bluuebunny/crossref_metadata_2025 huggingface dataset:
Late coronary artery injury following chemoradiotherapy for thymic carcinoma: a case report
Authors: Hu Sigan , Wang Jun , Cui Zhen , Zhou Yongchun , Gao Dasheng
Published: May 2024

Introduction

Surgery remains the primary treatment modality for thymic carcinoma, with adjuvant radiotherapy being recommended to effectively mitigate local recurrence and metastasis rates subsequent to incomplete or complete resection. Chemoradiotherapy has the potential to induce coronary artery occlusion, thereby potentially impacting patients’ long-term survival rates. The existing literature currently lacks comprehensive research on the lesion characteristics of coronary artery injury resulting from chemoradiotherapy.

Case presentation

The male patient, aged 55, was admitted to the hospital due to recurrent chest tightness and pain persisting for one week. Notably, the patient had previously undergone curative resection surgery for thymic carcinoma seven years ago. After the surgical procedure, the patient underwent a course of adjuvant chemotherapy comprising docetaxel and platinum. 11 months later, imaging examination diagnosed tumor recurrence, and concurrent chemoradiotherapy was administered at a total dose of 62 Gy/31F for planning gross target volume (PGTV) and 54 Gy/31F for planning target volume (PTV) with 2 cycles of paclitaxel and cisplatin. Re-admission of the patient occurred after a 7-year interval subsequent to the completion of concurrent chemoradiotherapy, leading to a subsequent diagnosis of acute non-ST segment elevation myocardial infarction. Following administration of antiplatelet, anticoagulant, and anti-myocardial ischemia therapy, coronary angiography revealed the presence of a bifurcation lesion at the distal end of the left main trunk. Intravascular ultrasound (IVUS) examination demonstrated significant negative remodeling of both the main trunk and its branches at the bifurcation site, characterized by minimal atherosclerotic plaque components.

Conclusions

Chemoradiotherapy may induce damage to endothelial cells, resulting in an inflammatory response. Negative remodeling of blood vessels is likely to occur, primarily characterized by vasoconstriction but with less atherosclerotic plaque burden. Routine stent implantation in negatively remodeled areas may lead to vascular rupture, necessitating intravascular imaging examination.
Evaluation of the prevalence of Aeromonas spp., Campylobacter spp., and Clostridioides difficile in immunocompromised children with diarrhea
Authors: Heydari Hosein , Iranikhah Abolfazl , Ghasemi Ahmad , Mohammadbeigi Abolfazl , Sadat-Mirei Seyed Ali , Shams Saeed , Kermani Somayeh
Published: May 2024

Aim

Diarrhea is a common disease in immunocompromised patients and can be associated with greater morbidity and even mortality. Therefore, the present study was designed to determine the prevalence of Aeromonas spp., Campylobacter spp., and C. difficile among immunocompromised children.

Methods

This study was conducted on 130 stool samples from patients with diarrhea who had defects in the immune system and were referred to Hazrat Masoumeh Children’s Hospital in Qom. Demographic information, clinical symptoms, immune status, and duration of chemotherapy were also recorded for each child. DNAs were extracted from the stool, and then direct PCR assays were done by specific primers for the detection of Aeromonas spp., Campylobacter spp., and toxigenic C. difficile, including tcdA/B and cdtA/B genes. Co-infection in patients was also evaluated.

Results

60.8% and 39.2% were male and female, respectively, with a m ± SD age of 56.72 ± 40.49 months. Most cases of immunocompromised states were related to Acute Lymphocytic Leukemia (77.7%) and Non-Hodgkin Lymphoma (14.6%). 93.1% of patients were undergoing chemotherapy during the study. Among patients, most clinical symptoms were related to bloody diarrhea (98.5%) and fever (92.3%). Based on PCR, 14.6, 9.2, and 1.5% were positive for Aeromonas spp., C. difficile, and C. jejuni, respectively. Among the C. difficile-positive cases, the tcdA gene was only detected in one patient. In total, three co-infections were identified, which included Aeromonas spp./C. difficile (tcdA+), C. jejuni/C. difficile, and C. jejuni/Aeromonas spp.

Conclusions

This is the first study in Iran to investigate the simultaneous prevalence of some pathogens in immunocompromised children with diarrhea. Because Aeromonas spp., Campylobacter spp., and C. difficile are not routinely detected in some laboratories, infections caused by them are underappreciated in the clinic. Our results showed that these pathogens are present in our region and can cause gastroenteritis in children, especially those with underlying diseases. Therefore, increasing the level of hygiene in some areas and controlling bacterial diarrheal diseases should be given more attention by health officials.
Frailty, but not cognitive impairment, improves mortality risk prediction among those with chronic kidney disease—a nationally representative study
Authors: Hong Jingyao , Chu Nadia M. , Cockey Samuel G. , Long Jane , Cronin Nicolai , Ghildayal Nidhi , Hall Rasheeda K. , Huisingh-Scheetz Megan , Scherer Jennifer , Segev Dorry L. , McAdams-DeMarco Mara A.
Published: May 2024

Background

Though older adults with chronic kidney disease (CKD) have a greater mortality risk than those without CKD, traditional risk factors poorly predict mortality in this population. Therefore, we tested our hypothesis that two common geriatric risk factors, frailty and cognitive impairment, and their co-occurrence, might improve mortality risk prediction in CKD.

