bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical and genetic features in autosomal recessive bestrophinopathy in Chinese cohort
Authors: Zhao Dongsheng , Gu Victoria Y. , Wang Yafu , Peng Jie , Lyu Jiao , Fei Ping , Xu Yu , Zhang Xiang , Zhao Peiquan
Published: July 2024

Purpose

To provide a genotype and phenotype characterization of the BEST1 mutation in Chinese patients with autosomal recessive bestrophinopathy (ARB) through multimodal imaging and next-generation sequencing (NGS).

Methods

Seventeen patients from 17 unrelated families of Chinese origin with ARB were included in a retrospective cohort study. Phenotypic characteristics, including anterior segment features, were assessed by multimodal imaging. Multigene panel testing, involving 586 ophthalmic disease-associated genes, and Sanger sequencing were performed to identify disease-causing variants.

Results

Among 17 ARB patients, the mean follow-up was 15.65 months and average onset age was 30.53 years (range: 9–68). Best corrected visual acuity ranged from light perception to 0.8. EOG recordings showed a typically decreased Arden ratio in 12 patients, and a normal or slightly decreased Arden ratio in two patients. Anterior features included shallow anterior chambers (16/17), ciliary pronation (16/17), iris bombe (13/17), iridoschisis (2/17), iris plateau (1/17), narrow angles (16/17) and reduced axial lengths (16/17). Sixteen patients had multiple bilateral small, round, yellow vitelliform deposits distributed throughout the posterior pole, surrounding the optic disc. Initial diagnoses included angle-closure glaucoma (four patients), Best disease (three patients), and central serous chorioretinopathy secondary to choroidal neovascularization (CNV) (one patient), with the remainder diagnosed with ARB. Fourteen patients underwent preventive laser peripheral iridotomy, four of whom also received combined trabeculectomy and iridotomy in both eyes for uncontrolled intraocular pressure. One patient received intravitreal conbercept for CNV. Overall, 15 distinct disease-causing variants of BEST1 were identified, with 14 (82.35%) patients having missense mutations. Common mutations included p. Arg255-256 and p. Ala195Val (both 23.68%), with the most frequent sites in exons 7 and 5.

Conclusions

This study provides a comprehensive characterization of anterior segment and genetic features in ARB, with a wide array of morphological abnormalities. Findings are relevant for refining clinical practices and genetic counseling and advancing pathogenesis research.
Childhood vaccination among Polish immigrants in Norway: a qualitative study
Authors: Gleditsch Rebecca Nybru , Hynek Kamila , Hansen Bo T. , Ofitserova Trine Skogset , Winje Brita Askeland , Skogheim Thea Steen
Published: July 2024

Background

Confidence in childhood vaccination is high in Norway and the Norwegian Childhood Immunization Programme (NCIP) achieves high overall coverage rates. However, lower coverage has been observed for some immigrant groups, including Polish immigrants who represent the largest immigrant group in Norway. Anti-vaccine sentiments and increased refusal of mandatory childhood vaccination has been on the rise in Poland, but it is unknown whether such attitudes also apply to Polish immigrants in Norway, as they experience a different vaccination policy and perhaps also different attitudes to vaccines. This qualitative study aims to explore attitudes towards childhood vaccination in Norway among Polish immigrants.

Methods

We interviewed 15 Polish parents living in Norway in 2022. We recruited the participants by purposive sampling and analyzed the interviews by reflexive thematic analysis.

Results

Three themes were identified: views of childhood vaccination, vaccine hesitancy, and differences in childhood vaccination between Poland and Norway. Overall, the participants favored childhood vaccination and viewed most of the vaccines included in the NCIP as safe and reliable. Human papilloma virus, meningococcal and pneumococcal vaccines were declined by some of the parents. Comparisons of childhood vaccination in Poland and Norway was evident in many of the interviews, especially among parents whose children had received vaccines in both countries. The participants were well acquainted with the NCIP, favored voluntary childhood vaccination, and the majority expressed a high level of trust in Norwegian health authorities.

Conclusions

Polish immigrants to Norway generally expressed positive views about childhood vaccination. Non-vaccination was related to lack of knowledge and/or unfamiliarity with certain vaccines and not with anti-vaccine sentiments or conspiracy theories. The study highlights how parents’ knowledge, in combination with norms and trends from both birth country and country of residence, influence parents’ decision making about vaccination.
Long-term effects of the COVID-19 lockdown on weight status, eating habits, and lifestyle changes related to school-aged children in Bandar Abbas, Iran
Authors: Khamesan Behnaz , Khatibzade-Nasari Niloufar , Zare Shahram , Rostami-Gooran Narges , Baghestani-Koozehgar Roya
Published: July 2024

Background

Despite the end of the COVID-19 lockdown and reopening of schools, the long-term effects of quarantine on the weight status, eating habits, and lifestyle of children and adolescents remain unknown. This study aimed to determine the long-term effects of the lockdown on the weight status, eating habits, and lifestyle changes of children and adolescents in Iran.

Method

This descriptive cross-sectional study was conducted from April to May 2022. The target population comprised one hundred students aged between 10 and 16 years old. Our study obtained students’ weight and height data from records maintained by school principals or physical education instructors before and after the quarantine period. The BMI z-score (zBMI) was calculated for each time point. The researchers also provided a questionnaire to collect the students’ demographic and lifestyle status changes during school closures.

