bluuebunny/crossref_metadata_2025 huggingface dataset:
A tool to define and measure maternal healthcare acceptability at a selected health sub-district in South Africa
Authors: Bucyibaruta Joy Blaise , Peu Mmapheko Doriccah , Bamford Lesley , Musekiwa Alfred
Published: April 2023

Background

There are many factors during pregnancy and labor that influence women’s acceptability of maternal healthcare. Nevertheless, the concept of acceptability of maternal healthcare has unfortunately not been clearly defined and remains difficult to assess, affecting its implications and approaches from maternal health perspectives. In this study, we proposed a practical definition of maternal healthcare acceptability and developed a tool to measure maternal healthcare acceptability from patients’ perspective at a selected health sub-district in South Africa.

Methods

We applied known techniques to develop measurement tools in health settings. The concept development drew from the literature review leading to the proposed definition of maternal healthcare acceptability which was then refined and validated by experts through Delphi technique. Other techniques included specification of concept constructs; selection of indicators; formation of indices; measurement tool/scale construction; and testing of reliability and validity. Factor analysis and simple arithmetic equation were performed on secondary and primary datasets respectively.

Results

Experts in the field reached a consensual definition of maternal healthcare acceptability. Factor analysis revealed three factors retained to predict maternal healthcare acceptability indices, namely provider, healthcare and community. Structural equation model showed good fit (CFI = 0.97), with good reliability and validity. Hypothesis testing confirmed that items and their corresponding factors were related (p < 0.01). Simple arithmetic equation was recommended as alternative method to measure acceptability when factor analysis was not applicable.

Conclusion

This study provides new insights into defining and measuring acceptability of maternal healthcare with significant contributions on existing theories and practices on this topic and practical applications not only for maternal health but also across diverse health disciplines.
Office blood pressure versus ambulatory blood pressure measurement in childhood obesity
Authors: van der Heijden Laila B , Groothoff Jaap W. , Feskens Edith JM , Janse Arieke J
Published: April 2023

Background

The prevalence of obesity-related co-morbidities is rising parallel to the childhood obesity epidemic. High blood pressure (BP), as one of these co-morbidities, is detected nowadays at increasingly younger ages. The diagnosis of elevated BP and hypertension, especially in the childhood population, presents a challenge to clinicians. The added value of ambulatory blood pressure measurement (ABPM) in relation to office blood pressure (OBP) measurements in obese children is unclear. Furthermore, it is unknown how many overweight and obese children have an abnormal ABPM pattern. In this study we evaluated ABPM patterns in a population of overweight and obese children and adolescents, and compared these patterns with regular OBP measurements.

Methods

In this cross-sectional study in overweight or obese children and adolescents aged 4–17 years who were referred to secondary pediatric obesity care in a large general hospital in The Netherlands, OBP was measured during a regular outpatient clinic visit. Additionally, all participants underwent a 24-hour ABPM on a regular week-day. Outcome measures were OBP, mean ambulatory SBP and DBP, BP load (percentage of readings above the ambulatory 95th blood pressure percentiles), ambulatory BP pattern (normal BP, white-coat hypertension, elevated BP, masked hypertension, ambulatory hypertension), and BP dipping.

Results

We included 82 children aged 4–17 years. They had a mean BMI Z-score of 3.3 (standard deviation 0.6). Using ABPM, 54.9% of the children were normotensive (95% confidence interval 44.1–65.2), 26.8% had elevated BP, 9.8% ambulatory hypertension, 3.7% masked hypertension, and 4.9% white-coat hypertension. An isolated night-time BP load > 25% was detected in almost a quarter of the children. 40% of the participants lacked physiologic nocturnal systolic BP dipping. In the group of children with normal OBP, 22.2% turned out to have either elevated BP or masked hypertension on ABPM.

Conclusions

In this study a high prevalence of abnormal ABPM patterns in overweight or obese children and adolescents was detected. Additionally, OBP poorly correlated with the child’s actual ABPM pattern. Herewith, we emphasized the usefulness of ABPM as an important diagnostic tool in this population.
Active monitoring versus an abduction device for treatment of infants with centered dysplastic hips: study protocol for a randomized controlled trial (TReatment with Active Monitoring (TRAM)-Trial)
Authors: Mulder Frederike E. C. M. , Witlox M. Adhiambo , Dirksen Carmen D. , de Witte Pieter Bas , de Vos-Jakobs Suzanne , Ham Arno M. ten , Witbreuk Melinda M. E. H. , Sakkers Ralph , Drongelen Magritha M. H. P. Foreman-van , Robben Simon G. F. ,   TRAM-Trial Consortium, van Bergen Christiaan J. A. , Besselaar Arnold T. , Boot Marieke , Burger Bart J. , van Douveren Florens Q. M. P. , van Gelder J. H. , Hartog Yvon M.den , Oost Iris Koenraadt-van , van Linge Joost H. , Maathuis Patrick G. M. , Moerman Sophie , Pereboom Renske M. , Staal Heleen M. , van der Steen M. C. , Tolk Jaap J. , Vergroesen Diederik A. , Zeegers A. V. C. M. , Mathijssen Nina M. C.
Published: April 2023

