bluuebunny/crossref_metadata_2025 huggingface dataset:
Flipping the classroom in neurological bedside teaching: a prospective controlled study
Authors: Heitmann Henrik , Fischer Elisabeth , Wagner Philipp , Pötter Dennis , Gartmeier Martin , Schmidt-Graf Friederike
Published: March 2023

Background

Bedside teaching is essential to foster core clinical competences in medical education, especially in Neurology. However, bedside skills are declining and new concepts to enhance the effectiveness of bedside teaching are needed, also in view of limited in-person teaching possibilities in the ongoing pandemic situation. If theoretical knowledge is taught prior to in-person sessions this might allow to better focus on practical application aspects during bedside teaching. We thus aimed to answer the question to what extent such an approach can enhance the effectiveness of neurological bedside teaching.

Methods

In this prospective controlled study, neurological bedside courses following a traditional and a flipped classroom (FC) approach were compared with regards to their effects on theoretical knowledge and practical skills of medical students. Evaluations were obtained from 161 students and their lecturers participating in a neurological bedside teaching course at a German university hospital between October 2020 and July 2021. Students were randomly assigned to course dates. However, the 74 students assigned to course dates from May to July 2021 completed a mandatory online preparation course prior to the bedside teaching. These students served as the interventional group (IG) and the remaining 87 students formed the control group (CG). Ratings of knowledge and skills provided by the students and their lecturers on numerical rating scales served as primary outcome measures. Moreover, the time needed to recapitulate theoretical contents during the in-person teaching session was assessed as a secondary outcome measure. Group comparisons were performed using t-statistics.

Results

Theoretical knowledge upon entering the course was rated significantly higher in the IG by the students (p < 0.001) and lecturers (p = 0.003). Lecturers also rated the practical skills of students in the IG significantly higher (p < 0.001). Furthermore, significantly less time was needed to recapitulate theoretical contents during the in-person session in the IG (p = 0.03).

Conclusions

Using a FC approach enhances the effectiveness of in-person neurological bedside teaching. Thus, these concepts are particularly valuable in the ongoing pandemic situation. Moreover, they might allow to reuse e-learning contents developed during the pandemic and to develop future bedside teaching concepts.
The current status of “spirituality and health” teaching in Brazilian medical schools: a nationwide survey
Authors: Lucchetti Giancarlo , de Araujo Almeida Paulo Othavio , Martin Elena Zuliani , Góes Leonardo Garcia , Cotta Keylla Cássia Gomes , Lima Andressa Correia , da Silva Ezequiel Oscarina , Lucchetti Alessandra Lamas Granero
Published: March 2023

Background

Recent data on the teaching of “spirituality and health” (S/H) in medical schools are needed. In this study, we aimed to investigate the current status of S/H teaching in Brazilian medical schools, the opinions of medical directors/deans on this topic and the factors associated with its incorporation into the curriculum.

Methods

A nationwide cross-sectional survey was carried out in 2021. Information concerning the S/H content in the curricula of medical schools was obtained through medical school representatives and other sources. Medical school representatives were asked about their opinions of and barriers to S/H teaching. Regression models were used to evaluate the factors associated with the incorporation of such content into the curriculum.

Results

Information on the incorporation of S/H content in medical curricula was retrieved from different sources for all 342 (100%) Brazilian medical schools. Among the representatives, 150 (43.9%) completed the online form. An increase in the S/H content in Brazilian medical schools was observed (from 40% to 2011 to 65.5% in 2021). Most medical school representatives agreed that this issue is important in medical training and that more space in the curriculum is needed. However, they also observed several barriers, such as a lack of knowledge of medical teachers/faculty, a lack of time, and the topic not being included in teaching plans. The most important factors that influenced the incorporation of S/H teaching in medical schools and representatives’ opinions were a lack of time and knowledge, professor preparedness and standardized national competency requirements.

Conclusion

These results could help medical educators rethink the incorporation of S/H content into their curricula.
Knowledge, attitudes and practices of university students toward COVID-19 in Southern region, Afghanistan: a cross-sectional study
Authors: Sirat Rahmatullah , Sahrai Mohammad Sediq , Rahimi Bilal Ahmad , Asady Abdullah , Wasiq Abdul Wahed
Published: March 2023

Background

Successful implementation of preventive measures and level of awareness in particular among university students in Afghanistan could play a crucial role in spreading the information for better control of the ongoing pandemic. Therefore, the aim of this study was to determine the level of knowledge, attitudes and practices (KAP) regarding COVID-19 among Kandahar university students.

Methods

A cross-sectional study conducted among undergraduate students to investigate their KAP regarding COVID-19 from January to March, 2021. The data were collected using a structured questionnaire (socio-demographic characteristics, KAP questionnaire) by phone call interviews.

Results

From 359 participants, 88.9% were males, 81.3% were single, 65.1% lived in urban areas, and more than 64% of the students were less than 23 years old. Overall, 86.6% of the study participants had adequate level of knowledge and 87.5% had positive attitudes toward COVID-19. Almost one-third of the participants had good practices regarding COVID-19. All KAP scores were higher in male students. Significant difference of good practice (p < 0.001) was observed among students who were in high socioeconomic status (SES) group. In univariate analysis, female sex (β: -0.75, p = 0.007) was negatively and watching television (β: 0.44; p = 0.014) was positively associated with knowledge score. However, in multivariate linear regression analysis, the knowledge score was significantly associated with age (β: -0.115; p = 0.004); attitude score was significantly associated with female sex (β: -2.776; p < 0.001) and radio use (β: -0.974; p = 0.031); and practice score was significantly associated with female sex (β: -3.704; p = 0.002) and urban area (β: 1.702; p = 0.016).

