bluuebunny/crossref_metadata_2025 huggingface dataset:
Establishing the Kidney dIsease in the National guarD (KIND) registry: an opportunity for epidemiological and clinical research in Saudi Arabia
Authors: Tawhari Mohammed , Alhamadh Moustafa , Alhabeeb Abdulrahman , Ureeg Abdulaziz , Alghnam Suliman , Alhejaili Fayez , Alnasser Lubna A. , Sayyari Abdullah
Published: February 2024

Background

In Saudi Arabia (SA), there has been an alarming increase in the prevalence of chronic kidney diseases (CKD) over the last three decades. Despite being one of the largest countries in the Middle East, renal conditions remain understudied, and there is limited data on their epidemiology and outcomes in SA.

Objectives

To document the experience of establishing a local renal registry assessing the epidemiology of CKD and identifying potential areas for improving the quality and delivery of care for CKD patients.

Methods

This is a multi-center retrospective registry. Potential participants were identified through the ICD-10 codes from five hospitals serving the National Guard affiliates in SA. Patients aged ≥ 18 years treated in any National Guard hospital since 2010 for glomerulonephritis, CKD, or received hemodialysis, peritoneal dialysis, or renal transplant were enrolled. Once enrolled in the registry, patients were followed to the last visit date. RedCap was used to create and host the online registry platform.

Results

A total of 2,912 patients were included, and more than half were younger than 60 years old. Two-thirds of the patients were overweight (25%) or obese (37%). Glomerulonephritis was diagnosed in 10% of the patients, and dialysis-dependent and kidney transplant patients accounted for 31.4% and 24.4%, respectively. Hypertension and diabetes mellitus were detected among 52% and 43% of the participants, respectively. Hemodialysis was the most prevalent dialysis method, with patients spending 3.6 ± 0.4 h per session to receive this treatment. One in every five participants had a kidney biopsy taken (21%). Several barriers and facilitators of the success of this registry were identified.

Conclusions

The KIND registry provides much-needed information about CKD in Saudi Arabia and serves as a model for future projects investigating the natural history and progression of the spectrum of renal diseases. Logistic and financial challenges to the sustainability of registries are identified and discussed.
Differential expression of Semaphorin-7A /CD163-positive macrophages in large artery and cardiogenic stroke
Authors: Jiang Yi , Sun Zhichao , Ge Zhonglin , Tao Zhonghai , Liu Mengqian , Zhong Wen , Dong Nan , Xu Lei , Wang Hui , Xu Yiwen , Shen Xiaozhu
Published: February 2024

Background

Identification of the causes of stroke of undetermined etiology, specifically cardioembolism (CE) and non-CE causes, can inform treatment planning and prognosis prediction. The objective of this study was to analyze the disparities in thrombus composition, particularly Semaphorin-7A (Sema7A) and CD163, between patients diagnosed with large-artery atherosclerosis (LAA) and those with CE, and to investigate their potential association with prognosis.

Methods

Thrombi were collected from patients who underwent mechanical thrombectomy at two hospitals. The patients were categorized into two groups: LAA and CE. We compared the levels of Sema7A and CD163 between these groups and analyzed their relationships with stroke severity, hemorrhagic transformation and prognosis.

Results

The study involved a total of 67 patients. Sema7A expression was found to be significantly higher in the CE group compared to LAA (p < 0.001). Conversely, no statistically significant differences were observed for CD163 between the groups. The presence of Sema7A/CD163 did not show any associations with stroke severity or hemorrhagic transformation (all p > 0.05). However, both Sema7A (OR, 2.017; 95% CI, 1.301–3.518; p = 0.005) and CD163 (OR, 2.283; 95% CI, 1.252–5.724; p = 0.03) were associated with the poor prognosis for stroke, after adjusting for stroke severity.

Conclusion

This study highlights that CE thrombi exhibited higher levels of Sema7A expression compared to LAA thrombi. Moreover, we found a positive correlation between Sema7A/CD163 levels and the poor prognosis of patients with acute ischemic stroke.
Predictive factors of perinatal depression among women with gestational diabetes mellitus in the UAE: a cross-sectional clinical study
Authors: Alzarooni Khadija I. , Abusnana Salah , Zakaria Hala , Hussein Amal , Mussa Bashair M. , Mohammed Ghada
Published: February 2024

Background

Gestational Diabetes Mellitus (GDM) is responsible for the development of 30–50% of type 2 diabetes mellitus that predisposes later to adverse consequences among affected mothers and their offspring. Several studies have suggested that GDM increases the risk of developing perinatal depression (PND); however, factors that are involved in this association are yet to be determined. This study aims to identify factors that interrelate GDM and PND among pregnant and postnatal women in the United Arab Emirates (UAE).

Methods

A total of 186 women between 18 and 45 years old attending the obstetrics clinic during their 3rd trimester or up to 6 months postnatal were recruited between October 2021 and April 2022. Women who were known to have pre-existing diabetes mellitus (type 1 or type 2), kidney disease, liver disease, and those receiving hormonal therapy were excluded. Participants completed a structured questionnaire including sociodemographic data and the Edinburgh Postnatal Depression Scale (EPDS). Based on their EPDS scores, study participants were categorized into three groups: no depression (> 9), possible depression (9–11), and high possibility/strong positive depression (≥ 12). SPSS 26 was used for data analysis.