Background

Developmental Dysplasia of the Hip (DDH) is one of the most common pediatric orthopedic disorders, affecting 1–3% of all newborns. The optimal treatment of centered DDH is currently under debate. This randomized controlled trial aims to study the (cost-)effectiveness of active monitoring versus abduction treatment for infants with centered DDH.

Methods

This is a multicenter, parallel-group, open-label, non-inferiority randomized controlled trial studying the (cost-)effectiveness of active monitoring versus abduction treatment for infants with centered DDH in fourteen hospitals in the Netherlands. In total, 800 infants with centered DDH (Graf IIa-/IIb/IIc), aged 10–16 weeks, will be randomly allocated to the active monitoring or abduction treatment group. Infants will be followed up until the age of 24 months. The primary outcome is the rate of normal hips, defined as an acetabular index lower than 25 degrees on an antero-posterior radiograph, at the age of 12 months. Secondary outcomes are the rate of normal hips at the age of 24 months, complications, time to hip normalization, the relation between baseline patient characteristics and the rate of normal hips, compliance, costs, cost-effectiveness, budget impact, health-related quality of life (HRQoL) of the infant, HRQoL of the parents/caregivers, and parent/caregiver satisfaction with the treatment protocol.

Discussion

The outcomes of this randomized controlled trial will contribute to improving current care-as-usual for infants with centered DDH.

Trial registration

Dutch Trial Register, NL9714, registered September 6, 2021. https://clinicaltrialregister.nl/en/trial/29596
JAGN1 mutation with distinct clinical features; two case reports and literature review
Authors: Hojabri Mahsa , Farsi Yeganeh , Jamee Mahnaz , Abolhassani Hassan , Khani Hedieh Haji Khodaverdi , Karimi Abdollah , Mesdaghi Mehrnaz , Chavoshzadeh Zahra , Sharafian Samin
Published: April 2023

Jagunal homolog 1 (JAGN1) has been recognized as an essential protein in neutrophil function. The mutated JAGN1 is responsible for immunodeficiency related to innate and humoral defense mechanisms. This deficiency impairs neutrophil development and function, leading to recurrent infections and facial dysmorphism as phenotypic consequences of severe congenital neutropenia (SCN). We report two siblings having the reportedJAGN1mutation with different clinical manifestations. Recurrent abscess formation unresponsive to antibiotic therapy, a history of delayed umbilical separation, frequent bacterial or fungal infection, dysmorphic face, failure to thrive, and other coexisting organ abnormalities should prompt physicians to syndromic immunodeficiencies involving neutrophils. Genetic investigations to elucidate the responsible mutation is critical as clinical management varies. Once the diagnosis is confirmed, a multi-disciplinary team should perform further workups to investigate other coexisting malformations and neurodevelopmental evaluation.
Relationship between cognitive functioning and physical fitness in regard to age and sex
Authors: González-Fernández Francisco Tomás , Delgado-García Gabriel , Coll Jesús Siquier , Silva Ana Filipa , Nobari Hadi , Clemente Filipe Manuel
Published: April 2023

The aim of this study was to analyze the relationships among physical cognitive ability, academic performance, and physical fitness regarding age and sex in a group of 187 students (53.48% male, 46.52% female) from one town of Norwest of Jaén, Andalusia (Spain), aged between 9 and 15 years old (M = 11.97, SD = 1.99). The D2 attention test was used in order to analyze selective attention and concentration. Physical fitness, reflected on maximal oxygen uptake (VO2max), was evaluated using the 6 min Walking Test (6MWT). The analysis taken indicated a significant relationship between physical fitness level, attention, and concentration, as in the general sample looking at sex (finding differences between boys and girls in some DA score in almost all age categories [p < 0.05]) and at age category (finding some differences between the younger age category groups and the older age category groups in some DA scores (p < 0.05), not finding any significant interaction between sex and age category (p > 0.05). In sum, the present study revealed that students with better aerobic fitness can present better-processed elements and smaller omission errors. Moreover, girls and older students seem to present better cognitive functioning scores than boys and younger. Our findings suggest that more research is necessary to elucidate the cognitive function between ages, sexes, and physical fitness and anthropometry levels of students.
The effect of azithromycin on sputum inflammatory markers in bronchiectasis
Authors: Terpstra L. C. , Altenburg J. , Doodeman H. J. , Piñeros Y. S. Sabogal , Lutter R. , Heijerman H. G. M. , Boersma W. G.
Published: April 2023

Background

Long term macrolide treatment has been found beneficial in bronchiectasis (BE) -pathogical bronchial dilatation- possibly due to a combined anti-bacterial and immunomodulatory effect. The exact mechanism of inflammatory response is unknown. Here, we investigated the effect of maintenance macrolide treatment on the inflammatory response in BE. In addition, we assessed the inflammatory profile in BE in relation to disease severity.