Results

We found that the zBMI increased significantly from − 0.02 ± 1.64 to 0.36 ± 1.12, and the number of individuals with overweight and obesity increased by 3% during quarantine (P ≤ 0.05). These changes were more pronounced in males and students aged 14–16 years old. We also found that eating habits, sleeping time, sleeping patterns, screen time (time spent on social media per day), and physical activity had significant negative changes during quarantine, and a significant increase in zBMI was observed among students who experienced negative eating behaviors, altered sleeping patterns, and decreased physical activity during school closures.

Conclusion

As prolonged school closures due to the COVID-19 lockdown aggravated students’ health and lifestyle status, our findings can aid in proper planning to establish an appropriate framework for the diet, physical activity, and sleeping quality of students during extended school closures.
Cross-cultural adaptation and validation of the caregiver self-efficacy in contributing to patient self-care scale in China
Authors: Lv Qingyun , Zhang Xiaonan , Wang Yaqi , Xu Xueying , Zang Xiaoying
Published: July 2024

Background

Caregiver self-efficacy is crucial in improving patient outcomes and caregiver well-being, but there is a lack of suitable scales to assess this concept within the context of Chinese culture. This study aimed to cross-culturally translate the Caregiver Self-Efficacy in Contributing to Patient Self-Care (CSE-CSC) Scale and evaluate its psychometric properties using classical test theory and item response theory.

Methods

The CSE-CSC scale was adapted using Brislin’s translation model after obtaining authorization from the original author. A multicenter, cross-sectional study was conducted to assess the psychometric properties of this scale. Classical test theory was used to evaluate reliability (internal consistency, test-retest reliability), validity (content validity, structural validity, convergent validity), and floor and ceiling effects. Item response theory was employed to assess the fit of the rating scale model, reliability, item difficulties, and measurement invariance.

Results

The translation and cultural adaptation process was completed. Classical test theory demonstrated good internal consistency (Cronbach’s α = 0.935) and test-retest reliability (ICC from 0.784 to 0.829, p<0.001). The I-CVI and K* of each item ranged from 0.875 to 1.00 and 0.871 to 1.00. The first-order 2-factor model fit well (χ2/df = 3.71, RMSEA = 0.082, SRMR = 0.032, CFI = 0.973, TLI = 0.60). Convergent validity showed that the CSE-CSC scores had a strong positive correlation with three separate scales of the CC-SC-CII. There was no floor and ceiling effect in this scale. Rasch analysis showed that the CSE-CSC scale demonstrated a good fit to the rating scale model and exhibited excellent reliability (person/item separation index>2, person/item reliability coefficients>0.8). The Wright map showed that item difficulty matched the respondents’ measured abilities. The analysis of differential item functioning (DIF) showed that all items were comparable in gender.

Conclusions

This study indicated that the CSE-CSC scale had good reliability, validity, difficulty degree, and measurement invariance. The CSE-CSC scale can be used to measure caregiver self-efficacy of Chinese patients with multiple chronic conditions.
Predicting return of lung function after a pulmonary exacerbation using the cystic fibrosis respiratory symptom diary-chronic respiratory infection symptom scale
Authors: Gill Eliana R. , Goss Christopher H. , Sagel Scott D. , Wright Michelle L. , Horner Sharon D. , Zuñiga Julie A.
Published: July 2024

Background

Pulmonary exacerbations (PExs) in people with cystic fibrosis (PwCF) are associated with increased healthcare costs, decreased quality of life and the risk for permanent decline in lung function. Symptom burden, the continuous physiological and emotional symptoms on an individual related to their disease, may be a useful tool for monitoring PwCF during a PEx, and identifying individuals at high risk for permanent decline in lung function. The purpose of this study was to investigate if the degree of symptom burden severity, measured by the Cystic Fibrosis Respiratory Symptom Diary (CFRSD)- Chronic Respiratory Infection Symptom Scale (CRISS), at the onset of a PEx can predict failure to return to baseline lung function by the end of treatment.

Methods

A secondary analysis of a longitudinal, observational study (N = 56) was conducted. Data was collected at four time points: year-prior-to-enrollment annual appointment, termed “baseline”, day 1 of PEx diagnosis, termed “Visit 1”, day 10–21 of PEx diagnosis, termed “Visit 2” and two-weeks post-hospitalization, termed “Visit 3”. A linear regression model was performed to analyze the research question.

Results

A regression model predicted that recovery of lung function decreased by 0.2 points for every increase in CRISS points, indicating that participants with a CRISS score greater than 48.3 were at 14% greater risk of not recovering to baseline lung function by Visit 2, than people with lower scores.

Conclusion

Monitoring CRISS scores in PwCF is an efficient, reliable, non-invasive way to determine a person’s status at the beginning of a PEx. The results presented in this paper support the usefulness of studying symptoms in the context of PEx in PwCF.
Triglyceride-glucose index and combined indicators: effective indicators for screening NAFLD in snoring patients
Authors: Cai Yuqing , Chen Jia , Deng Xiaoyu , Wang Biying , Huang Jiefeng , Lian Ningfang
Published: July 2024

Aims

Nonalcoholic fatty liver disease (NAFLD) is a common complication in snoring patients, especially in patients with obstructive sleep apnea syndrome (OSA). Triglyceride-glucose (TyG) index was a simple indicator of metabolic status and a surrogate marker of insulin resistance. This study aimed to explore the relationship between NAFLD and TyG index in snoring patients.