Methods

Among participants aged ≥ 60 years from National Health and Nutrition Examination Survey (2011–2014), we quantified associations between frailty (physical frailty phenotype) and global/domain-specific cognitive function (immediate-recall [CERAD-WL], delayed-recall [CERAD-DL], verbal fluency [AF], executive function/processing speed [DSST], and global [standardized-average of 4 domain-specific tests]) using linear regression, and tested whether associations differed by CKD using a Wald test. We then tested whether frailty, global cognitive impairment (1.5SD below the mean), or their combination improved prediction of mortality (Cox models, c-statistics) compared to base models (likelihood-ratios) among those with and without CKD.

Results

Among 3,211 participants, 1.4% were cognitively impaired, and 10.0% were frail; frailty and cognitive impairment co-occurrence was greater among those with CKD versus those without (1.2%vs.0.1%). Frailty was associated with worse global cognitive function (Cohen’s d = -0.26SD,95%CI -0.36,-0.17), and worse cognitive function across all domains; these associations did not differ by CKD (pinteractions > 0.05). Mortality risk prediction improved only among those with CKD when accounting for frailty (p[likelihood ratio test] < 0.001) but not cognitive impairment.

Conclusions

Frailty is associated with worse cognitive function regardless of CKD status. While CKD and frailty improved mortality prediction, cognitive impairment did not. Risk prediction tools should incorporate frailty to improve mortality prediction among those with CKD.
Factors conditioning pain control and reduction in post-cesarean section parturients: a cross-sectional study
Authors: Pilewska-Kozak Anna Bogusława , Dziurka Magdalena , Bałanda –Bałdyga Agnieszka , Monist Marta Joanna , Kopiel Ewelina , Jurek Krzysztof , Łęcka Anna Francesca , Dobrowolska Beata
Published: May 2024

Background

Pain experienced by women in the perinatal period constitutes a complex and multifaceted phenomenon. The aim of the study was to assess conditions of pain locus of control and pain reduction in post-cesarean section parturients.

Materials and methods

A cross-sectional quantitative study with convenience sampling was performed among 175 hospitalized post-cesarean section women in hospitals in Eastern Poland in accordance with the Strengthening the Reporting of Observational studies in Epidemiology (STROBE) statement. A self-design questionnaire regarding general information and obstetrics/gynaecology medical interview, The Pain Coping Strategies Questionnaire (CSQ) and The Beliefs about Pain Control Questionnaire (BPCQ) were used. The inclusion criteria were as follows (1) age of ⩾18 years old; (2) cesarean section (CS); (3) period from the 13th hour to the end of the 72nd hour after the procedure; and (4) informed consent. The data was analyzed with IBM SPSS Statistics.

Results

Internal locus of control (M = 14.02) was provided the highest value by the parturients and followed by chance events (M = 12.61) and doctors’ power (M = 12.18). Dominant coping with pain strategies in the post-cesarean parturients were coping self-statements (M = 19.06), praying or hoping (M = 18.86). The parturients assessed their pain coping (M = 3.31) strategies along with pain reduction (M = 3.35) at the moderate level. Higher pain control was correlated with cognitive pain coping strategies (β = 0.305; t = 4.632; p < 0.001), internal pain control β = 0.191; t = 2.894; p = 0.004), cesarean section planning (β = -0.240; t = -3.496; p = 0.001) and past medical history of CS (β = 0.240; t = 3.481; p = 0.001). The skill of reduction of pain was positively associated with cognitive pain coping strategies (β = 0.266; t = 3.665; p < 0.001) and being in subsequent pregnancy (β = 0.147; t = 2.022; p = 0.045). Catastrophizing and hoping were related to lower competences of coping with pain (B = − 0.033, SE = 0.012, β = − 0.206, T = -2.861).

Conclusions

The study allowed for identification and better comprehension of factors conditioning pain control and pain reduction in parturients after the cesarean section. Furthermore, a stronger belief that pain can be dealt with is found in the parturients characterized by cognitive pain coping strategies and internal pain locus of control. The skill of reduction of pain is related to cognitive coping strategy and procreation status.
Cost-effectiveness of ivosidenib versus chemotherapy for previously treated IDH1-mutant advanced intrahepatic cholangiocarcinoma in Taiwan
Authors: Chen Kuei-An , Huang Wei-Ming , Chen Eric Yi-Ting , Ho Pei-Kuan , Chueh Chen-Han , Wen Yu-Wen , Chen Ming-Huang , Chiang Nai-Jung , Tsai Yi-Wen
Published: May 2024

Background

International guidelines recommend ivosidenib followed by modified FOLFOX (mFOLFOX) for advanced intrahepatic cholangiocarcinoma (ICC) with isocitrate dehydrogenase 1 (IDH1) mutations. Taiwan National Health Insurance covers only fluorouracil/leucovorin (5-FU/LV) chemotherapy for this ICC group, and there has been no prior economic evaluation of ivosidenib. Therefore, we aimed to assess ivosidenib’s cost-effectiveness in previously treated, advanced ICC-presenting IDH1 mutations compared with mFOLFOX or 5-FU/LV.