Results

Among the 186 participants, 81% (n = 151) were Emirati, 41% (n = 76) had no GDM, and 58% (n = 110) had GDM. Of the study participants, 34.4% had a high possibility of strong positive depression, 40.9% had possible depression, and only 6.5% had no depression. The association between GDM and PND was clinically and statistically insignificant, with a calculated odds ratio (OR) of 1.574 (p value = 0.204) and a 95% confidence interval (0.781—3.172). However, age, personal history of depression, and BMI were found to be strong predictors of depression among pregnant/postpartum women in the UAE.

Conclusions

The study findings propose that age, personal history of depression, and obesity are strong predictors of depression during pregnancy. The strong correlation between obesity (which is a known strong predictor of GDM) and PND suggests that further studies with longitudinal designs and longer observational periods might better reveal the relationship between GDM and PND.

Trial registration

Retrospectively registered study by Research Ethics Committees of the University Hospital Sharjah and the University of Sharjah (Ref. No.: UHS-HERC- 025–17122019) December 17, 2019.
Transcriptomics analysis revealed that TAZ regulates the proliferation of KIRC cells through mitophagy
Authors: He Zhen , Shi Jianxi , Zhu Bing , Tian Zhentao , Zhang Zhihong
Published: February 2024

Transcriptional Co-Activator with PDZ-Binding Motif (TAZ, also known as WWTR1) is a downstream effector of the Hippo pathway, involved in the regulation of organ regeneration and cell differentiation in processes such as development and regeneration. TAZ has been shown to play a tumor-promoting role in various cancers. Currently, many studies focus on the role of TAZ in the process of mitophagy. However, the molecular mechanism and biological function of TAZ in renal clear cell carcinoma (KIRC) are still unclear. Therefore, we systematically analyzed the mRNA expression profile and clinical data of KIRC in The Cancer Genome Atlas (TCGA) dataset. We found that TAZ expression was significantly upregulated in KIRC compared with normal kidney tissue and was closely associated with poor prognosis of patients. Combined with the joint analysis of 36 mitophagy genes, it was found that TAZ was significantly negatively correlated with the positive regulators of mitophagy. Finally, our results confirmed that high expression of TAZ in KIRC inhibits mitophagy and promotes KIRC cell proliferation. In conclusion, our findings reveal the important role of TAZ in KIRC and have the potential to be a new target for KIRC therapy.
Ocular parameters associated with visual performance of enhanced monofocal intraocular lens
Authors: Kim Da Ran , Yoon Young Chae , Whang Woong-Joo , Hwang Ho Sik , Na Kyung-Sun
Published: February 2024

Background

An enhanced monofocal intraocular lenses (IOLs) (Tecnis Eyhance ICB00 and Tecnis Eyhance Toric DIU) has been developed to enhance intermediate vision while avoiding the disadvantages of multifocal IOLs. Although many studies have demonstrated the improvement of intermediate visual acuity with enhanced monofocal IOLs, it is not known specifically for which patients these IOLs should be recommended or avoided. In this study, we aim to find out which ocular parameters affect vision performance and photic phenomenon of ICB00 or DIU at different distances.

Methods

Patients who underwent cataract surgery with ICB00 or DIU, performed by a single surgeon, were included. Before surgery, the patients’ age, gender, axial length, anterior chamber depth, spherical aberration Z (4,0), vertical coma, horizontal coma, angle kappa (κ), angle alpha (α), and other ocular parameters were investigated. One month after surgery, uncorrected near visual acuity (UNVA at 40 cm), uncorrected intermediate visual acuity (UIVA at 66 cm), uncorrected distance logMAR visual acuity (UDVA), IOL decentration, and quality of vision (QoV) questionnaires were conducted.

Results

A total of 43 patients (58 eyes) were included. The results of the univariate linear regression analyses showed a negative correlation between spherical aberration and logMAR UNVA and UIVA (p = 0.003, β=-0.51 and p = 0.018, β=-0.23, respectively) and a positive correlation between angle α and logMAR UIVA (p = 0.036, β = 0.19). Deeper anterior chamber depth (ACD) was associated with poorer total QoV (p = 0.018, β = 14.43), particularly in glare, halo, blur, and fluctuation perception. A higher degree of IOL decentration tended to decrease UNVA and UIVA (Pearson correlation coefficient, r = 0.336 and r = 0.221, respectively); however, no significant effect was observed on UDVA (Pearson correlation coefficient, r = 0.042).

Conclusions

In enhanced monofocal IOLs, a higher level of spherical aberration is associated with better performance in UNVA and UIVA, whereas a larger angle α has a negative impact. A deeper ACD negatively affects the QoV.
The association between sex and neonatal respiratory distress syndrome
Authors: Fang Keren , Yue Shaojie , Wang Shuo , Wang Mingjie , Yu Xiaohe , Ding Ying , Lv Mei , Liu Yang , Cao Chuanding , Liao Zhengchang
Published: February 2024

Background

To investigate the association between sex and neonatal respiratory distress syndrome (NRDS).

Methods

Neonates born at our hospital and transferred to the neonatal department within 1 h were retrospectively analyzed. Depending on whether they developed NRDS during their hospital stay, the neonates was divided into NRDS and non-NRDS groups. There were 142 neonates in the NRDS group (95 males and 47 females) and 310 neonates in the non-NRDS group (180 males and 140 females). The neonates’ data on gestational age (GA), sex, birth weight, white blood cell count (WBC), platelet count (PLT), C-reactive protein (CRP), total immunoglobulin M (total IgM), gestational diabetes mellitus(GDM), antenatal steroids use, meconium-stained amniotic fluid, and preterm premature rupture of membranes(PPROM) were gathered.