Conclusions

The overall knowledge and attitudes regarding COVID-19 among university students were desirable. Higher university year, young age, male sex and living in urban areas were significantly associated with good KAP regarding COVID-19. Good practices towards COVID-19 should be increased through awareness programs.
Active legs: Impact of physical activity as an adjuvant treatment in the healing of venous ulcers in primary care: a RCT protocol study
Authors: Herraiz-Ahijado Borja , Folguera-Álvarez Carmen , Verdú-Soriano José , Mori-Vara Pilar , Rico-Blázquez Milagros
Published: March 2023

Background

Venous ulcers usually present a torpid evolution with a negative impact on patients’ quality of life. In primary care, they account for 2.5% of nursing consultations and their treatment represents high costs for national health systems. These patients usually have a low level of physical activity, with muscle pump dysfunction of the lower limbs, which may improve with increased physical activity. The purpose of this study is to analyse the effectiveness of a structured intervention involving physical activity and exercise (Active Legs) as an adjuvant treatment in improving healing of chronic venous ulcers at 3 months follow-up.

Methods

A randomized, multicentre clinical trial. A total of 224 individuals receiving primary nursing care with a diagnosis of venous ulcer, with a diameter of 1 cm or greater and an ankle-brachial index between 0.8 and 1.3, able to comply with the study requirements and consenting to participate, will be sequentially included (112 per group).

Both groups will receive the standard treatment in primary care, with cleansing, debridement and healing in a moist environment together with multilayer compression therapy. The intervention group will also receive a structured educational intervention involving lower limb physical exercise and daily ambulation guidelines.

The primary response variables will be complete healing –understood as complete and sustained epithelialisation for at least 2 weeks– and time to healing. The secondary variables will be degree of healing, ulcer area, quality of life, pain and variables related to the healing process, prognosis, and recurrences. Sociodemographic variables, adherence to treatment and satisfaction variables will also be recorded. Data will be collected at baseline, at 3 months and at 6 months follow-up. Survival analysis (Kaplan-Meier and Cox) will be performed to measure primary effectiveness. Intention-to-treat analysis.

Discussion

If the intervention is effective, a cost-effectiveness analysis could be conducted and implemented as an additional intervention in the usual venous ulcer treatment in primary care.

Trial registration

NCT04039789. [https://ClinicalTrials.gov]. 07/11/2019.
Assistive robotic systems in nursing care: a scoping review
Authors: Ohneberg Christoph , Stöbich Nicole , Warmbein Angelika , Rathgeber Ivanka , Mehler-Klamt Amrei Christin , Fischer Uli , Eberl Inge
Published: March 2023

Background

The use of assistive robotic systems in care is intended to relieve nursing staff. Differentiated and literature-based findings on current application possibilities, technological developments and empirical findings are necessary to enable a goal-oriented and participatory development of assistive robotic systems of care. The aim of this review was to identify assistive robotic systems and their areas of application in nursing settings. Furthermore, an overview of existing social and nursing science findings from the research field of assistive robotic systems will be described.

Methods

A systematic literature search was performed based on the JBI scoping review methodology. During the period from May to August 2020, the databases MEDLINE via PubMed, CINAHL, Cochrane Library, Web of Science, and IEEE Xplore Digital Library were searched. In order to reflect current developments and evidence in the present literature work, a supplementary search with these same requirements was conducted in January 2022.

Results

The 47 included publications are divided into 15 studies, 23 technical articles and nine opinion-based articles (text-opinion). A total of 39 different assistive robotic systems were identified. There were 55% in the testing phase and 29% of the systems in the development phase. Assistive robotic systems can be divided into six fields of application: Information and patient data processing, assistance with activities of daily living, fetch and bring activities, telepresence and communication, monitoring, safety and navigation, and complex assistance systems. The description of the study findings is divided into "integration of technology and impact on practice" and "attitude and acceptance of elderly people towards assistive robotic systems".

Conclusion

The results of the research show that the use of assistive robotic systems in care mainly take place in the context of development and testing phases. In addition to usability and acceptance issues, implementation factors must be integrated into theory-driven research projects.
Effectiveness of a critical reflection competency program for clinical nurse educators: a pilot study
Authors: Shin Sujin , Lee Inyoung , Kim Jeonghyun , Oh Eunyoung , Hong Eunmin
Published: March 2023

Background

Critical reflection is an effective learning strategy that enhances clinical nurses’ reflective practice and professionalism. Therefore, training programs for nurse educators should be implemented so that critical reflection can be applied to nursing education. This study aimed to investigate the effects of a critical reflection competency program for clinical nurse educators on improving critical thinking disposition, nursing reflection competency, and teaching efficacy.

Methods

A pilot study was conducted using a pre- and post-test control-group design. Participants were clinical nurse educators recruited using a convenience sampling method. The program was conducted once a week for 90 min, with a total of four sessions. The effectiveness of the developed program was verified by analyzing pre- and post-test results of 26 participants in the intervention group and 27 participants in the control group, respectively. The chi-square test, independent t-test, Mann-Whitney U test, and analysis of covariance with age as a covariate were conducted.