Methods

A retrospective study was conducted. The successive snoring patients enrolled in the Sleep Center of the First Affiliated Hospital of Fujian Medical University and had abdominal ultrasonography were included. The clinical characteristics of patients in different quartile TyG groups were compared. The relationship of the TyG index and NAFLD were valued via logistic regression models and restricted cubic spline analysis. The value of TyG index in predicting NAFLD was determined by receiver operating characteristic curve (ROC curve).

Results

A total of 463 NAFLD cases were found among the 654 snoring patients. TyG index was a risk factor of NAFLD in snoring patients (OR = 2.38, 95% CI = 1.71–3.36). The risk of NAFLD was much higher in patients with the highest quartile of TyG index (OR = 5.12, 95% CI = 2.85–9.22), compared with the lowest quartile group. Restricted cubic spline (RCS) analysis showed a significant dose-response relationship between TyG index and risk of NAFLD (p for non-linearity < 0.001). A combination of TyG, neck circumference and ESS score presented the acceptable AUC for the detection of NAFLD in snoring patients (0.746, 95% CI 0.701–0.790, p < 0.001).

Conclusion

The TyG index was a risk factor of NAFLD in snoring patients. A combination of TyG, neck circumferences and ESS score could act as a convenient and effective indicator for screening NAFLD in snoring patients.
Controlling nutritional status score in the prediction of cardiovascular disease prevalence, all-cause and cardiovascular mortality in chronic obstructive pulmonary disease population: NHANES 1999–2018
Authors: Mai Suying , Nan Yayun , Peng Linlin , Wu Yuanbo , Chen Qiong
Published: July 2024

Background

Malnutrition is prevalent in chronic obstructive pulmonary disease (COPD) and associated with adverse outcomes, while COPD is intricately linked to cardiovascular disease (CVD), sharing common risk factors. The controlling nutritional status (CONUT) score, a promising tool for assessing malnutrition, warrants investigation into its predictive ability for cardiovascular disease prevalence and mortality in COPD patients.

Methods

Based on the National Health and Nutrition Examination Survey (NHANES), this study analyzed 1501 adult COPD patients from 1999 to 2018. The endpoints were CVD prevalence, mortality related to CVD, and overall mortality. We evaluated the correlation of the CONUT score with each outcome using logistic regression and Cox regression models. The prognostic evaluation of patients was conducted using Kaplan-Meier curves in accordance with the CONUT score. We formed the receiver operating characteristic (ROC) curves for evaluating the CONUT score's discriminative capability.

Results

The prevalence of malnutrition was 21.31% in COPD populations. Logistic analyses suggested a distinct connection between the CONUT score and CVD prevalence (OR:1.86, 95%CI:1.28-2.70) in individuals with COPD. The CONUT score demonstrated a significant correlation with a heightened risk of CVD mortality (HR: 1.86, 95%CI: 1.27-2.74) and overall mortality (HR: 1.50, 95%CI: 1.18-1.91). The prognostic outcomes might be effectively discriminated by the CONUT score, as seen by the Kaplan-Meier curves.

Conclusions

In summary, the CONUT score provides an uncomplicated and readily attainable marker for forecasting CVD prevalence, total mortality, and mortality from CVD among COPD patients.
Postoperative stroke in acute type A aortic dissection: incidence, outcomes, and perioperative risk factors
Authors: Raksamani Kasana , Tangvipattanapong Manisa , Charoenpithakwong Napat , Silarat Suparit , Pantisawat Natthaphorn , Sanphasitvong Vutthipong , Raykateeraroj Nattaya
Published: July 2024

Background

Despite advances in surgical techniques, the incidence of stroke following acute type A aortic dissection (ATAAD) repair remains markedly high, with substantial immediate and long-term adverse outcomes such as elevated mortality, extended hospital stays, and persistent neurological impairments. The complexity of managing ATAAD extends beyond the operation itself, highlighting a crucial gap in research concerning modifiable preoperative patient conditions and perioperative anesthetic management strategies.

Objectives

This investigation aimed to elucidate the incidence, consequences, and perioperative determinants of stroke following surgical intervention for acute type A aortic dissection (ATAAD).

Methods

In a multicenter retrospective analysis, 516 ATAAD surgery patients were evaluated. The data included demographic information, clinical profiles, surgical modalities, and outcomes. The primary endpoint was postoperative stroke incidence, with hospital mortality and other complications serving as secondary endpoints.