Results

452 neonates (265 males and 187 females) were involved for the purpose of collecting basic characteristic. Multivariate analysis, males had a 1.87 times higher risk of NRDS than females (P < 0.05) after controlling for the confounding effects of GA, birth weight, WBC, PLT, CRP, total IgM, GDM, antenatal steroids use, meconium-stained amniotic fluid, and PPROM.

Conclusions

Sex was associated with NRDS; males had a considerably higher risk of NRDS than females.
A prospective study to evaluate the contribution of the pediatric appendicitis score in the decision process
Authors: Vevaud Kevin , Dallocchio Aymeric , Dumoitier Nathalie , Laspougeas Alban , Labrunie Anaïs , Belgacem Alexis , Fourcade Laurent , Ballouhey Quentin
Published: February 2024

Background

The objective of this study was to assess the likelihood of acute appendicitis (AA) in children presenting with abdominal symptoms at the emergency department (ED), based on their prior primary care (PC) consultation history.

Methods

Between February and June 2021, we prospectively enrolled all children presenting at the ED with acute abdominal pain indicative of possible acute appendicitis (AA). Subsequently, they were categorized into three groups: those assessed by a PC physician (PG), those brought in by their family without a prior consultation (FG), and those admitted after a PC consultation without being assessed as such. The primary objective was to assess the probability of AA diagnosis using the Pediatric Appendicitis Score (PAS). Secondary objectives included analyzing PAS and C-reactive protein (CRP) levels based on the duration of pain and final diagnoses.

Results

124 children were enrolled in the study (PG, n = 56; FG, n = 55; NG, n = 13). Among them, 29 patients (23.4%) were diagnosed with AA, with 13 cases (23.2%) from the PG and 14 cases (25.4%) from the FG. The mean PAS scores for AA cases from the PG and FG were 6.69 ± 1.75 and 7.57 ± 1.6, respectively, (p = 0.3340). Both PAS scores and CRP levels showed a significant correlation with AA severity. No cases of AA were observed with PAS scores < 4.

Conclusions

There was no significant difference in PAS scores between patients addressed by PG and FG, even though PAS scores tended to be higher for patients with AA. We propose a new decision-making algorithm for PC practice, which incorporates inflammatory markers and pain duration.

Trial registration

Institutional Ethics Committee registration number: 447-2021-103 (10/01/2021).

Clinical trials registration number

ClinicalTrials.gov Identifier: NCT04885335 (Registered on 13/05/2021).
The sexual and reproductive healthcare challenges when dealing with female migrants and refugees in low and middle-income countries (a qualitative evidence synthesis)
Authors: Darebo Tadele Dana , Spigt Mark , Teklewold Berhanetsehay , Badacho Abebe Sorsa , Mayer Niklas , Teklewold Meba
Published: February 2024

Background

Migrants and refugees face unprecedented inequalities in accessing sexual and reproductive health (SRH) in developed and developing countries. Most attention has focused on the rich world perspective, while there are huge numbers of migrants and refugees moving towards less developed countries. This article synthesizes the barriers to proper SRH care from low and middle-income countries perspective.

Methods

We performed a systematic review of articles containing primary source qualitative and quantitative studies with thick qualitative descriptions. Articles from various databases, including PubMed, Science Direct, HINARI, and Google Scholar, published between 2012 and 2022 were included. Because the context differed, we excluded articles dealing with migrants and refugees from low- and middle-income countries living in high-income countries. To select articles, a preferred reporting item for systematic reviews and meta-analyses (PRISMA) was used. The articles’ quality was assessed using the standard QASP checklist. We used a socio-ecological model to investigate barriers at various levels, and thematic analysis was used to identify the strongest themes at each level of the model. This synthesis is registered under PROSPERO number CRD42022341460.

Results

We selected fifteen articles from a total of 985 for the final analysis. The results show that despite the diversity of the participants’ homes and countries of origin, their experiences using SRH services were quite similar. Most female migrants and refugees claimed to have encountered discrimination from service providers, and linguistic and cultural obstacles played a significant role in their experiences. In nations lacking universal healthcare coverage, the cost of care was a barrier to the use of SRH services. Other main obstacles to using SRH services were a lack of knowledge about these programs, worries about privacy, inadequate communication, stigma in the community, and gender-related power imbalances.

Conclusion

To enhance the use of SRH by female migrants and refugees, it is vital to provide person-centered care and involve husbands, parents, in-laws, and communities in SRH coproduction. Training on cultural competency, compassion, and respect must be provided to healthcare personnel. Increasing financial access for migrant and refugee healthcare is crucial, as is meeting their basic requirements.
The prediction of influenza-like illness using national influenza surveillance data and Baidu query data
Authors: wei Su , Lin Sun , wenjing Zhao , Shaoxia Song , Yuejie Yang , Yujie He , Shu Zhang , Zhong Li , Ti Liu
Published: February 2024

Background

Seasonal influenza and other respiratory tract infections are serious public health problems that need to be further addressed and investigated. Internet search data are recognized as a valuable source for forecasting influenza or other respiratory tract infection epidemics. However, the selection of internet search data and the application of forecasting methods are important for improving forecasting accuracy. The aim of the present study was to forecast influenza epidemics based on the long short-term memory neural network (LSTM) method, Baidu search index data, and the influenza-like-illness (ILI) rate.