Methods

A 3-state partitioned survival model was employed to assess ivosidenib’s cost-effectiveness over a 10-year horizon with a 3% discount rate, setting the willingness-to-pay threshold at 3 times the 2022 GDP per capita. Efficacy data for Ivosidenib, mFOLFOX, and 5-FU/LV were sourced from the ClarIDHy, ABC06, and NIFTY trials, respectively. Ivosidenib’s cost was assumed to be NT$10,402/500 mg. Primary outcomes included incremental cost-effectiveness ratios (ICERs) and net monetary benefit. Deterministic sensitivity analyses (DSA) and probabilistic sensitivity analyses (PSA) were employed to evaluate uncertainty and explore price reduction scenarios.

Results

Ivosidenib exhibited ICERs of NT$6,268,528 and NT$5,670,555 compared with mFOLFOX and 5-FU/LV, respectively, both exceeding the established threshold. PSA revealed that ivosidenib was unlikely to be cost-effective, except when it was reduced to NT$4,161 and NT$5,201/500 mg when compared with mFOLFOX and 5-FU/LV, respectively. DSA underscored the significant influence of ivosidenib’s cost and utility values on estimate uncertainty.

Conclusions

At NT$10,402/500 mg, ivosidenib was not cost-effective for IDH1-mutant ICC patients compared with mFOLFOX or 5-FU/LV, indicating that a 50–60% price reduction is necessary for ivosidenib to be cost-effective in this patient group.
Construction and validation of a novel tumor morphology immune inflammatory nutritional score (TIIN score) for intrahepatic cholangiocarcinoma: a multicenter study
Authors: Zhang Haofeng , Huang Guan , Li Qingshan , Wang Yanbo , Yang Zhenwei , Chen Pengyu , Yuan Hao , Chen Kunlun , Meng Bo , Yu Haibo
Published: May 2024

Background

Tumor morphology, immune function, inflammatory levels, and nutritional status play critical roles in the progression of intrahepatic cholangiocarcinoma (ICC). This multicenter study aimed to investigate the association between markers related to tumor morphology, immune function, inflammatory levels, and nutritional status with the prognosis of ICC patients. Additionally, a novel tumor morphology immune inflammatory nutritional score (TIIN score), integrating these factors was constructed.

Methods

A retrospective analysis was performed on 418 patients who underwent radical surgical resection and had postoperative pathological confirmation of ICC between January 2016 and January 2020 at three medical centers. The cohort was divided into a training set (n = 272) and a validation set (n = 146). The prognostic significance of 16 relevant markers was assessed, and the TIIN score was derived using LASSO regression. Subsequently, the TIIN-nomogram models for OS and RFS were developed based on the TIIN score and the results of multivariate analysis. The predictive performance of the TIIN-nomogram models was evaluated using ROC survival curves, calibration curves, and clinical decision curve analysis (DCA).

Results

The TIIN score, derived from albumin-to-alkaline phosphatase ratio (AAPR), albumin–globulin ratio (AGR), monocyte-to-lymphocyte ratio (MLR), and tumor burden score (TBS), effectively categorized patients into high-risk and low-risk groups using the optimal cutoff value. Compared to individual metrics, the TIIN score demonstrated superior predictive value for both OS and RFS. Furthermore, the TIIN score exhibited strong associations with clinical indicators including obstructive jaundice, CEA, CA19-9, Child–pugh grade, perineural invasion, and 8th edition AJCC N stage. Univariate and multivariate analysis confirmed the TIIN score as an independent risk factor for postoperative OS and RFS in ICC patients (p < 0.05). Notably, the TIIN-nomogram models for OS and RFS, constructed based on the multivariate analysis and incorporating the TIIN score, demonstrated excellent predictive ability for postoperative survival in ICC patients.

Conclusion

The development and validation of the TIIN score, a comprehensive composite index incorporating tumor morphology, immune function, inflammatory level, and nutritional status, significantly contribute to the prognostic assessment of ICC patients. Furthermore, the successful application of the TIIN-nomogram prediction model underscores its potential as a valuable tool in guiding individualized treatment strategies for ICC patients. These findings emphasize the importance of personalized approaches in improving the clinical management and outcomes of ICC.
A case report of classic galactosemia with a GALT gene variant and a literature review
Authors: Wang Yong-cai , Lan Lian-cheng , Yang Xia , Xiao Juan , Liu Hai-xin , Shan Qing-wen
Published: May 2024

Background

Galactosemia is an autosomal recessive disorder resulting from an enzyme defect in the galactose metabolic pathway. The most severe manifestation of classic galactosemia is caused by galactose-1-phosphate uridylyltransferase (GALT) deficiency, and this condition can be fatal during infancy if left untreated. It also may result in long-term complications in affected individuals.

Case presentation

This report describes a patient whose initial clinical symptoms were jaundice and liver dysfunction. The patient’s liver and coagulation functions did not improve after multiple admissions and treatment with antibiotics, hepatoprotective and choleretic agents and blood transfusion. Genetic analysis revealed the presence of two variants in the GALT gene in the compound heterozygous state: c.377 + 2dup and c.368G > C (p.Arg123Pro). Currently, the variant locus (c.377 + 2dup) in the GALT gene has not been reported in the Human Gene Mutation Database (HGMD), while c.368G > C (p.Arg123Pro) has not been reported in the Genome Aggregation Database (GnomAD) nor the HGMD in East Asian population. We postulated that the two variants may contribute to the development of classical galactosemia.