Results

The critical thinking disposition and teaching efficacy of the intervention group improved after the program, and the differences between the control and intervention groups were statistically significant (F = 14.751, p < 0.001; F = 11.047, p < 0.001). There was no significant difference in the change in nursing reflection competency between the two groups (F = 2.674, p = 0.108).

Conclusion

The critical reflection competency program was effective in improving the critical thinking disposition and teaching efficacy of nurse educators. Therefore, it is necessary to implement the developed program for nurse educators to effectively utilize critical reflection in nursing education.
Cost and outcomes of routine HIV care and treatment: public and private service delivery models covering low-income earners in South Africa
Authors: Long L. C. , Girdwood S. , Govender K. , Meyer-Rath G. , Miot J.
Published: March 2023

Background

While South Africa’s national HIV program is the largest in the world, it has yet to reach the UNAIDS 95–95-95 targets. To reach these targets, the expansion of the HIV treatment program may be accelerated through the use private sector delivery models. This study identified three innovative non-governmental primary health care models (private sector) providing HIV treatment, as well as two government primary health clinics (public sector) that served similar populations. We estimated the resources used, and costs and outcomes of HIV treatment across these models to provide inputs to inform decisions around how these services might best be provided through National Health Insurance (NHI).

Methods

A review of potential private sector models for HIV treatment in a primary health care setting was conducted. Models actively offering HIV treatment (i.e. in 2019) were considered for inclusion in the evaluation, subject to data availability and location. These models were augmented by government primary health clinics offering HIV services in similar locations. We conducted a cost-outcomes analysis by collecting patient-level resource usage and treatment outcomes through retrospective medical record reviews and a bottom-up micro-costing from the provider perspective (public or private payer). Patient outcomes were based on whether the patient was still in care at the end of the follow up period and viral load (VL) status, to create the following outcome categories: in care and responding (VL suppressed), in care and not responding (VL unsuppressed), in care (VL unknown) and not in care (LTFU or deceased). Data collection was conducted in 2019 and reflects services provided during the 4 years prior to that (2016–2019).

Results

Three hundred seventy-six patients were included across the five HIV treatment models. Across the three private sector models there were differences in the costs and outcomes of HIV treatment delivery, two of the models had results similar to the public sector primary health clinics. The nurse-led model appears to have a cost-outcome profile distinct from the others.

Conclusion

The results show that across the private sector models studied the costs and outcomes of HIV treatment delivery vary, yet there were models that provided costs and outcomes similar to those found with public sector delivery. Offering HIV treatment under NHI through private delivery models could therefore be an option to increase access beyond the current public sector capacity.
A self-monitoring wellbeing screening methodology for keyworkers, ‘My Personal Wellbeing’, using an integrative wellbeing model
Authors: Elvin Garry , Kurt Zeyneb , Kennedy Angela , Sice Petia , Walton Lee , Patel Paras
Published: March 2023

Background

The detrimental impact of Covid-19 has led to an urgent need to support the wellbeing of UK National Health Service and care workers. This research develops an online diary to support the wellbeing of staff in public healthcare in real-time, allowing the exploration of population wellbeing and pro-active responses to issues identified.

Methods

The diary was co-produced by NHS and care stakeholders and university researchers. It was based on an integrative model monitoring mental health symptoms as well as wellbeing indicators. Diary users were encouraged to reflect on their experience confidentially, empowering them to monitor their wellbeing. The data collected was analysed using Mann-Whitney-Wilcoxon and Kruskal-Wallis statistical tests to determine any significant wellbeing trends and issues.

Results

A statistically significant decline in wellbeing (P < 2.2E-16), and a significant increase in symptoms (P = 1.2E-14) was observed. For example, indicators of post-traumatic stress, including, flashbacks, dissociation, and bodily symptoms (Kruskal-Wallis P = 0.00081, 0.0083, and 0.027, respectively) became significantly worse and users reported issues with sleeping (51%), levels of alertness (46%), and burnout (41%).

Conclusions

The wellbeing diary indicated the value of providing ways to distinguish trends and wellbeing problems, thus, informing how staff wellbeing services can determine and respond to need with timely interventions. The results particularly emphasised the pressing need for interventions that help staff with burnout, self-compassion, and intrusive memories.
Infliximab versus ciclosporin in steroid resistant acute severe ulcerative colitis: a model-based cost-utility analysis of data from CONSTRUCT pragmatic trial
Authors: Alam Mohammed Fasihul , Longo Mirella , Cohen David , Groves Sam , Alrubaiy Laith , Hutchings Hayley A. , Watkins Alan , Sebastain Shaji , Williams John G.
Published: March 2023

Background

There is limited evidence in the literature on the long-term effectiveness and cost-effectiveness of treatments for Acute Severe Ulcerative Colitis (ASUC). The study aimed to perform decision analytic model-based long-term cost-utility analysis (CUA) of infliximab versus ciclosporin for steroid-resistant ASUC investigated in CONSTRUCT pragmatic trial.

Methods

A decision tree (DT) model was developed using two-year health effect, resource use and costs data from CONSTRUCT trial to estimate relative cost-effectiveness of two competing drugs from the United Kingdom (UK) National Health Services (NHS) perspective. Using short-term trial data, a Markov model (MM) was then developed and evaluated over further 18 years. Both DT and MM were combined to investigate cost-effectiveness of infliximab versus ciclosporin for ASUC patients over 20-year time horizon, with a rigorous multiple deterministic and probabilistic sensitivity analyses to address uncertainty in results.

