range 51–1268 vs 0–182 days, respectively; p = 0.02), and fewer of up-to-date stock cards (24 vs 31 up-to-date stock cards, respectively; p = 0.07). Stock-outs were common even among low-cost, essential resources (e.g., nasal cannulas and oxygen masks, endotracheal tubes, syringes, sutures, sterile gloves). Increased adherence to stock management guidelines and higher percentage of up-to-date stock cards were correlated with higher trauma resource availability scores. However, the variance in trauma resource availability scores was poorly explained by these individual factors or when analyzed in a multivariate regression model (r2 = 0.72; p value for each covariate between 0.17–0.34).

Conclusions

Good supply chain and stock management practices are correlated with high trauma care resource availability. The findings from this study demonstrate several opportunities to improve stock management practices, particularly at low resource availability hospitals.
Non-genetic risk and protective factors and biomarkers for neurological disorders: a meta-umbrella systematic review of umbrella reviews
Authors: Mentis Alexios-Fotios A. , Dardiotis Efthimios , Efthymiou Vasiliki , Chrousos George P.
Published: January 2021

Background

The etiologies of chronic neurological diseases, which heavily contribute to global disease burden, remain far from elucidated. Despite available umbrella reviews on single contributing factors or diseases, no study has systematically captured non-purely genetic risk and/or protective factors for chronic neurological diseases.

Methods

We performed a systematic analysis of umbrella reviews (meta-umbrella) published until September 20th, 2018, using broad search terms in MEDLINE, SCOPUS, Web of Science, Cochrane Database of Systematic Reviews, Cumulative Index to Nursing and Allied Health Literature, ProQuest Dissertations & Theses, JBI Database of Systematic Reviews and Implementation Reports, DARE, and PROSPERO. The PRISMA guidelines were followed for this study. Reference lists of the identified umbrella reviews were also screened, and the methodological details were assessed using the AMSTAR tool. For each non-purely genetic factor association, random effects summary effect size, 95% confidence and prediction intervals, and significance and heterogeneity levels facilitated the assessment of the credibility of the epidemiological evidence identified.

Results

We identified 2797 potentially relevant reviews, and 14 umbrella reviews (203 unique meta-analyses) were eligible. The median number of primary studies per meta-analysis was 7 (interquartile range (IQR) 7) and that of participants was 8873 (IQR 36,394). The search yielded 115 distinctly named non-genetic risk and protective factors with a significant association, with various strengths of evidence. Mediterranean diet was associated with lower risk of dementia, Alzheimer disease (AD), cognitive impairment, stroke, and neurodegenerative diseases in general. In Parkinson disease (PD) and AD/dementia, coffee consumption, and physical activity were protective factors. Low serum uric acid levels were associated with increased risk of PD. Smoking was associated with elevated risk of multiple sclerosis and dementia but lower risk of PD, while hypertension was associated with lower risk of PD but higher risk of dementia. Chronic occupational exposure to lead was associated with higher risk of amyotrophic lateral sclerosis. Late-life depression was associated with higher risk of AD and any form of dementia.

Conclusions

We identified several non-genetic risk and protective factors for various neurological diseases relevant to preventive clinical neurology, health policy, and lifestyle counseling. Our findings could offer new perspectives in secondary research (meta-research).
The elastin peptide VGVAPG increases CD4+ T-cell IL-4 production in patients with chronic obstructive pulmonary disease
Authors: Lemaire Flora , Audonnet Sandra , Perotin Jeanne-Marie , Gaudry Pierre , Dury Sandra , Ancel Julien , Lebargy François , Antonicelli Frank , Deslée Gaëtan , Le Naour Richard
Published: January 2021

Background

In chronic obstructive pulmonary disease (COPD), lung-infiltrating inflammatory cells secrete proteases and participate in elastin breakdown and genesis of elastin-derived peptides (EP). In the present study, we hypothesized that the pattern of T lymphocytes cytokine expression may be modulated by EP in COPD patients.

Methods

CD4+ and CD8+ T-cells, sorted from peripheral blood mononuclear cells (PBMC) collected from COPD patients (n = 29) and controls (n = 13) were cultured with or without EP. Cytokine expression in T-cell phenotypes was analyzed by multicolor flow cytometry, whereas desmosine concentration, a specific marker of elastin degradation, was measured in sera.