Conclusions

Applications of whole-exome sequencing to detect the two variants can improve the detection and early diagnosis of classical galactosemia and, more specifically, may identify individuals who are compound heterozygous with variants in the GALT gene. Variants in the GALT gene have a potential therapeutic significance for classical galactosemia.
Trust in primary health care and COVID-19 vaccine uptake among Iranian pediatric: a web-based cross-sectional survey
Authors: Sarbazi Ehsan , Masoudi Nazanin , Mehri Ahmad , Esfanjani Robab Mehdizadeh , Azizi Hosein , Soleimanpour Maryam , Pouraghaei Mahboub , Soleimanpour Hassan
Published: May 2024

Background

Children are the most vulnerable group to diseases. Thus, it’s critical to evaluate parents’ or guardians’ willingness to vaccinate their children. This study aims to investigate the prevalence and predictors of pediatric COVID-19 vaccination in Iran and its relationship with trust in the Primary Health Care (PHC) system.

Method

A cross-sectional online survey of 549 Iranian parents was conducted between January and March 2023. This study collected data from all provinces of Iran using a questionnaire shared on Google Forms and various social media platforms. After considering various background factors, we used a multivariable logistic regression model. This model explored how trust in the PHC system and parent-related and child-related factors were related to parents’ vaccine uptake for their children.

Results

Of 549 parents aged between 19 and 67 years (median = 38 years), 65.2% (358) were female. The prevalence of vaccine uptake among parents was 46.8%. After adjusting for background features, child’s age (adjusted odds ratio [AOR] 0.81, 95% CI 0.71–0.91), vaccine doses (1-dose: AOR 14.72, 95% CI 6.44–33.65, 2-dose: AOR 32.54, 95% CI 15.22–69.57), child’s disease (AOR 5.31, 95% CI 2.19–12.85), and trust in PHC (AOR 1.01, 95% CI 1.00–1.02) were associated with parental uptake of the COVID-19 vaccine.

Conclusions

The findings of this study suggest that the child’s age, vaccine doses received, diseases, and trust in PHC are significant predictors of parental uptake of the COVID-19 vaccine for children in Iran. The results can be used in service planning regarding children’s COVID-19 vaccination.
Factors influencing risk perception during Public Health Emergencies of International Concern (PHEIC): a scoping review
Authors: Yin Jason Dean-Chen , Lui Juliana Nga-Man
Published: May 2024

The unknownness and dread potential of a risk event shapes its perceived risk. A public health emergency of international concern (PHEIC) declaration by the World Health Organisation (WHO) is a signal for such an event. Understanding perceived risk then shapes risk-avoiding behaviours, important for health prevention. The review aims to consolidate the determinants of risk perception during a PHEIC, underscoring the need for grounding in context and theory. Studies published from 2010 until end-2020, searching PubMed, PsycINFO, MedlinePlus, PubPsych, and CINAHL, were included. Studies with only biological conceptualisations of risk, or no association to risk perception, were excluded. A total of 65 studies were included. Quality of the cross-sectional studies was assessed using Newcastle Ottawa Scale (NOS), yielding an average of 5.4 stars (out of 10). Factors were classified into three broad categories – individual, contextual, and media. Individual risk factors include emotions; beliefs, trust, and perceptions; immutable physical traits (sex, age, ethnicity); mutable traits (education, income, etc.); and knowledge, with no definitive correlation to risk perception. Contextual traits include pandemic experience, time, and location, with only time negatively correlated to risk perception. Media traits include exposure, attention, and framing of media, with no clear association to risk perception. One limitation is excluding a portion of COVID-19 studies due to censoring. Still, this lack of consensus highlights the need to better conceptualise “risk perception”. Specifying the context and timing is also important since jurisdictions experience different outbreaks depending on outbreak histories. Using theories to ground risk perception research assists with these tasks.
Process evaluation of implementation of the early stages of a whole systems approach to obesity in a small Island
Authors: MacKinlay Brittney , Heneghan Kate , Potts Alexandra J. , Radley Duncan , Sanders George , Walker Ian F.
Published: May 2024

Background

The small Atlantic island of St Helena is a United Kingdom Overseas Territory (UKOT) with a high prevalence of childhood obesity (over a quarter of 4–5 and 10–11 year olds) and, anecdotally, adulthood obesity and its associated health detriments. St Helena have taken a whole systems approach to obesity (WSAO) to address the issue. A WSAO recognises the factors that impact obesity as a complex system and requires a ‘health in all policies’ approach. UK academic and public health technical support was provided to the local St Helena delivery team. This process evaluation sought to explore the early stages of the WSAO implementation and implications for the transferability of the approach to other small island developing states and UKOT.

Methods

Data was collected via eight semi-structured interviews, paper based and online surveys, and document analysis. Thematic analysis was used to analyse the data.

Results

The analysis identified three factors which aided the first phase of WSAO implementation: (1) senior leaders support for the approach; (2) the academic support provided to establish and develop the approach; and (3) effective adaptation of UK Government resources to suit the local context. Key challenges of early implementation included: maintaining and broadening stakeholder engagement; limited local workforce capacity and baseline knowledge related to obesity and systems thinking; and limited capacity for support from the UK-based academic team due to contract terms and COVID-19 restrictions.