Results

The decision tree mirrored trial-based results. Beyond 2-year trial follow-up, Markov model predicted a decrease in colectomy rate, but it remained slightly higher for ciclosporin. NHS costs and quality adjusted life years (QALYs) over base-case 20 year time horizon were £26,793 and 9.816 for ciclosporin and £34,185 and 9.106 for infliximab, suggesting ciclosporin dominates infliximab. Ciclosporin had 95% probability of being cost-effective at a willingness-to-pay (WTP) threshold value up to £20,000.

Conclusion

Using data from a pragmatic RCT, the cost-effectiveness models produced incremental net health benefit in favour of ciclosporin relative to infliximab. Results from long-term modelling indicated that ciclosporin remains dominant compared with infliximab for the treatment of NHS ASUC patients, however, these need to be interpreted cautiously.

Trial registration

CONSTRUCT Trial registration number ISRCTN22663589; EudraCT number: 2008-

001968-36 (Date 27/08/2008).
Level of job satisfaction and associated factors among rural health extension workers in Hadiya Zone, Southern Ethiopia
Authors: Tamene Abayneh , Tediso Dansamo , Gebretsadik Achamyelesh
Published: March 2023

Background

The improvement of various health outcomes, including the reduction of maternal, neonatal, infant, and child mortality as well as the increased use of maternity and newborn health services, was significantly assisted by rural health extension workers. Implementing health extension programs and offering the community high-quality healthcare services requires job satisfaction. In the study area, there has been little research on job satisfaction and related variables. Therefore, the purpose of this study was to evaluate the degree of job satisfaction among rural health extension workers in the Hadiya zone, Southern Ethiopia, as well as associated factors.

Methods

A facility-based cross-sectional study was conducted among 262 rural health extension workers from May 30, 2021, to July 02, 2021. A simple random sampling method was used to select six rural districts. Data were gathered utilizing structured interviewer-administered questions and skilled data collectors. EpiData V4.4.1 was used to store the data, and SPSS Version 25 was used for analysis. To determine the relationship between the variables, bivariate and multivariate logistic regressions were used. The association was reported using the adjusted odds ratio (AOR) with a 95% confidence interval (95%CI), and the significance level was set at a p-value of 0.05.

Results

This study showed that 52.7% of rural health extension workers were satisfied with their jobs. Support from Keble leaders [AOR = 5.3; 95% CI (2.6, 11.1)], on-job training [AOR = 5.7, 95% CI (2.2, 14.9)], supportive supervision [AOR = 4.3; 95% CI (1.7, 10.8)] and reward or recognition [AOR = 7.4, 95% CI (3.0, 18.1)] were factors that associated with job satisfaction of health extension workers.

Conclusion

According to this study, more than half of rural health extension workers were happy with their jobs. Health extension workers’ job satisfaction was affected by support from keble leaders, supportive supervision, on-the-job training, and recognition and rewards. In order to increase the happiness of the health extension workers, supporting supervision must be strengthened and the best performers must be recognized.
Maternal and perinatal outcomes in mixed antenatal care modality implementing telemedicine in the southwestern region of Colombia during the COVID-19 pandemic
Authors: Escobar María Fernanda , Gallego Juan Carlos , Echavarria María Paula , Fernandez Paula , Posada Leandro , Salazar Shirley , Gutierrez Isabella , Alarcon Juliana
Published: March 2023

Introduction

Contingency measures due to the COVID-19 pandemic limited access to routine prenatal care for pregnant women, increasing the risk of pregnancy complications due to poor prenatal follow-up, especially in those patients at high obstetric risk. This prompted the implementation and adaptation of telemedicine.

Objective

We aim to evaluate the maternal and perinatal outcomes of patients who received prenatal care in-person and by telemedicine.

Methods

We conducted a retrospective observational cohort study of pregnant women who received exclusive in-person and alternate (telemedicine and in-person) care from March to December 20,202, determining each group's maternal and neonatal outcomes.

Results

A total of 1078 patients were included, 156 in the mixed group and 922 in the in-person group. The patients in the mixed group had a higher number of prenatal controls (8 (6–9) vs 6 (4–8)p < 0.001), with an earlier gestational age at onset (7.1 (6–8.5) vs 9.3 (6.6–20.3),p < 0.001), however, they required a longer hospital stay (26 (16,67%) vs 86 (9,33%),p = 0.002) compared to those attended in-person; there were no significant differences in the development of obstetric emergencies, maternal death or neonatal complications.

Discussion

Incorporating telemedicine mixed with in-person care could be considered as an alternative for antenatal follow-up of pregnant women in low- and middle-income countries with barriers to timely and quality health care access.
Relationship between changes in the public health nurses’ workforce and the empirical Bayes estimates of standardized mortality ratio: a longitudinal ecological study of municipalities in Japan
Authors: Kodama Shimpei , Uwatoko Futoshi , Koriyama Chihaya
Published: March 2023

Background

The role of public health nurses (PHNs) in the community is expected to become increasingly important, along with the promotion of a comprehensive community care system. However, a comprehensive study of all municipalities is yet to be undertaken, and the relationship between the workforce of PHNs and health indicators is yet to be clarified. This study examined the effect of workforce change among PHNs, one of the structural indicators of PHNs’ activities regarding changes in the empirical Bayes estimate of standardized mortality ratios (EBSMRs).