Results

Compared with control, the percentage of IL-4 (Th2) producing CD4+ T-cells was decreased in COPD patients (35.3 ± 3.4% and 26.3 ± 2.4%, respectively, p < 0.05), whereas no significant differences were found with IFN-γ (Th1) and IL-17A (Th17). Among COPD patients, two subpopulations were observed based on the percentage of IL-4 (Th2) producing CD4+ T-cells, of which only one expressed high IL-4 levels in association with high levels of desmosine and strong smoking exposure (n = 7). Upon stimulation with VGVAPG, a bioactive EP motif, the percentage of CD4+ T cells expressing IL-4 significantly increased in COPD patients (p < 0.05), but not in controls. The VGVAPG-induced increase in IL-4 was inhibited in the presence of analogous peptide antagonizing VGVAPG/elastin receptor (S-gal) interactions.

Conclusions

The present study demonstrates that the VGVAPG elastin peptide modulates CD4+ T-cells IL-4 production in COPD. Monitoring IL-4 in circulating CD4+ T-cells may help to better characterize COPD phenotypes and could open a new pharmacologic opportunity through CD4+ T-cells stimulation via the VGVAPG/S-gal receptor in order to favor an anti-inflammatory response in those COPD patients.
Allelic diversity of MSP1 and MSP2 repeat loci correlate with levels of malaria endemicity in Senegal and Nigerian populations
Authors: Oboh Mary A. , Ndiaye Tolla , Diongue Khadim , Ndiaye Yaye D. , Sy Mouhamad , Deme Awa B. , Diallo Mamadou A. , Yade Mamadou S. , Volkman Sarah K. , Badiane Aida S. , Amambua-Ngwa Alfred , Ndiaye Daouda
Published: January 2021

Background

Characterizing the genetic diversity of malaria parasite populations in different endemic settings (from low to high) could be helpful in determining the effectiveness of malaria interventions. This study comparedPlasmodium falciparumparasite population diversity from two sites with low (pre-elimination) and high transmission in Senegal and Nigeria, respectively.

Methods

Parasite genomic DNA was extracted from 187 dried blood spot collected from confirmed uncomplicatedP. falciparummalaria infected patients in Senegal (94) and Nigeria (93). Allelic polymorphism atmerozoite surface protein1 (msp1) andmerozoite surface protein- 2 (msp2) genes were assessed by nested PCR.

Results

The most frequentmsp1andmsp2allelic families are the K1 and IC3D7 allelotypes in both Senegal and Nigeria. Multiplicity of infection (MOI) of greater that 1 and thus complex infections was common in both study sites in Senegal (Thies:1.51/2.53; Kedougou:2.2/2.0 formsp1/2) than in Nigeria (Gbagada: 1.39/1.96; Oredo: 1.35/1.75]). The heterozygosity ofmsp1gene was higher inP. falciparumisolates from Senegal (Thies: 0.62; Kedougou: 0.53) than isolates from Nigeria (Gbagada: 0.55; Oredo: 0.50). In Senegal, K1 alleles was associated with heavy than with moderate parasite density. Meanwhile, equal proportions of K1 were observed in both heavy and moderate infection types in Nigeria. The IC3D7 subtype allele of themsp2family was the most frequent in heavily parasitaemic individuals from both countries than in the moderately infected participants.

Conclusion

The unexpectedly low genetic diversity of infections high endemic Nigerian setting compared to the low endemic settings in Senegal is suggestive of possible epidemic outbreak in Nigeria.
A comparative evaluation of mobile medical APPS (MMAS) for reading and interpreting malaria rapid diagnostic tests
Authors: Visser Theodoor , Ramachandra Sumedh , Pothin Emilie , Jacobs Jan , Cunningham Jane , Menach Arnaud Le , Gatton Michelle L. , dos Santos Souza Samaly , Nelson Sydney , Rooney Luke , Aidoo Michael
Published: January 2021

Background

The World Health Organization recommends confirmatory diagnosis by microscopy or malaria rapid diagnostic test (RDT) in patients with suspected malaria. In recent years, mobile medical applications (MMAs), which can interpret RDT test results have entered the market. To evaluate the performance of commercially available MMAs, an evaluation was conducted by comparing RDT results read by MMAs to RDT results read by the human eye.

Methods

Five different MMAs were evaluated on six different RDT products using cultured Plasmodium falciparum blood samples at five dilutions ranging from 20 to 1000 parasites (p)/microlitre (µl) and malaria negative blood samples. The RDTs were performed in a controlled, laboratory setting by a trained operator who visually read the RDT results. A second trained operator then used the MMAs to read the RDT results. Sensitivity (Sn) and specificity (Sp) for the RDTs were calculated in a Bayesian framework using mixed models.