Results

Postoperative stroke occurred in 13.6% of patients (70 out of 516) and was associated with significant extension of the ICU (median 10 vs. 5 days, P < 0.001) and hospital stay (median 18 vs. 12 days, P < 0.001). The following key independent stroke risk factors were identified: modified Frailty Index (mFI) ≥ 4 (odds ratio [OR]: 4.18, 95% confidence interval [CI]: 1.24–14.1, P = 0.021), common carotid artery malperfusion (OR: 3.76, 95% CI: 1.23–11.44, P = 0.02), pre-cardiopulmonary bypass (CPB) hypotension (mean arterial pressure ≤ 50 mmHg; OR: 2.17, 95% CI: 1.06–4.44, P = 0.035), ≥ 20% intraoperative decrease in cerebral regional oxygen saturation (rSO2) (OR: 1.93, 95% CI: 1.02–3.64, P = 0.042), and post-CPB vasoactive-inotropic score (VIS) ≥ 10 (OR: 2.24, 95% CI: 1.21–4.14, P = 0.01).

Conclusions

Postoperative stroke significantly increases ICU and hospital durations in ATAAD surgery patients. These findings highlight the critical need to identify and mitigate major risks, such as high mFI, common carotid artery malperfusion, pre-CPB hypotension, significant cerebral rSO2 reductions, and elevated post-CPB VIS, to improve outcomes and reduce stroke prevalence.

Trial Registration

Thai Clinical Trials Registry (TCTR20230615002). Date registered on June 15, 2023. Retrospectively registered.
Protective effects of the R-(+)-thioctic acid treatment: possible anti-inflammatory activity on heart of hypertensive rats
Authors: Roy Proshanta , Tomassoni Daniele , Martinelli Ilenia , Bellitto Vincenzo , Nittari Giulio , Amenta Francesco , Tayebati Seyed Khosrow
Published: July 2024

Background

In cardiovascular disease, high blood pressure is associated with oxidative stress, promoting endothelial dysfunction, vascular remodeling, and inflammation. Clinical trials are discordant that the most effective treatment in the management of hypertension seems to be the administration of anti-hypertensive drugs with antioxidant properties. The study aims to evaluate the effects of the eutomer of thioctic acid on oxidative stress and inflammation in the heart of spontaneously hypertensive rats compared to normotensive Wistar Kyoto rats.

Methods

To study the oxidative status, the malondialdehyde and 4-hydroxynonenal concentration, protein oxidation were measured in the heart. Morphological analysis were performed. Immunohistochemistry and Western blot were done for alpha-smooth muscle actin and transforming growth factor beta to assess fibrosis; cytokines and nuclear factor kappaB to assess inflammatory processes.

Results

Spontaneously hypertensive rats were characterized by hypertension with increased malondialdehyde levels in the heart. OxyBlot in the heart of spontaneously hypertensive rats showed an increase in proteins’ oxidative status. Cardiomyocyte hypertrophy and fibrosis in the ventricles were associated with an increased expression of alpha-smooth muscle actin and pro-inflammatory cytokines, reduced by the eutomer of thioctic acid supplementation.

Conclusions

Based on this evidence, eutomer of thioctic acid could represent an appropriate antioxidant molecule to reduce oxidative stress and prevent inflammatory processes on the cardiomyocytes and cardiac vascular endothelium.
Factors associated with medical students’ career choice in different specialties: a multiple cross-sectional questionnaire study at a German medical school
Authors: Leutritz Tobias , Krauthausen Maike , Simmenroth Anne , König Sarah
Published: July 2024

Background

Given the shortage and unequal distribution of physicians across specialties, we aimed to evaluate factors associated with medical students’ career choices, including background, personality traits, educational experience, personal interests, lifestyle considerations, and the awareness of work requirements.

Methods

We conducted multiple cross-sectional surveys of students; a 159-item online questionnaire was designed and students from three different stages of the six-year medical degree course (outset, clinical phase, and on graduation) were invited to complete the survey. Data were collected between May 2021 and April 2023.

Results

The questionnaire was sent to 1406 students, of whom 683 replied (49%); 481 respondents were female (70%). The top specialty choices across the respondents were internal medicine, surgery, and general practice, with anaesthesiology, paediatric and adolescent medicine (ranging 11–15%), and obstetrics and gynaecology also receiving interest, with 6% undecided. In particular, female students lost interest in surgery during the course of study in favour of the other options. The choice of general practice was associated with more vocational training, prior positive experiences with the specialty, and lower grades in the university entry examination. Clinical clerkships in a specific (freely chosen) specialty aligned with career choice, while the final practical year did not have an impact on career decision-making. All students highly desired regulated working hours and work-life-balance; however, students choosing surgery rated these items as less important. Willingness to work in a hospital environment was highly associated with choosing anaesthesiology and surgery, whereas rural areas and practices were associated with general practice. Higher scores at agreeableness were associated with choosing paediatric and adolescent medicine by more female students, whereas lower neuroticism values were associated with the choice of anaesthesiology.

Conclusions

The results highlight the intricate nature of decision-making and shed light on various aspects that contribute to the process of selecting a specialty. By identifying and addressing influencing factors, we can develop targeted interventions and policies to enhance diversity and distribution across medical specialisations and to aim for high-quality and equitable healthcare that matches the specific needs of both individuals and the population as a whole.

Graphical Abstract
Building stronger foundations: exploring a collaborative faculty mentoring workshop for in-depth growth
Authors: Rehman Rehana , Arooj Mahwish , Ali Rahila , Ali Tazeen Saeed , Javed Kainat , Chaudhry Saima
Published: July 2024

Background

Mentorship training programs demand a paradigm shift from theory-driven to hands-on practical approach with prioritization of preparation of mentors and mentees for their roles through self-awareness and targeted professional development planning. There is a lack of evidence generated from the health professions education institutions of global south regarding effectiveness of workshops in fostering mentorship culture.