Conclusions

Early stages of implementation of a WSAO in a UKOT can be successful when using UK’s resources as a guide and adapting them to a small island context. All participants recommended other small islands adopt this approach. Continued senior support, dedicated leadership, and comprehensive community engagement is needed to progress implementation and provide the foundation for long-term impact. Small island developing states considering adopting a WSAO should consider political will, senior level buy-in and support, funding, and local workforce knowledge and capacity to enable the best chances of successful and sustainable implementation.
Estimating thoracic kyphosis without information on upper thoracic kyphosis: an observational study on 455 patients examined by EOS imaging
Authors: Ghandhari Hasan , Javanbakht Mohammad , Nikouei Farshad , Shakeri Mohammadreza , Cegolon Luca , Motalebi Mohsen
Published: May 2024

Background

Physiological thoracic kyphosis (TK) allows sagittal balance of human body. Unlike lumbar lordosis (LL), TK has been relatively neglected in the literature. EOS is an imaging technique employing high-sensitivity xenon particles, featured by low-dose exposure combined with high accuracy compared to conventional radiography. The aim of this study was to investigate predictors of TK in patients with phyiological spine morphology using EOS imaging.

Methods

EOS images of 455 patients without spinal anomalies were retrospectively assessed for TK (T1- T12), upper thoracic kyphosis (UTK, T1-T5), lower thoracic kyphosis (LTK, T5-T12), LL (L1-S1) and pelvic incidence (PI). The latter curves were measured by two researchers separately and the average of the two measurements was used for further analysis.

Spearman non-parametric correlation was estimated for age, PI, LL, LTK, UTK and TK. Multiple robust linear regression analysis was employed to estimate TK, controlling for the effect of age, sex, LL and LTK.

Results

The mean age of patients was 28.3 ± 19.2 years and 302 (66.4%) of them were females. The mean TK, UTK and LTK was 45.5° ± 9.3, 16 ± 7.4° and 29.7° ± 8.9, respectively. The mean UTK in people under 40 years of age was 17.0° ± 7.2, whereas for patients 40+ years old it was 13.6° ± 7.4. At univariable analysis TK positively correlated with UTK (p<0.001), LTK (p<0.001) an LL (p<0.001). At multivariable linear regression TK increased with LTK (RC = 0.67; 95%CI: 0.59; 0.75) or LL (RC = 0.12; 95%CI: 0.06; 0.18), whereas it decreased with age (RC = -0.06; 95%CI: -0.09;—0.02).

Conclusion

If EOS technology is available, the above linear regression model could be used to estimate TK based upon information on age, sex, LL and LTK. Alternatively, TK could be estimated by adding to LTK 17.0° ± 7.4 for patients < 40 years of age, or 13.6° ± 7.4 in patients 40 + years old. The evidence from the present study may be used as reference for research purposes and clinical practice, including spine examination of particular occupational categories or athletes.
Impact of self-assessment on dental student’s performance in pre-clinical conservative dentistry course
Authors: Mittal Priya , Jadhav Ganesh R. , Pawar Mansing , Banerjee Sitikantha , Wangaskar Sneha , Di Blasio Marco , Cervino Gabriele , Minervini Giuseppe
Published: May 2024

Background

Self-assessment (SA) is an interactive course that endorses the accomplishment of learning objectives through learners’ identification of insufficiencies in their didactic knowledge and pre-clinical skills. This study was planned to determine whether there is any improvement in the faculty assessment (FA) score following the implementation of SA in the Pre-clinical Conservative Dentistry Course.

Methods

Fifty-four first-semester dental students were given an introductory lecture followed by a demonstration for Class I Cavity Preparation in typhodont mandibular first molar. At the end of the demonstration, the Scoring Rubric (SR) was explained point-wise in the prepared cavities. During the next session, all students performed Class I cavity preparation and they were given an assessment sheet to enter their scores (SA1). All teeth were evaluated by the Grading Faculties in a blinded manner (FA1). Each participant was explained the difference in their respective SA1 from FA1 and their queries were resolved individually. During the next sessions, Students and Grading Faculties followed the same protocol and scores were recorded as SA2, FA2, SA3 and FA3.

Results

The mean score of SA1 was significantly higher than that of FA1 (p < 0.001). However, no significant difference was obtained between SA and FA in the second (p = 0.352) and third (p = 0.434) assessments. In contrast with first assessment, mean marks obtained in FA were higher compared to SA in both second and third assessments. There was a statistically significant improvement in mean marks obtained by the students over time (p < 0.001).

Conclusion

SA endorsed student-faculty communication and enhanced student’s poise and technical skills in operative pre-clinical dentistry.
Application of personalized templates in minimally invasive management of coronal dens invaginatus: a report of two cases
Authors: Li Mingming , Wang Guosong , Zhu Fangzhi , Jiang Han , Yang Yingming , Cheng Ran , Hu Tao , Zhang Ru
Published: May 2024

Background

Treating the coronal dens invaginatus (CDI) with pulp infection commonly involves the removal of invagination, which increases the risk of perforation and fracture, and compromises the tooth structure. Minimally invasive endodontic management of CDI is highly recommended. This report describes two cases of type II CDI with the application of personalized templates.

Case presentation

Two cases of type II CDI, affecting the main root canal in a maxillary canine and a lateral incisor, were diagnosed. A guided endodontics (GE) approach was applied. Cone-beam computed tomography and intraoral scans were imported and aligned in a virtual planning software to design debridement routes and templates. The MICRO principle (which involves the aspects of Mechanical (M) debridement, Irrigation (I), Access cavities (C), Rectilinear routes (R), and Obstruction (O)) was proposed for designing optimal debridement routes for future applications. The templates were innovatively personalized and designed to preserve the tooth structure maximally while effectively debriding the root canal. Root canal treatment with supplementary disinfection was then performed. The follow-up of the two patients revealed favorable clinical and radiographic outcomes.