Results

The RDT Sn of the P. falciparum (Pf) test line, when read by the trained human eye was significantly higher compared to when read by MMAs (74% vs. average 47%) at samples of 20 p/µl. In higher density samples, the Sn was comparable to the human eye (97%) for three MMAs. The RDT Sn of test lines that detect all Plasmodium species (Pan line), when read by the trained human eye was significantly higher compared to when read by MMAs (79% vs. average 56%) across all densities. The RDT Sp, when read by the human eye or MMAs was 99% for both the Pf and Pan test lines across all densities.

Conclusions

The study results show that in a laboratory setting, most MMAs produced similar results interpreting the Pf test line of RDTs at parasite densities typically found in patients that experience malaria symptoms (> 100 p/µl) compared to the human eye. At low parasite densities for the Pf line and across all parasite densities for the Pan line, MMAs were less accurate than the human eye. Future efforts should focus on improving the band/line detection at lower band intensities and evaluating additional MMA functionalities like the ability to identify and classify RDT errors or anomalies.
Effectiveness of the school-based social and behaviour change communication interventions on insecticide-treated nets utilization among primary school children in rural Ethiopia: a controlled quasi-experimental design
Authors: Abamecha Fira , Sudhakar Morankar , Abebe Lakew , Kebede Yohannes , Alemayehu Guda , Birhanu Zewdie
Published: January 2021

Background

School-based behaviour change communication interventions could help to achieve behavioural changes in the school and enhance the enrollment of the students and teachers as health messengers to local communities. Evidence on the impacts of the school-engaged malaria preventive interventions are limited as far as the social and behaviour change communication (SBCC) is concerned. This study examined the effectiveness of the school-based SBCC approach on insecticide-treated nets (ITNs) utilization among primary school students in malaria-endemic settings of Ethiopia.

Methods

Various participatory, educational, and communication interventions were implemented from 2017 to 2019 in 75 primary schools and respective villages in Jimma to promote malaria preventive practices. A quasi-experimental design was conducted with randomly selected 798 students (i.e. 399 intervention and 399 control groups). Data were collected by trained interviewers using structured questionnaires. The SPSS version 26 software was used to analyse the data. Propensity score matching analysis was performed to control for possible confounding biases. The average effects of the intervention were estimated using multivariate general linear modelling to estimate for mean differences and odds ratio based on the nature of data.

Results

The result showed that the ITNs utilization was 6.857 folds in the intervention groups compared to the counterpart; (OR = 6.857; 95% CI: (4.636, 10.1430); effect size = 39%). A mean differences (MD) of self-efficacy (MD = 15.34; 95% CI: 13.73 to 16.95), knowledge (MD = 5.83; 95% CI: 5.12 to 6.55), attitude (MD = 6.01; 95% CI: 5.26 to 6.77), perceived malaria risk (MD = 2.14; 95% CI: 1.53 to 2.76), and perceived family supports (MD = 6.39; 95% CI: 5.57 to 7.22) were observed favoring the intervention. Multivariable logistic regression modelling results showed that knowledge (β = 0.194, 95% CI: 1.09 to 1.35) and perceived family supports (β = 0.165, 95% CI: 1.11 to 1.25) and self-efficacy (β = 0.10, 95% CI: 1.22 to 2.32) predicted the ITN utilization among the school children.

Conclusions

The finding of this study suggested that the school-based SBCC approach combined with peer education activities advanced the malaria-related knowledge, attitude, self-efficacy, risk perceptions, and family supports and ultimately improved the sustained use of ITNs among school-going children. Further research should be conducted to understand the mechanism of these effects given the influences of social, health services, and school systems are considered.
Relationships between test positivity rate, total laboratory confirmed cases of malaria, and malaria incidence in high burden settings of Uganda: an ecological analysis
Authors: Okiring Jaffer , Epstein Adrienne , Namuganga Jane F. , Kamya Victor , Sserwanga Asadu , Kapisi James , Ebong Chris , Kigozi Simon P. , Mpimbaza Arthur , Wanzira Humphrey , Briggs Jessica , Kamya Moses R. , Nankabirwa Joaniter I. , Dorsey Grant
Published: January 2021

Background

Malaria surveillance is critical for monitoring changes in malaria morbidity over time. National Malaria Control Programmes often rely on surrogate measures of malaria incidence, including the test positivity rate (TPR) and total laboratory confirmed cases of malaria (TCM), to monitor trends in malaria morbidity. However, there are limited data on the accuracy of TPR and TCM for predicting temporal changes in malaria incidence, especially in high burden settings.