Methods

An ecological study was conducted using municipality-level aggregate data. The data used were publicly available Japanese government statistics. The first-difference model of panel data analysis was used to examine the relationship between changes in EBSMR and changes in the number of PHNs per 100,000 population from 2010 to 2015, adjusting for the effects of population and other healthcare resources, including the number of physicians, medical clinics, general hospitals, and welfare facilities. The variation by the 47 prefectures was added to the linear model as a random effect. We also performed a sensitivity analysis using the full Bayesian inference using the Besag-York-Mollie model.

Results

For males, EBSMRs for all causes and malignant neoplasms significantly decreased with an increase in the number of PHNs per population (coefficients: -1.00 and -0.89,pvalues: 0.008 and 0.043, respectively). For females, although all EBSMRs except malignant neoplasms showed decreased tendencies due to the increase in the number of PHNs per population, none of them were significant. The full Bayesian inference confirmed these associations.

Conclusions

An increase in the number of PHNs per population was significantly associated with a greater reduction in deaths from all causes and malignant neoplasms in males. The results of the full Bayesian inference also suggest that the workforce of PHNs may be related to changes in standardized mortality ratios for deaths from all causes in females.
Genetic architecture of a pollinator shift and its fate in secondary hybrid zones of two Petunia species
Authors: Binaghi Marta , Esfeld Korinna , Mandel Therese , Freitas Loreta B. , Roesti Marius , Kuhlemeier Cris
Published: March 2023

Background

Theory suggests that the genetic architecture of traits under divergent natural selection influences how easily reproductive barriers evolve and are maintained between species. Divergently selected traits with a simple genetic architecture (few loci with major phenotypic effects) should facilitate the establishment and maintenance of reproductive isolation between species that are still connected by some gene flow. While empirical support for this idea appears to be mixed, most studies test the influence of trait architectures on reproductive isolation only indirectly.Petuniaplant species are, in part, reproductively isolated by their different pollinators. To investigate the genetic causes and consequences of this ecological isolation, we deciphered the genetic architecture of three floral pollination syndrome traits in naturally occurring hybrids between the widespreadPetunia axillarisand the highly endemic and endangeredP. exserta.

Results

Using population genetics, Bayesian linear mixed modelling and genome-wide association studies, we found that the three pollination syndrome traits vary in genetic architecture. Few genome regions explain a majority of the variation in flavonol content (defining UV floral colour) and strongly predict the trait value in hybrids irrespective of interspecific admixture in the rest of their genomes. In contrast, variation in pistil exsertion and anthocyanin content (defining visible floral colour) is controlled by many genome-wide loci. Opposite to flavonol content, the genome-wide proportion of admixture between the two species predicts trait values in their hybrids. Finally, the genome regions strongly associated with the traits do not show extreme divergence between individuals representing the two species, suggesting that divergent selection on these genome regions is relatively weak within their contact zones.

Conclusions

Among the traits analysed, those with a more complex genetic architecture are best maintained in association with the species upon their secondary contact. We propose that this maintained genotype–phenotype association is a coincidental consequence of the complex genetic architectures of these traits: some of their many underlying small-effect loci are likely to be coincidentally linked with the actual barrier loci keeping these species partially isolated upon secondary contact. Hence, the genetic architecture of a trait seems to matter for the outcome of hybridization not only then when the trait itself is under selection.
The association between menstrual cycle characteristics and cardiometabolic outcomes in later life: a retrospective matched cohort study of 704,743 women from the UK
Authors: Okoth Kelvin , Smith William Parry , Thomas G. Neil , Nirantharakumar Krishnarajah , Adderley Nicola J.
Published: March 2023

Background

Female reproductive factors are gaining prominence as factors that enhance cardiovascular disease (CVD) risk; nonetheless, menstrual cycle characteristics are under-recognized as a factor associated with CVD. Additionally, there is limited data from the UK pertaining to menstrual cycle characteristics and CVD risk.

Methods

A UK retrospective cohort study (1995–2021) using data from a nationwide database (The Health Improvement Network). Women aged 18–40 years at index date were included. 252,325 women with history of abnormal menstruation were matched with up to two controls. Two exposures were examined: regularity and frequency of menstrual cycles; participants were assigned accordingly to one of two separate cohorts. The primary outcome was composite cardiovascular disease (CVD). Secondary outcomes were ischemic heart disease (IHD), cerebrovascular disease, heart failure (HF), hypertension, and type 2 diabetes mellitus (T2DM). Cox proportional hazards regression models were used to derive adjusted hazard ratios (aHR) of cardiometabolic outcomes in women in the exposed groups compared matched controls.

Results

During 26 years of follow-up, 20,605 cardiometabolic events occurred in 704,743 patients. Compared to women with regular menstrual cycles, the aHRs (95% CI) for cardiometabolic outcomes in women with irregular menstrual cycles were as follows: composite CVD 1.08 (95% CI 1.00–1.19), IHD 1.18 (1.01–1.37), cerebrovascular disease 1.04 (0.92–1.17), HF 1.30 (1.02–1.65), hypertension 1.07 (1.03–1.11), T2DM 1.37 (1.29–1.45). The aHR comparing frequent or infrequent menstrual cycles to menstrual cycles of normal frequency were as follows: composite CVD 1.24 (1.02–1.52), IHD 1.13 (0.81–1.57), cerebrovascular disease 1.43 (1.10–1.87), HF 0.99 (0.57–1.75), hypertension 1.31 (1.21–1.43), T2DM 1.74 (1.52–1.98).