Methods

During the BAT randomized controlled trial (investigating the effect of 1 year of azithromycin (AZM) in 83 BE patients), data on BE severity, lung function and sputum microbiology was collected. For the current study, a wide range of inflammatory markers were analysed in 3- monthly sputum samples in all participants.

Results

At baseline, marked neutrophilic but also eosinophilic inflammation was present in both groups, which remained stable throughout the study and was not affected by AZM treatment. Significant upregulation of pro-inflammatory markers correlated with FEV1 < 50% (TNFα, ECP, IL-21, IL-1, p = 0.01- 0.05), H. influenzae (HI) colonization (MPO, ECP, MIP-1, TNFα, IL-21, Il-8, IL-1, IL-1α, p < 0.001 – 0.04) and number of exacerbations (MPO, ECP, VEGF, MMP-9, p = 0.003 – 0.01). Surprisingly, colonization with P. aeruginosa (PA) was found to correlate with an attenuated inflammatory response compared to non-PA colonized. In placebo-treated patients, presence of an infectious exacerbation was reflected by a significant excessive increase in inflammation as compared to a non-significant upregulation in the AZM-treated patients.

Conclusion

One year of AZM treatment did not result in attenuation of the inflammatory response in BE. Increasing disease severity and the presence of an exacerbation were reflected by upregulation of pro-inflammatory markers.
Reducing complications of femoral neck fracture management: a retrospective study on the application of multidisciplinary team
Authors: Liang Weiming , Qin Gang , Yu Lizhi , Wang Yingying
Published: April 2023

Background

Femoral neck fractures are associated with substantial morbidity and mortality for older adults. Multi-system medical diseases and complications can lead to long-term care needs, functional decline and death, so patients sustaining hip fractures usually have comorbid conditions that may benefit from application of multidisciplinary team(MDT).

Methods

This is a retrospective cohort study that incorporates medical record review with an outcomes management database. 199 patients were included who had surgery for a new unilateral femoral neck fracture from January 2018 to December 2021 (96 patients in usual care (UC) model and 103 patients in MDT model. High-energy, pathological, old and periprosthetic femoral neck fracture were excluded. Age, gender, comorbidity status, time to surgery, and postoperative complication, length of stay, in-hospital mortality, 30-day readmission rate, 90-day mortality data were collected and analyzed.

Results

Preoperative general data of sex, age, community dwelling and charlson comorbidity score of MDT group (n = 103) have no statistically significant difference with that of usual care (UC) group. Patients treated in the MDT model had significantly shorter times to surgery (38.5 vs. 73.4 h;P = 0.028) and lower lengths of stay (11.5 vs. 15.2 days;P = 0.031). There were no significant differences between two models in In-hospital mortality (1.0% vs. 2.1%; P = 0.273), 30-day readmission rate (7.8% vs. 11.5%; P = 0.352) and 90-day mortality (2.9% vs. 3.1%; P = 0.782). The MDT model had fewer complications overall (16.5% vs. 31.3%; P = 0.039), with significantly lower risks of delirium, postoperative infection, bleeding, cardiac complication, hypoxia, and thromboembolism.

Conclusion

Application of MDT can provide standardized protocols and a total quality management approach, leading to fewer complications for elderly patients with femoral neck fracture.

Trial registration

No.
Performing a sperm DNA fragmentation test in addition to semen examination based on the WHO criteria can be a more accurate diagnosis of IVF outcomes
Authors: Okubo Tsuyoshi , Onda Noriyuki , Hayashi Teruaki , Kobayashi Tatsuya , Omi Kenji , Segawa Tomoya
Published: April 2023

Background

We analyzed the sperm DNA fragmentation index (DFI) and general semen test based on the World Health Organization (WHO) criteria and compared the two tests using semen factors. In addition, we examined whether DFI is a reliable parameter associated with in vitro fertilization (IVF) outcomes.

Methods

Sperm chromatin dispersion (SCD) and general semen tests were conducted in accordance with the WHO 2010 guidelines, and correlations between the two tests were investigated. The WHO criteria were set as the cutoff values for each of the following factors: semen volume, concentration, total sperm count, motility, and normal morphology, and compared with the DFI results.