Methods

This mixed method study with convergent parallel design was conducted through a collaborative mentoring workshop; “Faculty Mentoring-Building stronger by digging deeper” by Aga khan University Medical College, Karachi and University of Lahore, Punjab, Pakistan. Objective of the research was to emphasize the importance of faculty mentoring program, roles and responsibilities of mentors and mentees and perception of the participants regarding the associated role of institutions. It aimed to educate faculty members to develop personal development plans for becoming effective mentors and mentees. The demographic data was collected before the workshop, during the workshop data was collected from SWOT analysis, followed by goal settings and the action plans made by participants at the end. Post workshop online feedback was acquired by a questionnaire to comprehend participants’ educational attainment. Association between quantitative findings was done through ANOVA, while the qualitative data was subjected to thematic analysis.

Results

Total of 37 faculty members participated in the hands-on workshop. All faculty equally perceived the workshop as satisfactory and reported that hands-on practice led to positive experience of setting clear goals and action plans in developing oneself both as mentor and mentee. Themes identified were; Faculty Mentorship Program, Personal development Plan of Mentors and Mentees and Building Positive Mentor-Mentee Relationships. Voluntary structured program, choice of more than one faculty mentor and portfolio development based on personal SWOT was recommended by participants for the success of formal mentoring programs.

Conclusion

Medical Faculty of Pakistani Universities at all career levels is interested in development of formal mentoring programs in their universities. Formal training for the same is also recommended by the participants. Institutions should cultivate a culture of mentorship that supports the professional growth and success of academics for cultivating the minds that are in turn shaping our future generations.
The body as an obstacle and the “other”. How patients with chronic inflammatory bowel diseases view their body, self and the good life
Authors: Erdmann Anke , Rehmann-Sutter Christoph , Schrinner Florian , Bozzaro Claudia
Published: July 2024

Background

Treatment of chronic inflammatory bowel disease (IBD) aims to improve patients’ quality of life and the extent of treatment success is measured via patient reported outcomes (PROs). However, questionnaires used to collect PROs often include scales that are not specific to IBDs. Improving these scales requires a deeper understanding of patients’ lived experience. With this study we give first insights and develop hypotheses on how patients with IBDs experience their body and self and how they adjust their life plans in the context of precision medicine (PM). The guiding question is to understand what they need to achieve a good life, while facing their disease.

Methods

We developed a conception of the “good life” that draws on Philippa Foot’s “naturalized” approach and distinguishes six different dimensions that are relevant for a good life. This conception guided us as we conducted 10 qualitative interviews with patients suffering from IBD who were in precision medicine clinical research settings. The interviews aimed to gain insights for answering our research question: How do body experiences affect the good life of patients with IBD? We analyzed the interviews with interpretative phenomenological analysis (IPA).

Results

Five group experiential themes emerged: (i) Life options and plans, (ii) other people’s responses, (iii) strategies to deal with others’ responses, (iv) perception of the body and self, and (v) perception of life as good despite suffering. We report here on three of them (i, iv and v), which are primarily relevant for evaluating the outcomes of PM care. Whereas with “life options and plans (i),” our study predominantly confirmed previous research, with “perception of the body and self (iv),” we found that some of the patients changed their relationship to their body and themselves. They perceived the body or the disease as the “other” and their self appears divorced from their own body. Although this might be an avoidance strategy patients use to assign responsibility for their condition and its “disgusting” symptoms to the “other,” it is important to include it in patient reported outcome (PRO) assessments.

Conclusions

We conclude with the insight that the multi-dimensional approach based on Foot’s concept of a good life is well-suited as a basis for investigating the quality of life of people with IBD. Interviews based on this concept produced results that go beyond the understanding of health-related quality of life (HRQoL). Additionally, we offer some considerations about patients’ opportunities for achieving a good life and suggestions for further developing patient reported outcome scales.
Incorporating informatively collected laboratory data from EHR in clinical prediction models
Authors: Sun Minghui , Engelhard Matthew M. , Bedoya Armando D. , Goldstein Benjamin A.
Published: July 2024

Background

Electronic Health Records (EHR) are widely used to develop clinical prediction models (CPMs). However, one of the challenges is that there is often a degree of informative missing data. For example, laboratory measures are typically taken when a clinician is concerned that there is a need. When data are the so-called Not Missing at Random (NMAR), analytic strategies based on other missingness mechanisms are inappropriate. In this work, we seek to compare the impact of different strategies for handling missing data on CPMs performance.

Methods

We considered a predictive model for rapid inpatient deterioration as an exemplar implementation. This model incorporated twelve laboratory measures with varying levels of missingness. Five labs had missingness rate levels around 50%, and the other seven had missingness levels around 90%. We included them based on the belief that their missingness status can be highly informational for the prediction. In our study, we explicitly compared the various missing data strategies: mean imputation, normal-value imputation, conditional imputation, categorical encoding, and missingness embeddings. Some of these were also combined with the last observation carried forward (LOCF). We implemented logistic LASSO regression, multilayer perceptron (MLP), and long short-term memory (LSTM) models as the downstream classifiers. We compared the AUROC of testing data and used bootstrapping to construct 95% confidence intervals.