Methods

The official weekly ILI% data for northern and southern mainland China were obtained from the Chinese Influenza Center from 2018 to 2021. Based on the Baidu Index, search indices related to influenza infection over the corresponding time period were obtained. Pearson correlation analysis was performed to explore the association between influenza-related search queries and the ILI% of southern and northern mainland China. The LSTM model was used to forecast the influenza epidemic within the same week and at lags of 1–4 weeks. The model performance was assessed by evaluation metrics, including the mean square error (MSE), root mean square error (RMSE) and mean absolute error (MAE).

Results

In total, 24 search queries in northern mainland China and 7 search queries in southern mainland China were found to be correlated and were used to construct the LSTM model, which included the same week and a lag of 1–4 weeks. The LSTM model showed that ILI% + mask with one lag week and ILI% + influenza name were good prediction modules, with reduced RMSE predictions of 16.75% and 4.20%, respectively, compared with the estimated ILI% for northern and southern mainland China.

Conclusions

The results illuminate the feasibility of using an internet search index as a complementary data source for influenza forecasting and the efficiency of using the LSTM model to forecast influenza epidemics.
Physical activity and odds of coronary heart disease among Lebanese women
Authors: Ghaddar Fatima , Zeidan Rouba K , Salameh Pascale , Maupas-Schwalm Françoise
Published: February 2024

Background

It is known that physical activity (PA) is protective against cardiovascular morbidity and mortality. However, few studies have examined the association between PA, sedentary lifestyle and coronary heart disease (CHD) in women. This case–control study investigates the relationship between PA and sedentary behavior on CHD odds in Lebanese women over forty.

Methods

One thousand five hundred selected Lebanese women (300 cases and 1200 controls) were included between 2018–2019. Cases were hospitalized women newly diagnosed with CHD, whereas the control groups were free of any heart diseases. Data on socio-demographic, lifestyle, cardiovascular factors, PA and sedentary lifestyle were collected. Multivariate logistic regressions, adjusted for covariates, were performed to investigate the association of PA domains and sedentary behavior with CHD.

Results

A sedentary lifestyle combined with low activity levels increased the odds of CHD. Among cases, 46.7% participated in moderate or vigorous PA against almost 60.3% of controls. 36.3% of coronary patients had more than 10 h/day of sedentary time, with a positive correlation with CHD (adjusted OR: 1.533, 95%CI: 1.046–2.247). Conversely, moderate and high levels (respectively 600–3000 and ≥ 3000 metabolic equivalents [MET]-minutes/week) of domestic/garden PA revealed lower CHD odds (OR: 0.566, 95%CI: 0.396–0.808 and 0.193, 0.065–0.578 respectively). The detrimental influence of sedentary lifestyle appeared to be significantly reversed by weekly moderate PA, especially as weekly sedentary time was less (OR: 0.616, 95%CI: 0.427–0.888/ 6 to10h of sedentary time and OR: 0.537, 95% CI: 0.37–0.779/ ≤ 6 h), and except sedentary time exceeding 10 h daily. Two PA patterns revealed lower CHD odds: transport-related and domestic/garden PA, as early as low amount, even after adjustment for possible confounders.

Conclusion

The current study highlights the importance of combating sedentary behaviors and engaging in regular, easily accessible PA to reduce the odds of coronary disease among aging women. Therefore, better information regarding the benefits of physical activities such as transportation-related activities or gardening would be helpful in enhancing the prevention of CHD in aging women.
Plastic and elastic biomechanical properties of anterior cruciate ligament autografts
Authors: Garcia Mason , Momenzadah Kaveh , Shariyate Mohammad Javad , Kheir Nadim , Khak Mohammad , Villarreal Juan B , Abbasian Mohammadreza , Flaherty Alexandra F , Hanna Philip , Ramappa Arun , Paschos Nikolaos K , Nazarian Ara
Published: February 2024

Background

Anterior cruciate ligament (ACL) rupture is a common orthopedic injury, occurring in roughly 68.6 per 100,000 persons annually, with the primary treatment option being ACL reconstruction. However, debate remains about the appropriate graft type for restoring the native biomechanical properties of the knee. Furthermore, plastic graft elongation may promote increased knee laxity and instability without rupture. This study aims to investigate the plastic properties of common ACL-R graft options.

Methods

Patellar tendon (PT), hamstring tendon (HT), and quadriceps tendon (QT) grafts were harvested from 11 cadaveric knees (6 male and 5 female) with a mean age of 71(range 55–81). All grafts were mechanically tested under uniaxial tension until failure to determine each graft’s elastic and plastic biomechanical properties.

Results

Mechanically, the QT graft was the weakest, exhibiting the lowest failure force and the lowest failure stress (QT < HT, p = 0.032). The PT was the stiffest of the grafts, having a significantly higher stiffness (PT > QT, p = 0.0002) and Young’s modulus (PT > QT, p = 0.001; PT > HT, p = 0.041). The HT graft had the highest plastic elongation at 4.01 ± 1.32 mm (HT > PT, p = 0.002). The post-yield behavior of the HT tendon shows increased energy storage capabilities with the highest plastic energy storage (HT > QT, p = 0.012) and the highest toughness (HT > QT, p = 0.032).