Conclusions

History of either menstrual cycle irregularity or frequent or infrequent cycles were associated with an increased risk of cardiometabolic outcomes in later life. Menstrual history may be a useful tool in identifying women eligible for periodic assessment of their cardiometabolic health.
The association of gestational age and birthweight with blood pressure, cardiac structure, and function in 4 years old: a prospective birth cohort study
Authors: Du Bowen , Wang Hualin , Wu Yujian , Li Zhuoyan , Niu Yiwei , Wang Qianchuo , Zhang Lin , Chen Sun , Wu Yurong , Huang Jihong , Sun Kun , Wang Jian
Published: March 2023

Background

Current evidence relating birthweight and gestational age to cardiovascular risk is conflicting. Whether these factors have independent or interactive impacts on cardiovascular parameters during early childhood remains unclear. The goal of this study was to explore whether there were any independent and interactive effects of gestational age and birthweight on blood pressure, left ventricle (LV) structure, and function in 4 years old.

Methods

This study included 1194 children in the Shanghai Birth Cohort from 2013 to 2016. Information about the mothers and children was recorded at time of birth using a questionnaire. Follow-up measurements, including anthropometric, blood pressure, and echocardiography, were taken between 2018 and 2021, when the children were 4 years old. Multiple linear or logistic regressions and restricted cubic spline were used to explore the association of birthweight and gestational age with cardiovascular measurements.

Results

Gestational age had a significant negative correlation with both systolic blood pressure [β =  − 0.41, 95% CI: (− 0.76, − 0.07)] and mean arterial pressure [β =  − 0.36, 95%CI: (− 0.66, − 0.07)]. The risk of prehypertension decreased with increased gestational age [OR = 0.54, 95% CI: (0.32, 0.93)]. The relationship between birthweight with blood pressure was U-shape (P for non-linear < 0.001). The wall thickness, volume, mass, and cardiac output of LV increased with birthweight, though the ejection fraction [β =  − 1.02, 95% CI: (− 1.76, − 0.27)] and shorten fraction [β = 0.72, 95% CI: (− 1.31, − 0.14)] decreased with birthweight. The risk of LV hypertrophy was not associated with birthweight [OR = 1.59, 95% CI: (0.68, 3.73)].

Conclusions

In this study, we found different associations of birthweight and gestational age with cardiovascular measurements in the offspring at 4 years old. Gestational age influenced blood pressure independent of birthweight. Heart size and function at 4 years old was influenced mostly by birthweight and not by gestational age.
Safety, tolerability, pharmacokinetics, and antiviral activity of the novel core protein allosteric modulator ZM-H1505R (Canocapavir) in chronic hepatitis B patients: a randomized multiple-dose escalation trial
Authors: Jia Haiyan , Mai Jiajia , Wu Min , Chen Hong , Li Xiaojiao , Li Cuiyun , Liu Jingrui , Liu Chengjiao , Hu Yue , Zhu Xiaoxue , Jiang Xiuhong , Hua Bo , Xia Tian , Liu Gang , Deng Aiyun , Liang Bo , Guo Ruoling , Lu Hui , Wang Zhe , Chen Huanming , Zhang Zhijun , Zhang Hong , Niu Junqi , Ding Yanhua
Published: March 2023

Background

Hepatitis B virus (HBV) core protein-targeting antivirals (CpTAs) are promising therapeutic agents for treating chronic hepatitis B (CHB). In this study, the antiviral activity, pharmacokinetics (PK), and tolerability of ZM-H1505R (Canocapavir), a chemically unique HBV CpTA, were evaluated in patients with CHB.

Methods

This study was a double-blind, randomized, placebo-controlled phase 1b trial in Chinese CHB patients. Noncirrhotic and treatment-naive CHB patients were divided into three cohorts (10 patients per cohort) and randomized within each cohort in a ratio of 4:1 to receive a single dose of 50, 100, or 200 mg of Canocapavir or placebo once a day for 28 consecutive days.

Results

Canocapavir was well tolerated, with the majority of adverse reactions being grade I or II in severity. There were no serious adverse events, and no patients withdrew from the study. Corresponding to 50, 100, and 200 mg doses of Canocapavir, the mean plasma trough concentrations of the drug were 2.7-, 7.0-, and 14.6-fold of its protein-binding adjusted HBV DNA EC50 (135 ng/mL), respectively, with linear PK and a low-to-mild accumulation rate (1.26–1.99). After 28 days of treatment, the mean maximum HBV DNA declines from baseline were -1.54, -2.50, -2.75, and -0.47 log10 IU/mL for the 50, 100, and 200 mg of Canocapavir or placebo groups, respectively; and the mean maximum pregenomic RNA declines from baseline were -1.53, -2.35, -2.34, and -0.17 log10 copies/mL, respectively.

Conclusions

Canocapavir treatment is tolerated with efficacious antiviral activity in CHB patients, supporting its further development in treating HBV infection.

Trial registration

ClinicalTrials.gov, number NCT05470829).
Life expectancy among older adults with or without frailty in China: multistate modelling of a national longitudinal cohort study
Authors: Gao Junling , Wang Yujie , Xu Jixiang , Jiang Junjia , Yang Shitong , Xiao Qianyi
Published: March 2023

Background

Little is known about life expectancy (LE) with or without frailty. We aimed to estimate the total LE and duration of the state of frailty in China.