Conclusions

The GE approach could be a feasible method for preserving healthy dental structure while effectively debriding the root canal, thereby achieving successful and minimally invasive endodontic treatment for CDI.
A scoping review of ethics review processes during public health emergencies in Africa
Authors: Orievulu Kingsley , Hinga Alex , Nkosi Busisiwe , Ngwenya Nothando , Seeley Janet , Akanlu Anthony , Tindana Paulina , Molyneux Sassy , Kinyanjui Samson , Kamuya Dorcas
Published: May 2024

Background

The COVID-19 pandemic forced governments, multilateral public health organisations and research institutions to undertake research quickly to inform their responses to the pandemic. Most COVID-19-related studies required swift approval, creating ethical and practical challenges for regulatory authorities and researchers. In this paper, we examine the landscape of ethics review processes in Africa during public health emergencies (PHEs).

Methods

We searched four electronic databases (Web of Science, PUBMED, MEDLINE Complete, and CINAHL) to identify articles describing ethics review processes during public health emergencies and/or pandemics. We selected and reviewed those articles that were focused on Africa. We charted the data from the retrieved articles including the authors and year of publication, title, country and disease(s) reference, broad areas of (ethical) consideration, paper type, and approach.

Results

Of an initial 4536 records retrieved, we screened the titles and abstracts of 1491 articles, and identified 72 articles for full review. Nine articles were selected for inclusion. Of these nine articles, five referenced West African countries including Liberia, Guinea and Sierra Leone, and experiences linked to the Ebola virus disease. Two articles focused on South Africa and Kenya, while the other two articles discussed more general experiences and pitfalls of ethics review during PHEs in Africa more broadly. We found no articles published on ethics review processes in Africa before the 2014 Ebola outbreak, and only a few before the COVID-19 outbreak. Although guidelines on protocol review and approval processes for PHEs were more frequently discussed after the 2014 Ebola outbreak, these did not focus on Africa specifically.

Conclusions

There is a gap in the literature about ethics review processes and preparedness within Africa during PHEs. This paper underscores the importance of these processes to inform practices that facilitate timely, context-relevant research that adequately recognises and reinforces human dignity within the quest to advance scientific knowledge about diseases. This is important to improve fast responses to PHEs, reduce mortality and morbidity, and enhance the quality of care before, during, and after pandemics.
Co-creating a continuous leadership development program in rural municipal healthcare – an action research study
Authors: Hartviksen Trude Anita , Solbakken Rita , Strauman Lars , Magnussen Inger-Lise
Published: May 2024

Background

An increasingly complex healthcare system entails an urgent need for competent and resilient leadership. However, there is a lack of extensive research on leadership development within healthcare. The knowledge gaps extend to various frameworks and contexts, particularly concerning municipal healthcare, knowledge leadership, and the application of knowledge in the field of practice. This study is the first in a larger action research project that aims to co-create a knowledge-based continuous leadership development program for healthcare in a rural Arctic municipality. This present study aims to explore the knowledge and experiences of the participating healthcare leaders to develop a common basis for co-creating the program.

Methods

This hermeneutical study presents the first cycle of the larger action research project. An appreciative approach facilitated the project. Twenty-three healthcare leaders from three different leadership levels attended and evaluated two leadership development workshops and participated in four focus groups. The data were analyzed using Braun and Clarke’s reflexive thematic analysis.

Results

Two main themes were identified: (1) changing from striving solo players to team players, and (2) learning to handle a conflicting and complex context. These results influenced how the leadership development program based on the participants’ co-creation was organized as a collective and relational process rather than an individual competence replenishment.

Conclusions

The knowledge and experiences of healthcare leaders led to the co-creation of a knowledge-based continuous leadership development program based on the facilitated interaction of four essential elements: (1) competence development, (2) structures for interaction, (3) interpersonal safety, and (4) collective values and goals. The interaction was generated through trusted reflection facilitated by appreciative inquiry. The four elements and core played a crucial role in fostering relationships and facilitating learning, driving transformative change in this leadership development program. The study’s results provide a solid foundation for further co-creating the program. However, more research is needed to fully explore the practical application and overall significance.
Advocacy, experience sharing and action planning toward raising additional financing for primary health care: spending more and spending better towards universal health coverage
Authors: Kizza Diana , Nabyonga-Orem Juliet , Kwesiga Brendan , Muniz Maria , Chukwujekwu Ogochukwu , Ngwakum Paul
Published: May 2024

Background

Reallocation of funding to respond the covid-19 pandemic, against a backdrop of longstanding underfunded health systems and high out of pocket expenditures for health, affected access to health services for households, especially those without social protection. These highlighted the urgency in curbing the impact of disruptions on progress towards Universal Health Coverage (UHC) goals. Strategic investments in Primary Health Care (PHC) can help spur the necessary momentum.