Results

We had 105,198 inpatient encounters, with 4.7% having experienced the deterioration outcome of interest. LSTM models generally outperformed other cross-sectional models, where embedding approaches and categorical encoding yielded the best results. For the cross-sectional models, normal-value imputation with LOCF generated the best results.

Conclusion

Strategies that accounted for the possibility of NMAR missing data yielded better model performance than those did not. The embedding method had an advantage as it did not require prior clinical knowledge. Using LOCF could enhance the performance of cross-sectional models but have countereffects in LSTM models.
A self-assessment maturity matrix to support large-scale change using collaborative networks in the New Zealand health system
Authors: Sharma Kanchan M. , Jones Peter B. , Cumming Jacqueline , Middleton Lesley
Published: July 2024

Background

A maturity matrix can be a useful tool for organisations implementing large-system transformation (LST) initiatives in complex systems. Insights from implementation of a local LST initiative using collaborative networks, known as Alliances, highlighted a tool was needed to help health system leaders prompt discussions on how and where to focus their change efforts. In the New Zealand (NZ) health system, Alliances were introduced to integrate the planning and delivery of health care between primary and hospital care.

Methods

The aim of this research was to use insights from Alliance members to develop a learning tool that collaborative networks could use to assess and improve their readiness for change. We constructed a maturity matrix using the knowledge of senior NZ health system leaders, in a workshop setting. The maturity matrix was empirically tested and refined with three Alliances and with feedback from the NZ Ministry of Health Māori Health Strategy and Policy team.

Results

The maturity matrix described the 10 key elements that had been found to support successful implementation of LST initiatives in the NZ health system, along with success indicators and different stages of maturity from beginning to excellence. Testing of the maturity matrix with three Alliances suggested that it functioned as a learning tool and stimulated collective thinking and reflection. The Māori Health Strategy and Policy team commented on the importance of such a tool to increase health system leaders’ responsiveness to improving Māori health outcomes. Comparisons with similar international matrices revealed common elements with ours. A strength of our maturity matrix is that it is specific to the NZ context and is the first practical tool to implement large-scale change in the health system that incorporates principles of the Government’s treaty with Māori, the indigenous people of NZ.

Conclusions

Through a regular self-assessment process, use of the maturity matrix may create feedback loops to support deliberate learning and knowledge sharing for senior health system leaders and collaborative networks. The maturity matrix fills an important gap in the NZ health system and contributes to implementation science literature internationally.

Other

This study was approved by the Victoria University of Wellington Human Ethics Committee (Ethics Approval Number 27,356). The research was supported by the Victoria University of Wellington research grant (222,809) and from the University of Auckland Department of Medicine research fund (H10779).
Identifying cost-based quality and performance indicators for home care: a modified delphi method study
Authors: Jajszczok Max , Eastwood Cathy A. , Lu Mingshan , Cunningham Ceara , Southern Danielle A. , Quan Hude
Published: July 2024

Background

This study, part of a multi-study program, aimed to identify a core set of cost-based quality and performance indicators using a modified Delphi research approach. Conceptually, this core set of cost-based indicators is intended for use within a broader health system performance framework for evaluating home care programming in Canada.

Methods

This study used findings from a recently published scoping review identifying 34 cost-focused home care program PQIs. A purposive and snowball technique was employed to recruit a national panel of system-level operational and content experts in home care. We collected data through progressive surveys and engagement sessions. In the first round of surveying, the panel scored each indicator on Importance, Actionable, and Interpretable criteria. The panel set the second round of ranking the remaining indicators’ consensus criteria. The panel ranked by importance their top five indicators from operational and system perspectives. Indicators selected by over 50% of the panel were accepted as consensus.

Results

We identified 13 panellists. 12 completed the first round which identified that 30 met the predetermined inclusion criteria. Eight completed the ranking exercise, with one of the eight completing one of two components. The second round resulted in three PQIs meeting the consensus criteria: one operational and two systems-policy-focused. The PQIs: “Average cost per day per home care client,” “Home care service cost (mean) per home care client 1y, 3y and 7y per health authority and provincially and nationally”, and “Home care funding as a percent of overall health care expenditures.”

Conclusions

The findings from this study offer a crucial foundation for assessing operational and health system outcomes. Notably, this research pioneers identifying key cost-based PQIs through a national expert panel and modified Delphi methodology. This study contributes to the literature on PQIs for home care and provides a basis for future research and practice. These selected PQIs should be applied to future research to test their applicability and validity within home care programming and outcomes. Researchers should apply these selected PQIs in future studies to evaluate their applicability and validity within home care programming and outcomes.
Strategies used to detect and mitigate system-related errors over time: A qualitative study in an Australian health district
Authors: Kinlay Madaline , Zheng Wu Yi , Burke Rosemary , Juraskova Ilona , Ho Lai Mun , Turton Hannah , Trinh Jason , Baysari Melissa T.
Published: July 2024

Background

Electronic medical record (EMR) systems provide timely access to clinical information and have been shown to improve medication safety. However, EMRs can also create opportunities for error, including system-related errors or errors that were unlikely or not possible with the use of paper medication charts. This study aimed to determine the detection and mitigation strategies adopted by a health district in Australia to target system-related errors and to explore stakeholder views on strategies needed to curb future system-related errors from emerging.