Methods

This study leveraged data from 5 malaria reference centres (MRCs) located in high burden settings over a 15-month period from November 2018 through January 2020 as part of an enhanced health facility-based surveillance system established in Uganda. Individual level data were collected from all outpatients including demographics, laboratory test results, and village of residence. Estimates of malaria incidence were derived from catchment areas around the MRCs. Temporal relationships between monthly aggregate measures of TPR and TCM relative to estimates of malaria incidence were examined using linear and exponential regression models.

Results

A total of 149,739 outpatient visits to the 5 MRCs were recorded. Overall, malaria was suspected in 73.4% of visits, 99.1% of patients with suspected malaria received a diagnostic test, and 69.7% of those tested for malaria were positive. Temporal correlations between monthly measures of TPR and malaria incidence using linear and exponential regression models were relatively poor, with small changes in TPR frequently associated with large changes in malaria incidence. Linear regression models of temporal changes in TCM provided the most parsimonious and accurate predictor of changes in malaria incidence, with adjusted R2 values ranging from 0.81 to 0.98 across the 5 MRCs. However, the slope of the regression lines indicating the change in malaria incidence per unit change in TCM varied from 0.57 to 2.13 across the 5 MRCs, and when combining data across all 5 sites, the R2 value reduced to 0.38.

Conclusions

In high malaria burden areas of Uganda, site-specific temporal changes in TCM had a strong linear relationship with malaria incidence and were a more useful metric than TPR. However, caution should be taken when comparing changes in TCM across sites.
Instructive roles and supportive relationships: client perspectives of their engagement with community health workers in a rural South African home visiting program
Authors: Laurenzi Christina A. , Skeen Sarah , Coetzee Bronwynè J. , Notholi Vuyolwethu , Gordon Sarah , Chademana Emma , Bishop Julia , Tomlinson Mark
Published: January 2021

Background

Community health worker (CHW) programs have been positioned as a way to meet the needs of those who experience marginalization and inequitable access to health care, and current global health narratives also emphasize their adaptable nature to meet growing health burdens in low-income settings. However, as CHW programs adopt more technical roles, the value of CHWs in building relationships with clients tends to be overlooked. More importantly, these programs are often reframed and redeployed without attending to the interests and needs of program clients themselves. We set out to gather perspectives of program and CHW engagement from clients of a maternal and child health program in rural South Africa.

Methods

We conducted 26 interviews with pregnant or recently-delivered clients of the Enable Mentor Mother program between February–March 2018. After obtaining informed consent, a trained research assistant conducted all interviews in the clients’ home language, isiXhosa. Interviews, translated and transcribed into English, were organized and coded using ATLAS.ti software and thematically analyzed.

Results

We found that clients’ home-based interactions with Mentor Mothers were generally positive, and that these engagements were characterized by two core themes, instructive roles and supportive relationships.. Instructive roles facilitated the transfer of knowledge and uptake of new information for behavior change. Relationships were developed within the home visit setting, but also extended beyond routine visits, especially when clients required further instrumental support. Clients further discussed a sense of agency gained through these interactions, even in cases where they chose not to, or were unable to, heed their Mentor Mother’s advice.

Conclusions

These findings highlight the important roles that CHWs can assume in providing both instructive and supportive care to clients; as deepening relationships may be key for encouraging behavior change, these findings pinpoint the need to bolster training and support for CHWs in similar programs. They also emphasize the importance of integrating more channels for client feedback into existing programs, to ensure that clients’ voices are heard and accounted for in shaping ongoing engagement within the communities in which these programs operate.
Macrophage function in the elderly and impact on injury repair and cancer
Authors: Duong L , Radley HG , Lee B , Dye DE , Pixley FJ , Grounds MD , Nelson DJ , Jackaman C
Published: January 2021

Older age is associated with deteriorating health, including escalating risk of diseases such as cancer, and a diminished ability to repair following injury. This rise in age-related diseases/co-morbidities is associated with changes to immune function, including in myeloid cells, and is related to immunosenescence. Immunosenescence reflects age-related changes associated with immune dysfunction and is accompanied by low-grade chronic inflammation or inflammageing. This is characterised by increased levels of circulating pro-inflammatory cytokines such as tumor necrosis factor (TNF), interleukin (IL)-1β and IL-6. However, in healthy ageing, there is a concomitant age-related escalation in anti-inflammatory cytokines such as transforming growth factor-β1 (TGF-β1) and IL-10, which may overcompensate to regulate the pro-inflammatory state. Key inflammatory cells, macrophages, play a role in cancer development and injury repair in young hosts, and we propose that their role in ageing in these scenarios may be more profound. Imbalanced pro- and anti-inflammatory factors during ageing may also have a significant influence on macrophage function and further impact the severity of age-related diseases in which macrophages are known to play a key role. In this brief review we summarise studies describing changes to inflammatory function of macrophages (from various tissues and across sexes) during healthy ageing. We also describe age-related diseases/co-morbidities where macrophages are known to play a key role, focussed on injury repair processes and cancer, plus comment briefly on strategies to correct for these age-related changes.
Cognitive and motor deficits contribute to longer braking time in stroke
Authors: Lodha Neha , Patel Prakruti , Shad Joanna M. , Casamento-Moran Agostina , Christou Evangelos A.
Published: January 2021