Conclusion

Our study agrees with prior studies indicating that the failure load of all grafts is above the requirements for everyday activities. However, grafts may be susceptible to yielding before failure during daily activities. This may result in the eventual loss of functionality for the neo-ACL, resulting in increased knee laxity and instability.
Anti-bacterial and anti-inflammatory properties of Vernonia arborea accelerate the healing of infected wounds in adult Zebrafish
Authors: Vaidyanathan Lalitha , Lokeswari T. Sivaswamy
Published: February 2024

Background

Management of wounds and healing under impaired conditions are the major challenges faced globally by healthcare workers. Phytocompounds which are anti-microbial and capable of modulating inflammation contribute to overall wound healing and regain of the lost structure and function especially in wounds impaired with polymicrobial infection.

Methods

An acute cutaneous impaired wound model using adult zebrafish was validated to simulate mammalian wound pathophysiology. This model was used to evaluate phytofractions of Vernonia arborea in the present study, for reduction of infection; myeloperoxidase (MPO) as a marker of infection; neutrophil infiltration and resolution; kinetics of inflammatory cytokines; and wound repair kinetics (viz., nitrite levels and iNoS expression; reepithelisation).

Results

Four fractions which were active in-vitro against five selected wound microbes were shown to reduce ex-vivo microbial bioburden upto 96% in the infected wound tissue. The reduction in CFU correlated with the neutrophil kinetics and MPO enzyme levels in the treated, wound infected zebrafish. Expression of pro-inflammatory cytokines (IL-6 and TNF-α) was downregulated while upregulating anti-inflammatory cytokine (IL-10), and nitric oxide signalling with fourfold increase in iNOS expression. The adult zebrafish wound model could well serve as a standard tool for assessing phytoextracts such as V. arborea for wound healing with anti-microbial properties.

Graphical Abstract
The bumpy ride to a medical PhD degree: a qualitative study on factors influencing motivation
Authors: den Bakker C. R. , Ommering B. W. C. , de Beaufort A. J. , Dekker F. W. , Bustraan J.
Published: February 2024

Introduction

In parallel with a tremendous increase in medical PhD enrolments, concerns have risen about PhD candidates’ poor well-being, increasing attrition rates for PhD programmes, and, eventually, a decline in clinician-scientists. According to the Self-Determination Theory, autonomous motivation is strongly linked to positive aspects of well-being and other positive outcomes such as study completion and success. In this way, motivation has a pivotal role in successful completion of medical doctoral programmes. In this study we explored factors affecting motivation during the PhD journey and aimed to contribute to engaging doctoral education environments, and, eventually, a sustainable clinician-scientist workforce.

Methods

This constructivist qualitative interview study was conducted among ten medical PhD candidates in the final phase of their PhD. We used timeline assisted interviews to identify meaningful experiences throughout their PhD journey. Thematic analyses as an iterative process resulted in overarching themes.

Results

We identified six themes influencing autonomous and controlled motivation along the challenging PhD journey: (1) Initial motivation to start a PhD matters; (2) Autonomy as a matter of the right dose at the right time; (3) PhD as proof of competence and/or learning trajectory?; (4) It takes two to tango; (5) Peers can make or break your PhD; (6) Strategies to stay or get back on track.

Conclusion

This study revealed factors that contribute positively and/or negatively to autonomous and controlled motivation. Some factors impacted motivation differently depending on the PhD phase and individual strategies. Additionally, some factors could coincide and change from positive to negative and vice versa, showing that a successful journey cannot simply be reduced to an absence of negative experiences.
Dutch dismissal practices: characteristics, consequences, and contrasts in residents’ case law in community-based practice versus hospital-based specialties
Authors: Godschalx-Dekker Judith , van Mook Walther
Published: February 2024

Background

In the Netherlands, 2 to 10% of the residents terminate training prematurely. Infrequently, termination of training is by dismissal. Incidentally, residents may disagree, dispute and challenge these decisions from the programme directors. Resident dismissal is always a difficult decision, most commonly made after, repeated assessments, and triangulation of the resulting assessment data and one or more remediation attempts. Nevertheless, the underlying reasons for dismissal and the policies for remediation and dismissal may differ between training programmes. Such differences may however impact the chance of remediation success, the chance of dismissal and subsequent residents’ appeals.

Method

We included a total of 70 residents from two groups (community-based and hospital-based specialties) during 10 years of appeals. Subsequently, we compared these groups on factors potentially associated with the outcome of the conciliation board decision regarding the residents’ dismissal. We focused herein on remediation strategies applied, and reasons reported to dismiss residents.

Results

In both groups, the most alleged reason to dismiss residents was lack of trainability, > 97%. This was related to deficiencies in professionalism in community-based practice and medical expertise in hospital-based specialties respectively. A reason less frequently mentioned was endangerment of patient care, < 26%. However, none of these residents accused of endangerment, actually jeopardized the patients’ health, probably due to the vigilance of their supervisors. Remediation strategies varied between the two groups, whereas hospital-based specialties preferred formal remediation plans in contrast to community-based practice. A multitude of remediation strategies per competency (medical expertise, professionalism, communication, management) were applied and described in these law cases.