Methods

A qualitative descriptive study design was used comprising semi-structured interviews. Data were collected from three hospitals within a health district in Sydney, Australia, between September 2020 and May 2021. Interviews were conducted with EMR users and other key stakeholders (e.g. clinical informatics team members). Participants were asked to reflect on how system-related errors changed over time, and to describe approaches taken by their organisation to detect and mitigate these errors. Thematic analysis was conducted iteratively using a general inductive approach, where codes were assigned as themes emerged from the data.

Results

Interviews were conducted with 25 stakeholders. Participants reported that most system-related errors were detected by front-line clinicians. Following error detection, clinicians either reported system-related errors directly to the clinical informatics team or submitted reports to the incident information management system. System-related errors were also reported to be detected via reports run within the EMR, or during organisational processes such as incident investigations or system enhancement projects. EMR redesign was the main approach described by participants for mitigating system-related errors, however other strategies, like regular user education and minimising the use of hybrid systems, were also reported.

Conclusions

Initial detection of system-related errors relies heavily on front-line clinicians, however other organisational strategies that are proactive and layered can improve the systemic detection, investigation, and management of errors. Together with EMR design changes, complementary error mitigation strategies, including targeted staff education, can support safe EMR use and development.
Development of novel antimicrobials with engineered endolysin LysECD7-SMAP to combat Gram-negative bacterial infections
Authors: Vasina Daria V. , Antonova Nataliia P. , Gushchin Vladimir A. , Aleshkin Andrey V. , Fursov Mikhail V. , Fursova Anastasiia D. , Gancheva Petya G. , Grigoriev Igor V. , Grinkevich Pavel , Kondratev Alexey V. , Kostarnoy Alexey V. , Lendel Anastasiya M. , Makarov Valentine V. , Nikiforova Maria A. , Pochtovyi Andrei A. , Prudnikova Tatiana , Remizov Timofey A. , Shevlyagina Natalia V. , Siniavin Andrei E. , Smirnova Nina S. , Terechov Alexander A. , Tkachuk Artem P. , Usachev Evgeny V. , Vorobev Aleksei M. , Yakimakha Victoria S. , Yudin Sergey M. , Zackharova Anastasia A. , Zhukhovitsky Vladimir G. , Logunov Denis Y. , Gintsburg Alexander L.
Published: July 2024

Background

Among the non-traditional antibacterial agents in development, only a few targets critical Gram-negative bacteria such as carbapenem-resistant Pseudomonas aeruginosa, Acinetobacter baumannii or cephalosporin-resistant Enterobacteriaceae. Endolysins and their genetically modified versions meet the World Health Organization criteria for innovation, have a novel mode of antibacterial action, no known bacterial cross-resistance, and are being intensively studied for application against Gram-negative pathogens.

Methods

The study presents a multidisciplinary approach, including genetic engineering of LysECD7-SMAP and production of recombinant endolysin, its analysis by crystal structure solution following molecular dynamics simulations and evaluation of antibacterial properties. Two types of antimicrobial dosage forms were formulated, resulting in lyophilized powder for injection and hydroxyethylcellulose gel for topical administration. Their efficacy was estimated in the treatment of sepsis, and pneumonia models in BALB/c mice, diabetes-associated wound infection in the leptin receptor-deficient db/db mice and infected burn wounds in rats.

Results

In this work, we investigate the application strategies of the engineered endolysin LysECD7-SMAP and its dosage forms evaluated in preclinical studies. The catalytic domain of the enzyme shares the conserved structure of endopeptidases containing a putative antimicrobial peptide at the C-terminus of polypeptide chain. The activity of endolysins has been demonstrated against a range of pathogens, such as Klebsiella pneumoniae, A. baumannii, P. aeruginosa, Staphylococcus haemolyticus, Achromobacter spp, Burkholderia cepacia complex and Haemophylus influenzae, including those with multidrug resistance. The efficacy of candidate dosage forms has been confirmed in in vivo studies. Some aspects of the interaction of LysECD7-SMAP with cell wall molecular targets are also discussed.

Conclusions

Our studies demonstrate the potential of LysECD7-SMAP therapeutics for the systemic or topical treatment of infectious diseases caused by susceptible Gram-negative bacterial species and are critical to proceed LysECD7-SMAP-based antimicrobials trials to advanced stages.
Effect of extracellular matrix stiffness on efficacy of Dapagliflozin for diabetic cardiomyopathy
Authors: Zhu Tong , Ye Zhaoyang , Song Jingjing , Zhang Junjie , Zhao Yuxiang , Xu Feng , Wang Jun , Huang Xin , Gao Bin , Li Fei
Published: July 2024

Background

Extracellular matrix (ECM) stiffness is closely related to the progress of diabetic cardiomyopathy (DCM) and the response of treatment of DCM to anti-diabetic drugs. Dapagliflozin (Dapa) has been proven to have cardio-protective efficacy for diabetes and listed as the first-line drug to treat heart failure. But the regulatory relationship between ECM stiffness and treatment efficacy of Dapa remains elusive.