Background

Braking is a critical determinant of safe driving that depends on the integrity of cognitive and motor processes. Following stroke, both cognitive and motor capabilities are impaired to varying degrees. The current study examines the combined impact of cognitive and motor impairments on braking time in chronic stroke.

Methods

Twenty stroke survivors and 20 aged-matched healthy controls performed cognitive, motor, and simulator driving assessments. Cognitive abilities were assessed with processing speed, divided attention, and selective attention. Motor abilities were assessed with maximum voluntary contraction (MVC) and motor accuracy of the paretic ankle. Driving performance was examined with the braking time in a driving simulator and self-reported driving behavior.

Results

Braking time was 16% longer in the stroke group compared with the control group. The self-reported driving behavior in stroke group was correlated with braking time (r = − 0.53, p = 0.02). The stroke group required significantly longer time for divided and selective attention tasks and showed significant decrease in motor accuracy. Together, selective attention time and motor accuracy contributed to braking time (R2 = 0.40, p = 0.01) in stroke survivors.

Conclusions

This study provides novel evidence that decline in selective attention and motor accuracy together contribute to slowed braking in stroke survivors. Driving rehabilitation after stroke may benefit from the assessment and training of attentional and motor skills to improve braking during driving.
Study on suitable analysis method for HIV-1 non-catalytic integrase inhibitor
Authors: Park Ki Hoon , Kim Minjee , Bae Seoung Eun , Lee Hee Jung , Kim Kyung-Chang , Choi Byeong Sun , Kim Young Bong
Published: January 2021

Background

Integrase (IN) is an essential protein for HIV replication that catalyzes insertion of the reverse-transcribed viral genome into the host chromosome during the early steps of viral infection. Highly active anti-retroviral therapy is a HIV/AIDS treatment method that combines three or more antiviral drugs often formulated from compounds that inhibit the activities of viral reverse transcriptase and protease enzymes. Early IN inhibitors (INIs) mainly serve as integrase strand transfer inhibitors (INSTI) that disrupt strand transfer by binding the catalytic core domain of IN. However, mutations of IN can confer resistance to INSTI. Therefore, non-catalytic integrase inhibitors (NCINI) have been developed as next-generation INIs.

Methods

In this study, we evaluated and compared the activity of INSTI and NCINI according to the analysis method. Antiviral activity was compared using p24 ELISA with MT2 cell and TZM-bl luciferase system with TZM-bl cell. Each drug was serially diluted and treated to MT2 and TZM-b1 cells, infected with HIV-1 AD8 strain and incubated for 5 and 2 days, respectively. Additionally, to analyze properties of INSTI and NCINI, transfer inhibition assay and 3′-processing inhibition assay were performed.

Results

During screening of INIs using the p24 ELISA and TZM-bl luciferase systems, we found an inconsistent result with INSTI and NCINI drugs. Following infection of MT2 and TZM-bl cells with T-tropic HIV-1 strain, both INSTI and NCINI treatments induced significant p24 reduction in MT2 cells. However, NCINI showed no antiviral activity in the TZM-bl luciferase system, indicating that this widely used and convenient antiretroviral assay is not suitable for screening of NCINI compounds that target the second round of HIV-1 replication.

Conclusion

Accordingly, we recommend application of other assay procedures, such as p24 ELISA or reverse transcription activity, in lieu of the TZM-bl luciferase system for preliminary NCINI drug screening. Utilization of appropriate analytical methods based on underlying mechanisms is necessary for accurate assessment of drug efficacy.
Cross-sectional retrospective analysis of clinical characteristics of chronic hepatitis B patients with oral antiviral treatment in eastern China
Authors: Gu Jueqing , Yu Guodong , Zhang Xiaoli , Zhang Shanyan , Cai Huan , Ye Chanyuan , Yang Yida , Li Dezhou , Tong Zhaowei , Shen Huajiang , Chen Huazhong , Ding Feng , Lai Xijie , Liu Junyan , Xu Meiling , Wu Weiti
Published: January 2021

Background

In China, more than 20 million patients with chronic hepatitis B need antiviral treatment. Side effects of antiviral treatment such as renal complications can be problematic, particularly in an aging population.