Discussion

Residents’ appeals in community-based practice were significantly less likely to succeed compared to hospital-based specialties. Hypothesised explanatory factors underlying these differences include community-based practices’ more prominent attention to the longitudinal assessment of professionalism, the presence of regular quarterly progress meetings, precise documentation of deficiencies, and discretion over the timing of dismissal in contrast to dismissal in the hospital-based specialties which is only formally possible during scheduled formal summative assessment meetings.
Inhaler use technique course: an effective postgraduate training solution for pharmacists to enhance therapeutic outcomes as part of patient education
Authors: Guzenda Weronika , Żabiński Jerzy , Plewka Beata , Byliniak Michał , Przymuszała Piotr , Dąbrowiecki Piotr , Michalak Michał , Waszyk-Nowaczyk Magdalena
Published: February 2024

Background

Patients with asthma and chronic obstructive pulmonary disease could benefit from education on using inhalers provided by pharmacists. However, pharmacists may have limited competencies, indicating the necessity to implement appropriate postgraduate courses. The study aimed to evaluate an inhaler use course for pharmacists, including its impact on participants’ knowledge and satisfaction.

Methods

The study involved 261 pharmacists from community pharmacies and was conducted between September 2019 and March 2021. A pre-post analysis of their knowledge of the topic was applied. Additionally, at the beginning of the course, participants were asked about their educational needs, and at the end, they completed a satisfaction survey. The preferred learning formats indicated by participants were interactive workshops and lectures.

Results

As a result of the course, both their actual and self-assessed level of knowledge significantly increased. The percentage of correct answers in the test before the training was 24.4%, while after, it was 84.3% (p < 0.0001). Before the course, their average self-assessed level of knowledge was 52.0%, and after the training, it increased to 90.0% (p < 0.0001). Almost all respondents stated that the course met their expectations. They estimated their satisfaction at 94.0% and the usefulness of the provided information at 98.0%.

Conclusions

Improved preparation of pharmacists resulting from their participation in the course can contribute to providing more professional advice to patients, thereby positively influencing the pharmaceutical care process in community pharmacies.
The role of bioethics services in paediatric intensive care units: a qualitative descriptive study
Authors: Alexander Denise , Quirke Mary , Greene Jo , Cassidy Lorna , Hilliard Carol , Brenner Maria
Published: February 2024

Background

There is considerable variation in the functionality of bioethical services in different institutions and countries for children in hospital, despite new challenges due to increasing technology supports for children with serious illness and medical complexity. We aimed to understand how bioethics services address bioethical concerns that are increasingly encountered in paediatric intensive care.

Methods

A qualitative descriptive design was used to describe clinician’s perspectives on the functionality of clinical bioethics services for paediatric intensive care units. Clinicians who were members of formal or informal clinical bioethics groups, or who were closely involved with the process of working through ethically challenging decisions, were interviewed. Interviews took place online. Resulting transcripts were analysed using thematic analysis.

Results

From 33 interviews, we identified four themes that described the functionality of bioethics services when a child requires technology to sustain life: striving for consensus; the importance of guidelines; a structure that facilitates a time-sensitive and relevant response; and strong leadership and teamwork.

Conclusions

Clinical bioethics services have the potential to expand their role due to the challenges brought by advancing medical technology and the increasing options it brings for treatment. Further work is needed to identify where and how bioethics services can evolve and adapt to fully address the needs of the decision-makers in PICU.
Implementation of advance care planning in the routine care for acutely admitted patients in geriatric units: protocol for a cluster randomized controlled trial
Authors: Romøren Maria , Hermansen Karin Berg , Sævareid Trygve Johannes Lereim , Brøderud Linn , Westbye Siri Færden , Wahl Astrid Klopstad , Thoresen Lisbeth , Rostoft Siri , Førde Reidun , Ahmed Marc , Aas Eline , Midtbust May Helen , Pedersen Reidar
Published: February 2024

Background

Acutely ill and frail older adults and their next of kin are often poorly involved in treatment and care decisions. This may lead to either over- or undertreatment and unnecessary burdens. The aim of this project is to improve user involvement and health services for frail older adults living at home, and their relatives, by implementing advance care planning (ACP) in selected hospital wards, and to evaluate the clinical and the implementation interventions.

Methods

This is a cluster randomized trial with 12 hospital units. The intervention arm receives implementation support for 18 months; control units receive the same support afterwards. The ACP intervention consists of 1. Clinical intervention: ACP; 2. Implementation interventions: Implementation team, ACP coordinator, network meetings, training and supervision for health care personnel, documentation tools and other resources, and fidelity measurements with tailored feedback; 3. Implementation strategies: leadership commitment, whole ward approach and responsive evaluation. Fidelity will be measured three times in the intervention arm and twice in the control arm. Here, the primary outcome is the difference in fidelity changes between the arms. We will also include 420 geriatric patients with one close relative and an attending clinician in a triadic sub-study. Here, the primary outcomes are quality of communication and decision-making when approaching the end of life as perceived by patients and next of kin, and congruence between the patient’s preferences for information and involvement and the clinician’s perceptions of the same. For patients we will also collect clinical data and health register data. Additionally, all clinical staff in both arms will be invited to answer a questionnaire before and during the implementation period. To explore barriers and facilitators and further explore the significance of ACP, qualitative interviews will be performed in the intervention units with patients, next of kin, health care personnel and implementation teams, and with other stakeholders up to national level. Lastly, we will evaluate resource utilization, costs and health outcomes in a cost-effectiveness analysis.