Materials and methods

This work investigated the effect of ECM stiffness on DCM progression and Dapa efficacy using both in vivo DCM rat model and in vitro myocardial cell model with high glucose injury. First, through DCM rat models with various levels of myocardial injury and administration with Dapa treatment for four weeks, the levels of myocardial injury, myocardial oxidative stress, expressions of AT1R (a mechanical signal protein) and the stiffness of myocardial tissues were obtained. Then for mimicking the stiffness of myocardial tissues at early and late stages of DCM, we constructed cell models through culturing H9c2 myocardial cells on the polyacrylamide gels with two stiffness and exposed to a high glucose level and without/with Dapa intervention. The cell viability, reactive oxygen species (ROS) levels and expressions of mechanical signal sensitive proteins were obtained.

Results

The DCM progression is accompanied by the increased myocardial tissue stiffness, which can synergistically exacerbate myocardial cell injury with high glucose. Dapa can improve the ECM stiffness-induced DCM progression and its efficacy on DCM is more pronounced on the soft ECM, which is related to the regulation pathway of AT1R-FAK-NOX2. Besides, Dapa can inhibit the expression of the ECM-induced integrin β1, but without significant impact on piezo 1.

Conclusions

Our study found the regulation and effect of biomechanics in the DCM progression and on the Dapa efficacy on DCM, providing the new insights for the DCM treatment. Additionally, our work showed the better clinical prognosis of DCM under early Dapa intervention.
Differentiated management of ROS level in tumor and kidney to alleviate Cis-platinum induced acute kidney injury with improved efficacy
Authors: Zhu Shiqi , Huo Linlin , Zeng Jie , Chen Rong , Sun Yutong , Tan Mingya , Fan Mengke , Liu Meiling , Zhao Jiayi , Huang Guoming , Wang Yi , Xiao Zhibo , Zhao Zhenghuan
Published: July 2024

Cisplatin (DDP) is a prevalent chemotherapeutic agent used in tumor therapy, yet DDP-induced acute kidney injury (AKI) severely limits its clinical application. Antioxidants as reactive oxygen species (ROS) scavengers can circumvent this adverse effect while leading to the decrease of efficacy to tumor. Herein, we report ultrasmall ruthenium nanoparticles (URNPs) as switchable ROS scavengers/generators to alleviate DDP-induced AKI and improve its therapeutic efficacy. In the physiological environment of the kidney, URNPs mimic multi-enzyme activities, such as superoxide dismutase and catalase, effectively protecting the renal cell and tissue by down-regulating the increased ROS level caused by DDP and alleviating AKI. Specifically, URNPs are oxidized by high levels of H2O2 in the tumor microenvironment (TME), resulting in the generation of oxygen vacancies and Ru3+/Ru4+ ions. This unique structure transformation endows URNPs to generate singlet oxygen (1O2) under laser irradiation and hydroxyl radicals (∙OH) through a Fenton-like reaction in tumor cell and tissue. The simultaneous generation of multifarious ROS effectively improves the efficacy of DDP in vitro and in vivo. This TME-responsive ROS scavenger/generator acts as an adjuvant therapeutic agent to minimize side effects and improve the efficacy of chemotherapy drugs, providing a new avenue to chemotherapy and facilitating clinical tumor therapy.

Graphical Abstract
Radiofrequency ablation versus laparoscopic hepatectomy for hepatocellular carcinoma: a systematic review and meta-analysis
Authors: Jiang Chuang , Feng Qingbo , Zhang Zhihong , Qiang Zeyuan , Du Ao , Xu Lin , Li Jiaxin
Published: July 2024

Background

Although laparoscopic hepatectomy (LH) and radiofrequency ablation (RFA) are the 2 principal minimally invasive surgical approaches and the first line of treatments for patients with hepatocellular carcinoma (HCC). It is not clear which one has greater safety and efficacy. In this meta-analysis, we aim to compare the safety and effectiveness of LH versus RFA for patients with HCC, especially where perioperative and postoperative outcomes differrent.

Methods

In PROSPERO, a meta-analysis with registration number CRD42021257575 was registered. Using an established search strategy, we systematically searched Web of Science, PubMed, and Embase to identify eligible studies before June 2023. Data on operative times, blood loss, length of stay, overall complications, overall survival (OS) and recurrence-free survival (RFS) were subjected to meta-analysis.

Results

Overall, the present meta-analysis included 8 retrospective and 6 PSM studies comprising 1,848 patients (810 and 1,038 patients underwent LH and RFA). In this meta-analysis, neither LH nor RFA showed significant differences in 1-year and 3-year OS rate and 5-year RFS rate. Despite this, in comparison to the RFA group, LH resulted in significantly higher 1-year(p<0.0001) and 3-year RFS rate (p = 0.005), higher 5-year OS rate (p = 0.008), lower local recurrence rate (p<0.00001), longer length of stay(LOS) (p<0.0001), longer operative time(p<0.0001), more blood loss (p<0.0001), and higher rate of complications (p=0.001).

Conclusions

Comparative studies indicate that LH seemed to provide better OS and lower local recurrence rate, but higher complication rate and longer hospitalization.