Methods

Under the collaborative platform of the Harmonization for Health in Africa’s Health Financing Technical Working Group; UNICEF Regional Office for East and Southern Africa and WHO Regional Office for Africa convened the first PHC financing forum for 21 countries across the Eastern and Southern Africa Region. The three-day forum engaged key health and financing decision makers in constructive dialogue to identify practical actions and policy changes needed to accelerate delivery of UHC through improvements in PHC financing mechanisms and arrangements. The forum was attended by over 130 senior policy makers and technicians from governments, United Nations agencies and nonstate actors drawn from within country, regional and affiliating headquarter institutions.

Results

The Regional Forum engaged participants in meaningful, and constructive discussions. Five themes emerged (1) regular measurement and monitoring of PHC services and spending (2) increasing investments in PHC (3) enhancing efficiency, effectiveness, and equity of PHC spending, (4) ensuring an enabling environment to invest more and better in PHC, and (5) better partnerships for the realization of commitments. An outcome statement summarizing the main recommendations of the meeting was approved at the end of the forum, and action plans were developed by 14 government delegations to improve PHC financing within country-specific context and priorities.

Conclusions and recommendations

The aims of this meeting in augmenting the political will created through the Africa Leadership Meeting (ALM), by catalyzing technical direction for increased momentum for improved health financing across all African countries was achieved. Peer exchanges offered practical approaches countries can take to improve health financing in ways that are suited to regional context providing a channel for incremental improvements to health outcomes in the countries.
Frontline perspectives on barriers to care for patients with California Medicaid: a qualitative study
Authors: Faiz Jessica , Blegen Mariah , Nuñez Vanessa , Gonzalez Daniel , Stokes Daniel C. , Truong Kevin , Ryan Gery , Briggs-Malonson Medell , Kahn Katherine L.
Published: May 2024

Background

While insurance is integral for accessing healthcare in the US, coverage alone may not ensure access, especially for those publicly insured. Access barriers for Medicaid-insured patients are rooted in social drivers of health, insurance complexities in the setting of managed care plans, and federal- and state-level policies. Elucidating barriers at the health system level may reveal opportunities for sustainable solutions.

Methods

To understand barriers to ambulatory care access for patients with Medi-Cal (California’s Medicaid program) and identify improvement opportunities, we performed a qualitative study using semi-structured interviews of a referred sample of clinicians and administrative staff members experienced with clinical patient encounters and/or completion of referral processes for patients with Medi-Cal (n = 19) at a large academic medical center. The interview guide covered the four process steps to accessing care within the health system: (1) scheduling, (2) referral and authorization, (3) contracting, and (4) the clinical encounter. We transcribed and inductively coded the interviews, then organized themes across the four steps to identify perceptions of barriers to access and improvement opportunities for ambulatory care for patients with Medi-Cal.

Results

Clinicians and administrative staff members at a large academic medical center revealed barriers to ambulatory care access for Medi-Cal insured patients, including lack of awareness of system-level policy, complexities surrounding insurance contracting, limited resources for social support, and poor dissemination of information to patients. Particularly, interviews revealed how managed Medi-Cal impacts academic health systems through additional time and effort by frontline staff to facilitate patient access compared to fee-for-service Medi-Cal. Interviewees reported that this resulted in patient care delays, suboptimal care coordination, and care fragmentation.

Conclusions

Our findings highlight gaps in system-level policy, inconsistencies in pursuing insurance authorizations, limited resources for scheduling and social work support, and poor dissemination of information to and between providers and patients, which limit access to care at an academic medical center for Medi-Cal insured patients. Many interviewees additionally shared the moral injury that they experienced as they witnessed patient care delays in the absence of system-level structures to address these barriers. Reform at the state, insurance organization, and institutional levels is necessary to form solutions within Medi-Cal innovation efforts.
PARP1-DOT1L transcription axis drives acquired resistance to PARP inhibitor in ovarian cancer
Authors: Liu Chaohua , Li Jiana , Xu Fei , Chen Lihua , Ni Mengdong , Wu Jiangchun , Zhao Haiyun , Wu Yangjun , Li Jiajia , Wu Xiaohua , Chen Xiaojun
Published: May 2024

Background

Poly (ADP-ribose) polymerase inhibitor (PARPi) resistance poses a significant challenge in ovarian carcinoma (OC). While the role of DOT1L in cancer and chemoresistance is acknowledged, its specific role in PARPi resistance remains unclear. This study aims to elucidate the molecular mechanism of DOT1L in PARPi resistance in OC patients.

Methods

This study analyzed the expression of DOT1L in PARPi-resistant cell lines compared to sensitive ones and correlated it with clinical outcomes in OC patients. Comprehensive in vitro and in vivo functional experiments were conducted using cellular and mouse models. Molecular investigations, including RNA sequencing, chromatin immunoprecipitation (ChIP) and Cleavage Under Targets and Tagmentation (CUT&Tag) assays, were employed to unravel the molecular mechanisms of DOT1L-mediated PARPi resistance.

Results

Our investigation revealed a robust correlation between DOT1L expression and clinical PARPi resistance in non-BRCA mutated OC cells. Upregulated DOT1L expression in PARPi-resistant tissues was associated with diminished survival in OC patients. Mechanistically, we identified that PARP1 directly binds to the DOT1L gene promoter, promoting transcription independently of its enzyme activity. PARP1 trapping induced by PARPi treatment amplified this binding, enhancing DOT1L transcription and contributing to drug resistance. Sequencing analysis revealed that DOT1L plays a crucial role in the transcriptional regulation of PLCG2 and ABCB1 via H3K79me2. This established the PARP1-DOT1L-PLCG2/ABCB1 axis as a key contributor to PARPi resistance. Furthermore, we discovered that combining a DOT1L inhibitor with PARPi demonstrated a synergistic effect in both cell line-derived xenograft mouse models (CDXs) and patient-derived organoids (PDOs).