Discussion

The project may contribute to improved implementation of ACP as well as valuable knowledge and methodological developments in the scientific fields of ACP, health service research and implementation science.

Trial registration

ClinicalTrials.gov Identifier NCT05681585. Registered 03.01.23.
Newborn and child health national and provincial clinical practice guidelines in South Africa, Nigeria and Malawi: a scoping review
Authors: Mthethwa Mashudu , Mbeye Nyanyiwe Masingi , Effa Emmanuel , Arikpo Dachi , Blose Ntombifuthi , Brand Amanda , Chibuzor Moriam , Chipojola Roselyn , Durao Solange , Esu Ekpereonne , Kallon Idriss Ibrahim , Kunje Gertrude , Lakudzala Suzgika , Naude Celeste , Leong Trudy D. , Lewin Simon , Mabetha Denny , McCaul Michael , Meremikwu Martin , Vandvik Per Olav , Kredo Tamara
Published: February 2024

Background

Low and middle-income countries remain disproportionately affected by high rates of child mortality. Clinical practice guidelines are essential clinical tools supporting implementation of effective, safe, and cost-effective healthcare. High-quality evidence-based guidelines play a key role in improving clinical management to impact child mortality. We aimed to identify and assess the quality of guidelines for newborn and child health published in South Africa, Nigeria and Malawi in the last 5 years (2017–2022).

Methods

We searched relevant websites (June–July 2022), for publicly available national and subnational de novo or adapted guidelines, addressing newborn and child health in the three countries. Pairs of reviewers independently extracted information from eligible guidelines (scope, topic, target population and users, responsible developers, stakeholder consultation process, adaptation description, assessment of evidence certainty). We appraised guideline quality using the Appraisal of Guidelines for Research & Evaluation (AGREE II) instrument.

Results

We identified 40-guidelines from the three countries. Of these, 8/40 reported being adopted from a parent guideline. More guidelines (n = 19) provided guidance on communicable diseases than on non-communicable diseases (n = 8). Guidelines were most often developed by national health ministries (n = 30) and professional societies (n = 14). Eighteen guidelines reported on stakeholder consultation; with Nigeria (10/11) and Malawi (3/6) faring better than South Africa (5/23) in reporting this activity. The Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) approach was used in 1/7 guidelines that reported assessing certainty of evidence. Overall guidelines scored well on two AGREE II domains: scope and purpose median (IQR) score 68% (IQR 47–83), and clarity of presentation 81% (67–94). Domains critical for ensuring credible guidance scored below 20%: rigour of development 11% (4–32) and editorial independence 6% (0–27).

Conclusion

National ministries and professional societies drive guideline activities in Malawi, Nigeria and South Arica. However, the methods and reporting do not adhere to global standards. We found low AGREE II scores for rigour of guideline development and editorial independence and limited use of GRADE or adaptation methods. This undermines the credibility of available guidelines to support evidence-informed care. Our findings highlight the importance of ongoing efforts to strengthen partnerships, capacity, and support for guideline development.
Predicting thresholds for population replacement gene drives
Authors: Janzen Anna , Pothula Ratnasri , Sychla Adam , Feltman Nathan R. , Smanski Michael J.
Published: February 2024

Background

Threshold-dependent gene drives (TDGDs) could be used to spread desirable traits through a population, and are likely to be less invasive and easier to control than threshold-independent gene drives. Engineered Genetic Incompatibility (EGI) is an extreme underdominance system previously demonstrated in Drosophila melanogaster that can function as a TDGD when EGI agents of both sexes are released into a wild-type population.

Results

Here we use a single generation fitness assay to compare the fecundity, mating preferences, and temperature-dependent relative fitness to wild-type of two distinct genotypes of EGI agents. We find significant differences in the behavior/performance of these EGI agents that would not be predicted a priori based on their genetic design. We report a surprising temperature-dependent change in the predicted threshold for population replacement in an EGI agent that drives ectopic expression of the developmental morphogen pyramus.

Conclusions

The single-generation fitness assay presented here could reduce the amount of time required to estimate the threshold for TDGD strategies for which hybrid genotypes are inviable. Additionally, this work underscores the importance of empirical characterization of multiple engineered lines, as behavioral differences can arise in unique genotypes for unknown reasons.
Risk-based lung cancer screening in heavy smokers: a benefit–harm and cost-effectiveness modeling study
Authors: Liu Yin , Xu Huifang , Lv Lihong , Wang Xiaoyang , Kang Ruihua , Guo Xiaoli , Wang Hong , Zheng Liyang , Liu Hongwei , Guo Lanwei , Chen Qiong , Liu Shuzheng , Qiao Youlin , Zhang Shaokai
Published: February 2024

Background

Annual screening through low-dose computed tomography (LDCT) is recommended for heavy smokers. However, it is questionable whether all individuals require annual screening given the potential harms of LDCT screening. This study examines the benefit–harm and cost-effectiveness of risk-based screening in heavy smokers and determines the optimal risk threshold for screening and risk-stratified screening intervals.