Methods

This study included older adults aged 65 years and older from the Chinese Longitudinal Healthy Longevity Study (CLHLS). Frailty status was classified into robust, pre-frailty and frailty based on a cumulative deficit model. Total and specific frailty state LEs at 65 years of age were estimated and stratified by demographic characteristics, behaviours, and psychosocial factors using continuous-time multistate modelling.

Results

The total LE of older adults aged 65 years in China was 14.74 years on average (95% CI: 14.52–14.94), of which 4.18 years (95% CI: 4.05–4.30) were robust, 7.46 years (95% CI: 7.31–7.61) pre-frail and 3.10 years (95% CI: 3.01–3.20) frail. Older adults with higher robust LE included men (4.71 years, 95% CI: 4.56–4.88), married older adults (4.41 years, 95% CI: 4.27–4.56), those engaging in physical activity (4.41 years, 95% CI: 4.23–4.59), those consuming fruits daily (4.48 years, 95% CI: 4.22–4.77) and those with high social participation (4.39 years, 95% CI: 4.26–4.53). Increased educational attainment were gradually associated with increased robust LE.

Conclusions

Frailty may lead to a reduced total LE and robust LE of older adults in China. In addition to finding inequalities in total and robust LEs by socioeconomic status, our findings also highlight that healthy behaviours and social participation may ease frailty-related reductions in total and robust LE. Our findings imply that national life-course strategies aimed at frailty screening and psychosocial and behavioural interventions could be important for health aging in China.
Identification of potential ferroptosis hub genes in acute-on-chronic liver failure based on bioinformatics analysis and experimental verification
Authors: Kuang Meixia , Cai Longhui , Zhao Jing , Huang Liqiao , Ji Yichun , Lv Bingyao , Kuang Weihong
Published: March 2023

Background

Ferroptosis plays an important role in the development of acute-on-chronic liver failure (ACLF). The present project aimed to identify and validate the potential ferroptosis-related genes in ACLF by bioinformatics analysis and experimental verification.

Materials and methods

The GSE139602 dataset was obtained from the Gene Expression Omnibus database and intersected with ferroptosis genes. Ferroptosis-related differentially expressed genes (DEGs) between the ACLF tissue and healthy group were analyzed using bioinformatics methods. Analysis of enrichment, protein‒protein interactions, and hub genes was conducted. Potential drugs targeting these hub genes were retrieved from the DrugBank database. Finally, we performed real-time quantitative PCR (RT-qPCR) to validate the expression of the hub genes.

Results

A total of 35 ferroptosis-related DEGs were screened, which were enriched in the biosynthesis of amino acids, peroxisomes, fluid shear stress and atherosclerosis. PPI network analysis indicated five ferroptosis-related hub genes, namely, HRAS, TXNRD1, NQO1, PSAT1, and SQSTM1. The experimental validation indicated that the expression levels of HRAS, TXNRD1, NQO1, and SQSTM1 were lower, while the expression level of PSAT1 was higher in ACLF model rats than in healthy rats.

Conclusions

Our findings reveal that PSAT1, TXNRD1, HRAS, SQSTM1 and NQO1 may affect the development of ACLF by regulating ferroptotic events. These results provide a valid reference for potential mechanisms and identification in ACLF.
A retrospective analysis of MS/MS screening for IEM in high-risk areas
Authors: He Xiao , Kuang Juan , Lai Jiahong , Huang Jingxiong , Wang Yijin , Lan Guofeng , Xie Yingjun , Shi Xuekai
Published: March 2023

Inborn errors of metabolism (IEM) can lead to severe motor and neurological developmental disorders and even disability and death in children due to untimely treatment. In this study, we used tandem mass spectrometry (MS/MS) for primary screening and recall of those with positive primary screening for rescreening. Further diagnosis was based on biochemical tests, imaging and clinical presentation as well as accurate genetic testing using multi-gene panel with high-throughput sequencing of 130 IEM-related genes. The screening population was 16,207 newborns born between July 1, 2019, and December 31, 2021. Based on the results, 8 newborns were diagnosed with IEM, constituting a detection rate of 1:2,026. Phenylketonuria was the most common form of IEM. In addition, seven genes associated with IEM were detected in these eight patients. All eight patients received standardized treatment starting in the neonatal period, and the follow-up results showed good growth and development. Therefore, our study suggests that MS/MS rescreening for IEM pathogenic variants in high-risk areas, combined with a sequencing validation strategy, can be highly effective in the early detection of affected children. This strategy, combined with early intervention, can be effective in preventing neonatal morbidity and improving population quality.
The emerging role of the piRNA/PIWI complex in respiratory tract diseases
Authors: Yao Yizhu , Li Yaozhe , Zhu Xiayan , Zhao Chengguang , Yang Lehe , Huang Xiaoying , Wang Liangxing
Published: March 2023