Conclusions

Our results demonstrate that DOT1L is an independent prognostic marker for OC patients. The PARP1-DOT1L/H3K79me2-PLCG2/ABCB1 axis is identified as a pivotal contributor to PARPi resistance. Targeted inhibition of DOT1L emerges as a promising therapeutic strategy for enhancing PARPi treatment outcomes in OC patients.
The profile of steroid hormones in human fetal and adult ovaries
Authors: Vazakidou Paraskevi , Evangelista Sara , Li Tianyi , Lecante Laetitia L. , Rosenberg Kristine , Koekkoek Jacco , Salumets Andres , Velthut-Meikas Agne , Damdimopoulou Pauliina , Mazaud-Guittot Séverine , Fowler Paul A. , Leonards Pim E.G. , van Duursen Majorie B.M.
Published: May 2024

Background

Reproduction in women is at risk due to exposure to chemicals that can disrupt the endocrine system during different windows of sensitivity throughout life. Steroid hormone levels are fundamental for the normal development and function of the human reproductive system, including the ovary. This study aims to elucidate steroidogenesis at different life-stages in human ovaries.

Methods

We have developed a sensitive and specific LC-MS/MS method for 21 important steroid hormones and measured them at different life stages: in media from cultures of human fetal ovaries collected from elective terminations of normally progressing pregnancy and in media from adult ovaries from Caesarean section patients, and follicular fluid from women undergoing infertility treatment. Statistically significant differences in steroid hormone levels and their ratios were calculated with parametric tests. Principal component analysis (PCA) was applied to explore clustering of the ovarian-derived steroidogenic profiles.

Results

Comparison of the 21 steroid hormones revealed clear differences between the various ovarian-derived steroid profiles. Interestingly, we found biosynthesis of both canonical and “backdoor” pathway steroid hormones and corticosteroids in first and second trimester fetal and adult ovarian tissue cultures. 17α-estradiol, a less potent naturally occurring isomer of 17β-estradiol, was detected only in follicular fluid. PCA of the ovarian-derived profiles revealed clusters from: adult ovarian tissue cultures with relatively high levels of androgens; first trimester and second trimester fetal ovarian tissue cultures with relatively low estrogen levels; follicular fluid with the lowest androgens, but highest corticosteroid, progestogen and estradiol levels. Furthermore, ratios of specific steroid hormones showed higher estradiol/ testosterone and estrone/androstenedione (indicating higher CYP19A1 activity, p < 0.01) and higher 17-hydroxyprogesterone/progesterone and dehydroepiandrosterone /androstenedione (indicating higher CYP17A1 activity, p < 0.01) in fetal compared to adult ovarian tissue cultures.

Conclusions

Human ovaries demonstrate de novo synthesis of non-canonical and “backdoor” pathway steroid hormones and corticosteroids. Elucidating the steroid profiles in human ovaries improves our understanding of physiological, life-stage dependent, steroidogenic capacity of ovaries and will inform mechanistic studies to identify endocrine disrupting chemicals that affect female reproduction.
Comparing factors associated with overall satisfaction for different forms of remote breastfeeding support in the UK
Authors: Thomson Gill , Balaam Marie-Clare , Tishkovskaya Svetlana
Published: May 2024

Background

Remote forms of breastfeeding support, such as helplines and social media, offer a flexible and convenient form of support to offer help at critical points, e.g., when the risk of breastfeeding cessation is high. Currently, there is little known about who accesses different forms of remote breastfeeding support and what factors impact overall satisfaction. As part of an evaluation of the UK National Breastfeeding Helpline (NBH) (which offers breastfeeding support via a helpline and online media), we aimed to (a) understand who accesses different forms of NBH support, and (b) identify key factors associated with overall satisfaction for helpline and online media support.

Methods

All service users who contacted the NBH between November 2021 and March 2022 were invited to participate in the evaluation via an online survey. Survey questions explored the type and timing of support, reasons for the contact, attitudes towards the help and support received, impact of the support on breastfeeding experiences and demographic factors. Chi-squared and Mann–Whitney tests explored variations in who accessed the helpline or online media. Multiple linear regression models were fitted to explore the factors related to the service users’ ‘overall satisfaction’. The quantitive data were combined with qualitative comments into descriptive themes.

Results

Overall, online media users were significantly more likely to be younger, White, multiparous, less educated and have English as a first language compared to those who contact the helpline. Similar factors that significantly influenced overall satisfaction for both support models were the service being easy to access, receiving helpful information that met expectations, resolving breastfeeding issues, and feeling reassured and more confident. Significant factors for the helpline were callers feeling understood and more knowledgeable about breastfeeding following the call, being able to put into practice the information provided, feeling encouraged to continue breastfeeding, feeling that the volunteer gave the support that was needed, and seeking out additional support.

Conclusions

Online and helpline forms of breastfeeding support suit different demographics and call purposes. While optimal breastfeeding support needs to be accessible, flexible and instrumental, helpline users need real-time relational support to deal with more complex challenges.