Methods

We conducted a comparative cost-effectiveness analysis in China, using a cohort-based Markov model which simulated a lung cancer screening cohort of 19,146 heavy smokers aged 50 ~ 74 years old, who had a smoking history of at least 30 pack-years and were either current smokers or had quit for < 15 years. A total of 34 risk-based screening strategies, varying by different risk groups for screening eligibility and screening intervals (1-year, 2-year, 3-year, one-off, non-screening), were evaluated and were compared with annual screening for all heavy smokers (the status quo strategy). The analysis was undertaken from the health service perspective with a 30-year time horizon. The willingness-to-pay (WTP) threshold was adopted as three times the gross domestic product (GDP) of China in 2021 (CNY 242,928) per quality-adjusted life year (QALY) gained.

Results

Compared with the status quo strategy, nine risk-based screening strategies were found to be cost-effective, with two of them even resulting in cost-saving. The most cost-effective strategy was the risk-based approach of annual screening for individuals with a 5-year risk threshold of ≥ 1.70%, biennial screening for individuals with a 5-year risk threshold of 1.03 ~ 1.69%, and triennial screening for individuals with a 5-year risk threshold of < 1.03%. This strategy had the highest incremental net monetary benefit (iNMB) of CNY 1032. All risk-based screening strategies were more efficient than the status quo strategy, requiring 129 ~ 656 fewer screenings per lung cancer death avoided, and 0.5 ~ 28 fewer screenings per life-year gained. The cost-effectiveness of risk-based screening was further improved when individual adherence to screening improved and individuals quit smoking after being screened.

Conclusions

Risk-based screening strategies are more efficient in reducing lung cancer deaths and gaining life years compared to the status quo strategy. Risk-stratified screening intervals can potentially balance long-term benefit–harm trade-offs and improve the cost-effectiveness of lung cancer screenings.
Neuregulin-1 and ALS19 (ERBB4): at the crossroads of amyotrophic lateral sclerosis and cancer
Authors: Adashek Jacob J. , Pandya Chinmayi , Maragakis Nicholas J. , De Pradip , Cohen Philip R. , Kato Shumei , Kurzrock Razelle
Published: February 2024

Background

Neuregulin-1 (NRG1) is implicated in both cancer and neurologic diseases such as amyotrophic lateral sclerosis (ALS); however, to date, there has been little cross-field discussion between neurology and oncology in regard to these genes and their functions.

Main body

Approximately 0.15–0.5% of cancers harbor NRG1 fusions that upregulate NRG1 activity and hence that of the cognate ERBB3/ERBB4 (HER3/HER4) receptors; abrogating this activity with small molecule inhibitors/antibodies shows preliminary tissue-agnostic anti-cancer activity. Notably, ERBB/HER pharmacologic suppression is devoid of neurologic toxicity. Even so, in ALS, attenuated ERBB4/HER4 receptor activity (due to loss-of-function germline mutations or other mechanisms in sporadic disease) is implicated; indeed, ERBB4/HER4 is designated ALS19. Further, secreted-type NRG1 isoforms may be upregulated (perhaps via a feedback loop) and could contribute to ALS pathogenesis through aberrant glial cell stimulation via enhanced activity of other (e.g., ERBB1-3/HER1-3) receptors and downstream pathways. Hence, pan-ERBB inhibitors, already in use for cancer, may be agents worthy of testing in ALS.

Conclusion

Common signaling cascades between cancer and ALS may represent novel therapeutic targets for both diseases.
Platycodin D2 enhances P21/CyclinA2-mediated senescence of HCC cells by regulating NIX-induced mitophagy
Authors: Sun Lili , Li Yaru , Zhao Renshuang , Fan Qinlei , Liu Fei , Zhu Yilong , Han Jicheng , Liu Yunyun , Jin Ningyi , Li Xiao , Li Yiquan
Published: February 2024

Background

Hepatocellular carcinoma (HCC) cells usually show strong resistance to chemotherapy, which not only reduces the efficacy of chemotherapy but also increases the side effects. Regulation of autophagy plays an important role in tumor treatment. Cell senescence is also an important anti-cancer mechanism, which has become an important target for tumor treatment. Therefore, it is of great clinical significance to find anti-HCC drugs that act through this new mechanism. Platycodin D2 (PD2) is a new saponin compound extracted from the traditional Chinese medicine Platycodon grandiflorum.

Purpose

Our study aimed to explore the effects of PD2 on HCC and identify the underlying mechanisms.

Methods

First, the CCK8 assay was used to detect the inhibitory effect of PD2 on HCC cells. Then, different pathways of programmed cell death and cell cycle regulators were measured. In addition, we assessed the effects of PD2 on the autophagy and senescence of HCC cells by flow cytometry, immunofluorescence staining, and Western blotting. Finally, we studied the in vivo effect of PD2 on HCC cells by using a mouse tumor-bearing model.

Results

Studies have shown that PD2 has a good anti-tumor effect, but the specific molecular mechanism has not been clarified. In this study, we found that PD2 has no obvious toxic effect on normal hepatocytes, but it can significantly inhibit the proliferation of HCC cells, induce mitochondrial dysfunction, enhance autophagy and cell senescence, upregulate NIX and P21, and downregulate CyclinA2. Gene silencing and overexpression indicated that PD2 induced mitophagy in HCC cells through NIX, thereby activating the P21/CyclinA2 pathway and promoting cell senescence.

Conclusions

These results indicate that PD2 induces HCC cell death through autophagy and aging. Our findings provide a new strategy for treating HCC.

Graphical Abstract