PIWI-interacting RNA (piRNA) is a class of recently discovered small non-coding RNA molecules with a length of 18–33 nt that interacts with the PIWI protein to form the piRNA/PIWI complex. The PIWI family is a subfamily of Argonaute (AGO) proteins that also contain the AGO family which bind to microRNA (miRNA). Recently studies indicate that piRNAs are not specific to in the mammalian germline, they are also expressed in a tissue-specific manner in a variety of human tissues and participated in various of diseases, such as cardiovascular, neurological, and urinary tract diseases, and are especially prevalent in malignant tumors in these systems. However, the functions and abnormal expression of piRNAs in respiratory tract diseases and their underlying mechanisms remain incompletely understood. In this review, we discuss current studies summarizing the biogenetic processes, functions, and emerging roles of piRNAs in respiratory tract diseases, providing a reference value for future piRNA research.
Weight loss and outcomes in subjects with progressive pulmonary fibrosis: data from the INBUILD trial
Authors: Kreuter Michael , Bendstrup Elisabeth , Jouneau Stéphane , Maher Toby M. , Inoue Yoshikazu , Miede Corinna , Lievens Dirk , Crestani Bruno
Published: March 2023

Background

Lower body mass index (BMI) and weight loss have been associated with worse outcomes in some studies in patients with pulmonary fibrosis. We analyzed outcomes in subgroups by BMI at baseline and associations between weight change and outcomes in subjects with progressive pulmonary fibrosis (PPF) in the INBUILD trial.

Methods

Subjects with PPF other than idiopathic pulmonary fibrosis were randomized to receive nintedanib or placebo. In subgroups by BMI at baseline (< 25, ≥ 25 to < 30, ≥ 30 kg/m2), we analyzed the rate of decline in FVC (mL/year) over 52 weeks and time-to-event endpoints indicating disease progression over the whole trial. We used a joint modelling approach to assess associations between change in weight and the time-to-event endpoints.

Results

Among 662 subjects, 28.4%, 36.6% and 35.0% had BMI < 25, ≥ 25 to < 30 and ≥ 30 kg/m2, respectively. The rate of decline in FVC over 52 weeks was numerically greater in subjects with baseline BMI < 25 than ≥ 25 to < 30 or ≥ 30 kg/m2 (nintedanib: − 123.4, − 83.3, − 46.9 mL/year, respectively; placebo: − 229.5; − 176.9; − 171.2 mL/year, respectively). No heterogeneity was detected in the effect of nintedanib on reducing the rate of FVC decline among these subgroups (interaction p = 0.83). In the placebo group, in subjects with baseline BMI < 25, ≥ 25 to < 30 and ≥ 30 kg/m2, respectively, 24.5%, 21.4% and 14.0% of subjects had an acute exacerbation or died, and 60.2%, 54.5% and 50.4% of subjects had ILD progression (absolute decline in FVC % predicted ≥ 10%) or died over the whole trial. The proportions of subjects with these events were similar or lower in subjects who received nintedanib versus placebo across the subgroups. Based on a joint modelling approach, over the whole trial, a 4 kg weight decrease corresponded to a 1.38-fold (95% CI 1.13, 1.68) increase in the risk of acute exacerbation or death. No association was detected between weight loss and the risk of ILD progression or the risk of ILD progression or death.

Conclusions

In patients with PPF, lower BMI at baseline and weight loss may be associated with worse outcomes and measures to prevent weight loss may be required.

Trial registration:https://clinicaltrials.gov/ct2/show/NCT02999178.
Surface electromyography to quantify neuro-respiratory drive and neuro-mechanical coupling in mechanically ventilated children
Authors: Koopman Alette A. , van Dijk Jefta , Oppersma Eline , Blokpoel Robert G. T. , Kneyber Martin C. J.
Published: March 2023

Background

The patient’s neuro-respiratory drive, measured as electrical activity of the diaphragm (EAdi), quantifies the mechanical load on the respiratory muscles. It correlates with respiratory effort but requires a dedicated esophageal catheter. Transcutaneous (surface) monitoring of respiratory muscle electromyographic (sEMG) signals may be considered a suitable alternative to EAdi because of its non-invasive character, with the additional benefit that it allows for simultaneously monitoring of other respiratory muscles. We therefore sought to study the neuro-respiratory drive and timing of inspiratory muscles using sEMG in a cohort of children enrolled in a pediatric ventilation liberation trial. The neuro-mechanical coupling, relating the pressure generated by the inspiratory muscles to the sEMG signals of these muscles, was also calculated.

Methods

This is a secondary analysis of data from a randomized cross-over trial in ventilated patients aged < 5 years. sEMG recordings of the diaphragm and parasternal intercostal muscles (ICM), esophageal pressure tracings and ventilator scalars were simultaneously recorded during continuous spontaneous ventilation and pressure controlled-intermittent mandatory ventilation, and at three levels of pressure support. Neuro-respiratory drive, timing of diaphragm and ICM relative to the mechanical ventilator’s inspiration and neuro-mechanical coupling were quantified.

Results

Twenty-nine patients were included (median age: 5.9 months). In response to decreasing pressure support, both amplitude of sEMG (diaphragm: p = 0.001 and ICM: p = 0.002) and neuro-mechanical efficiency indices increased (diaphragm: p = 0.05 and ICM: p < 0.001). Poor correlations between neuro-respiratory drive and respiratory effort were found, with R2: 0.088 [0.021–0.152].

Conclusions

sEMG allows for the quantification of the electrical activity of the diaphragm and ICM in mechanically ventilated children. Both neuro-respiratory drive and neuro-mechanical efficiency increased in response to lower inspiratory assistance. There was poor correlation between neuro-respiratory drive and respiratory effort.

Trial registration

ClinicalTrials.gov ID NCT05254691. Registered 24 February 2022, registered retrospectively.