Methods

The data were retrospectively extracted from the hospital medical charts of five centers in eastern China from January 1 to December 31, 2018.

Results

A total of 8309 patients with CHB was enrolled in this study. The median age of the patients was 46 years. The prevalence of diabetes mellitus, hypertension, and hepatic cirrhosis was respectively 3.49%, 4.42%, and 23.72%. The prevalence of these comorbidities increased with age (P < 0.001). Of the patients with CHB, 5332 had complete renal function results. Among them, patients with an estimated glomerular filtration rate of < 60 mL/min/1.73m2accounted for 4.14%, and those with proteinuria for 8.33%. According to the definition of chronic kidney disease, the proportion of patients with chronic kidney disease was 11.37%. The prevalence of chronic kidney disease increased with age (P < 0.001). In a multivariate analysis, age group [odds ratio (OR) = 2.387], diabetes mellitus (OR = 1.486), hypertension (OR = 2.557), hepatic cirrhosis (OR = 1.295), and a history of exposure to adefovir dipivoxil (OR = 1.644) were significantly associated with CKD (P < 0.05). Among patients with CKD, 17.66% (107/606) had a history of lamivudine exposure, and 34.65% (210/606) had a history of nucleotide analogue exposure

Conclusion

The management of Chinese patients with CHB should take into consideration age, previous medication history, and renal impairment.
Effect of individual- versus collective-based nutritional-lifestyle intervention on the atherogenic index of plasma in children with obesity: a randomized trial
Authors: Verduci Elvira , Banderali Giuseppe , Di Profio Elisabetta , Vizzuso Sara , Zuccotti Gianvincenzo , Radaelli Giovanni
Published: January 2021

Background

The Atherogenic Index of Plasma is a predictive biomarker of atherosclerosis in adults but there is a lack of studies in paediatric population aimed at evaluating the longitudinal changes of the AIP and of the cardiometabolic blood profile related to nutritional interventions. The aim of this study was to compare the effect of individual- versus collective-based nutritional-lifestyle intervention on the Atherogenic Index of Plasma in schoolchildren with obesity.

Methods

One-hundred sixty-four children aged 6–12 years with Body Mass Index z-score > 2 referred to the Paediatric Obesity Clinic, San Paolo Hospital, Milan, Italy, were consecutively enrolled and randomized to undergo to either an individual- (n = 82) or a collective- (n = 82) based intervention promoting a balanced normo-caloric diet and physical activity. In addition, the individual intervention included a tailored personalized nutritional advice and education based on the revised Coventry, Aberdeen, and London-Refined taxonomy. Both at baseline and after 12 months of intervention, dietary habits and anthropometric measures were assessed, a fasting blood sample were taken for biochemistry analysis.

Results

The participation rate at 12 months was 93.3% (n = 153 patients), 76 children in the individual-intervention and 77 children in the collective intervention. At univariate analysis, mean longitudinal change in Atherogenic Index of Plasma was greater in the individual than collective intervention (− 0.12vs. − 0.05), as well as change in triglyceride-glucose index (− 0.22vs.− 0.08) and Body Mass Index z-score (− 0.59vs.− 0.37). At multiple analysis, only change in Body Mass Index z-score remained independently associated with intervention (odds ratio 3.37).

Conclusion

In children with obesity, an individual-based nutritional and lifestyle intervention, including techniques from the CALO-RE taxonomy, could have an additional beneficial effect over a collective-based intervention, although the actual size of the effect remains to be clarified.

Trial RegistrationClinical Trials NCT03728621
Ultrasound-guided hydrostatic reduction versus fluoroscopy-guided air reduction for pediatric intussusception: a multi-center, prospective, cohort study
Authors: Liu Shu Ting , Tang Xiao Bing , Li Huan , Chen Dong , Lei Jun , Bai Yu Zuo
Published: January 2021

Background

Intussusception is the most common abdominal emergency in children. The first line treatment of uncomplicated pediatric intussusception is enema reduction. Until now, there have been no multi-center studies comparing the effectiveness and safety of UGHR and FGAR in the treatment of pediatric intussusception. The aim of this study was to compare the effectiveness and safety of the two most commonly used enema methods of pediatric intussusception: ultrasound-guided hydrostatic reduction (UGHR) and fluoroscopy-guided air reduction (FGAR).

Methods

From November 1, 2017 to October 31, 2018, we conducted a multi-center, prospective, cohort study. Children diagnosed with intussusception in four large Children’s Medical Centers in China were divided into UGHR and FGAR groups. Stratified analysis and subgroup analysis were used for further comparison. The success and recurrence rates were used to evaluate the effectiveness of enema reduction. The perforation rate was used to evaluate the safety of enema reduction.

Results

A total of 2124 cases met the inclusion criteria (UGHR group: 1119 cases; FGAR group: 1005 cases). The success and recurrence rates in the UGHR group were higher than in the FGAR group (95.80%, 9.28% vs. 93.13%, 10.65%) (P < 0.05, P > 0.05), respectively. The perforation rate in the UGHR group was 0.36% compared with 0.30% in the FGAR group (P > 0.05). Subgroup analysis showed the success rates in the UGHR group were higher than in the FGAR group of patients with onset time between 12 and 24 h (95.56% vs. 90.57%) (P < 0.05). Of patients aged 4 to 24 months, the success rates in the UGHR group were also higher than in the FGAR group (95.77% vs. 91.60%) (P < 0.05). Stratified analysis showed the success rates in the UGHR group were higher than in the FGAR group in patients with the symptom of bloody stool (91.91% vs 85.38%) (P < 0.05).

Conclusions

UGHR and FGAR are safe, nonsurgical treatment methods for acute pediatric intussusception. UGHR is superior to FGAR, no radiation risk, its success rate is higher, without a difference in perforation rate, especially for patients aged 4–24 months.

Level of evidence

Level II.
Nerve growth factor-chondroitin sulfate/hydroxyapatite-coating composite implant induces early osseointegration and nerve regeneration of peri-implant tissues in Beagle dogs
Authors: Ye Jun , Huang Bo , Gong Ping
Published: January 2021

Background

Osseointegration is the premise of the chewing function of dental implant. Nerve growth factor (NGF), as a neurotrophic factor, can induce bone healing. However, the influence of NGF-chondroitin sulfate (CS)/hydroxyapatite (HA)-coating composite implant on the osseointegration and innervations is still not entirely clear.

Materials and methods

NGF-CS/HA-coating composite implants were prepared using the modified biomimetic method. The characteristics of NGF-CS/HA-coating implants were determined using a scanning electron microscope. After NGF-CS/HA-coating implants were placed in the mandible of Beagle dogs, the early osseointegration and innervation in peri-implant tissues were assessed through X-ray, Micro-CT, maximal pull-out force, double fluorescence staining, toluidine blue staining, DiI neural tracer, immunohistochemistry, and RT-qPCR assays.

Results

NGF-CS/HA-coating composite implants were made successfully, which presented porous mesh structures with the main components (Ti and HA). Besides, we revealed that implantation of NGF-CS/HA-coating implants significantly changed the morphology of bone tissues and elevated maximum output, MAR, BIC, and nerve fiber in the mandible of Beagle dogs. Moreover, we proved that the implantation of NGF-CS/HA-coating implants also markedly upregulated the levels of NGF, osteogenesis differentiation, and neurogenic differentiation-related genes in the mandible of Beagle dogs.

Conclusion

Implantation of NGF-CS/HA-coating composite implants has significant induction effects on the early osseointegration and nerve regeneration of peri-implant tissues in the mandible of Beagle dogs.
Correlation of retinal and choroidal microvascular impairment in systemic sclerosis
Authors: Rommel Felix , Prangel David , Prasuhn Michelle , Grisanti Salvatore , Ranjbar Mahdy
Published: January 2021

Purpose

To investigate the correlation between retinal and choroidal microperfusion in patients with systemic sclerosis (SSc) using optical coherence tomography angiography (OCTA).

Methods

In this cross-sectional study SSc patients without clinical evidence of ocular involvement and healthy, age- and sex-matched volunteers were recruited. Participants underwent specific rheumatological and ophthalmological examinations, including optical coherence tomography (OCT) and OCTA. Retinal and choroidal thicknesses as well as perfusion of the retina and the choroidal sublayers were evaluated.

Results

A total of 15 SSc patients (30 eyes) with a median disease duration of 60 months and 15 matched, healthy controls (30 eyes) were recruited. OCT data revealed a significantly lower macular volume, as well as Sattler’s layer and Haller’s layer thickness in SSc patients compared to controls. In OCTA analysis, the perfusion of both retinal plexus as well as Sattler’s and Haller’s layer were significantly reduced in the SSc group. Patients with a disease duration of more than 60 months showed a statistically significant positive correlation between retinal and choroidal malperfusion, while those with a shorter disease duration did not.

Conclusion

OCTA analysis confirmed impairment of retinal and choroidal microperfusion in SSc patients, supporting the hypothesis of wide spreading vascular injury. In early stages, either the retinal or the choroidal perfusion seems to be involved, while later on, vascular impairment affects both tissues alike. Both, retinal and choroidal examinations should be considered as soon as the diagnosis of SSc is made, to avoid missing out on early alterations.
Targetable alterations in invasive pleomorphic lobular carcinoma of the breast
Authors: Riedlinger Gregory M. , Joshi Sonali , Hirshfield Kim M. , Barnard Nicola , Ganesan Shridar
Published: January 2021

Background

Invasive pleomorphic lobular carcinoma (PLC) of the breast is a subtype of invasive lobular cancer which compromises approximately 1% of all epithelial breast malignancies and is characterized by higher nuclear pleomorphism and poorer prognosis than classic invasive lobular cancer (ILC). Since PLC is more aggressive than classical ILC, we examined the underlying molecular alterations in this subtype of breast cancer to understand the possible benefit from targeted therapies.

Methods

In this study, we investigate the clinical characteristics and molecular alterations in 16 PLC from our institution. Additionally, we examined the clinical and genomic features in 31 PLC from the Cancer Genome Atlas (TCGA).

Results

Overall, our analysis of PLC found that 28% had activating ERBB2 mutations, 21% had ERBB2 amplification, and 49% activating PIK3CA mutations. Among cases from our institution, we found 19% with activating ERBB2 mutations, 25% had ERBB2 amplification, and 38% with activating PIK3CA mutations. In data from TCGA, 32% had activating ERBB2 mutations, 19% had ERBB2 amplification, and 55% had activating PIK3CA mutations. While classic ILC in TCGA had similar percentages of PIK3CA alterations compared to PLC, activating ERBB2 alterations were exceedingly rare, with no activating ERBB2 mutations and only one case with ERBB2 amplification. Interestingly, in further examining TCGA data which included FGFR1 and PTEN, 94% of PLC had alterations in ERBB2, FGFR1, or the PI3K pathway.

Conclusions

Our results show a high frequency of ERBB2 and PIK3CA alterations in PLC and suggest all PLC should be tested for potential therapeutic targeting.
Maximising recruitment to a randomised controlled trial for chronic rhinosinusitis using qualitative research methods: the MACRO conversation study
Authors: McDermott Clare , Vennik Jane , Philpott Carl , le Conte Steffi , Thomas Mike , Eyles Caroline , Little Paul , Blackshaw Helen , Schilder Anne , Hopkins Claire
Published: January 2021

Background

Randomised controlled trials (RCTs) are considered the ‘gold standard’ of medical evidence; however, recruitment can be challenging. The MACRO trial is a NIHR-funded RCT for chronic rhinosinusitis (CRS) addressing the challenge of comparing surgery, antibiotics and placebo. The embedded MACRO conversation study (MCS) used qualitative research techniques pioneered by the University of Bristol QuinteT team to explore recruitment issues during the pilot phase, to maximise recruitment in the main trial.

Methods

Setting: Five outpatient Ear Nose and Throat (ENT) departments recruiting for the pilot phase of the MACRO trial (ISRCTN Number: 36962030, prospectively registered 17 October 2018). We conducted a thematic analysis of telephone interviews with 18 recruiters and 19 patients and 61 audio-recordings of recruitment conversations. We reviewed screening and recruitment data and mapped patient pathways at participating sites. We presented preliminary findings to individual site teams. Group discussions enabled further exploration of issues, evolving strategies and potential solutions. Findings were reported back to the funder and used together with recruitment data to justify progression to the main trial.

Results

Recruitment in the MACRO pilot trial began slowly but accelerated in time to progress successfully to the main trial. Research nurse involvement was pivotal to successful recruitment. Engaging the wider network of clinical colleagues emerged as an important factor, ensuring the patient pathway through primary and secondary care did not inadvertently affect trial eligibility. The most common reason for patients declining participation was treatment preference. Good patient-clinician relationships engendered trust and supported patient decision-making. Overall, trial involvement appeared clearly presented by recruiters, possibly influenced by pre-trial training. The weakest area of understanding for patients appeared to be trial medications. A clear presentation of medical and surgical treatment options, together with checking patient understanding, had the potential to allay patient concerns.

Conclusion

The MACRO conversation study contributed to the learning process of optimising recruitment by helping to identify and address recruitment issues. Although some issues were trial-specific, others have applicability to many clinical trial situations. Using qualitative research techniques to identify/explore barriers and facilitators to recruitment may be valuable during the pilot phase of many RCTs including those with complex designs.