Results

The subjects had a mean sperm DFI of 15.3% ± 12.6%, and the DFI increased with age. In contrast, motility and normal morphology decreased as the DFI increased. Patients who satisfied the WHO criteria in terms of concentration, total sperm count, and motility had a significantly lower DFI than those who did not satisfy the criteria. Therefore, evaluation with a general semen test based on the WHO criteria should be regarded as a qualitative evaluation of all factors other than semen volume and normal morphology.

Conclusions

High DFI (≥ 30%) caused a low blastocyst development rate following intracytoplasmic sperm injection. Male infertility due to DFI should be suspected when IVF results are poor despite normal semen findings based on the WHO criteria. The results of this study suggest that the SCD test may more accurately evaluate the correlation between IVF clinical outcomes and male infertility. Therefore, it is important to focus on DFI measurements.
Indicators of integrating oral health care within universal health coverage and general health care in low-, middle-, and high-income countries: a scoping review
Authors: Jashni Yassaman Karimi , Emari Fatemeh , Morris Martin , Allison Paul
Published: April 2023

Background

The World Health Organization (WHO) has recently devoted special attention to oral health and oral health care recommending the latter becoming part of universal health coverage (UHC) so as to reduce oral health inequalities across the globe. In this context, as countries consider acting on this recommendation, it is essential to develop a monitoring framework to measure the progress of integrating oral health/health care into UHC. This study aimed to identify existing measures in the literature that could be used to indicate oral health/health care integration within UHC across a range of low-, middle- and high-income countries.

Methods

A scoping review was conducted by searching MEDLINE via Ovid, CINAHL, and Ovid Global Health databases. There were no quality or publication date restrictions in the search strategy. An initial search by an academic librarian was followed by the independent reviewing of all identified articles by two authors for inclusion or exclusion based on the relevance of the work in the articles to the review topic. The included articles were all published in English. Articles concerning which the reviewers disagreed on inclusion or exclusion were reviewed by a third author, and subsequent discussion resulted in agreement on which articles were to be included and excluded. The included articles were reviewed to identify relevant indicators and the results were descriptively mapped using a simple frequency count of the indicators.

Results

The 83 included articles included work from a wide range of 32 countries and were published between 1995 and 2021. The review identified 54 indicators divided into 15 categories. The most frequently reported indicators were in the following categories: dental service utilization, oral health status, cost/service/population coverage, finances, health facility access, and workforce and human resources. This study was limited by the databases searched and the use of English-language publications only.

Conclusions

This scoping review identified 54 indicators in a wide range of 15 categories of indicators that have the potential to be used to evaluate the integration of oral health/health care into UHC across a wide range of countries.
The effect of dentin surface pretreatment using dimethyl sulfoxide on the bond strength of a universal bonding agent to dentin
Authors: Mirzaei Kianoosh , Ahmadi Elham , Rafeie Niyousha , Abbasi Mahdi
Published: April 2023

Background

This study aimed to evaluate the effect of dentin pretreatment by Dimethyl Sulfoxide (DMSO) on the bond strength and microleakage of a universal bonding agent to dentin.

Methods

Fifty-six dentinal discs (thickness = 2 mm) were obtained from the crowns of the human third molars. The disks were assigned into 4 groups and treated as follows; self-etch-control group: G-Premio universal adhesive was used in self-etch mode, total-etch-control: G-Premio universal adhesive was used in total-etch mode, self-etch-DMSO: Water-based DMSO (50% volume) was applied on the samples for 60 s followed by application of G-Premio universal adhesive in self-etch mode, and Total-etch-DMSO: The samples were etched, and then, water-based DMSO was applied on them for 60 s followed by the application of G-Premio universal adhesive in total-etch mode. Afterward, resin composite was placed on all samples and light-cured. The samples were kept in distilled water and subjected to 5000 thermal cycles. Microshear bond strength was measured using the universal testing machine and failure modes were analyzed using a stereomicroscope. Forty-eight human third molars were used for microleakage evaluation and a standardized class five cavity was prepared on the buccal surface of each tooth. The teeth were assigned into 4 groups and received aforementioned surface treatment and the cavities were filled with resin composite. After storing in water for 24 h, the samples were subjected to 5000 cycles of thermocycling and the microleakage level of the samples was evaluated using silver nitrate uptake at the bonded interface. Two-way ANOVA test was used to analyze the effect of bonding technique (self-etch/ total-etch) and DMSO pretreatment on the microshear bond strength and microleakage of G-Premio adhesive to dentin.

Results

Bonding technique had no effect on the bond strength values (p = 0.17) while DMSO pretreatment significantly decreased the microshear bond strength of the samples (p = 0.001). DMSO application increased microleakage significantly in total-etch (P-value = 0.02) while it had no effect in self-etch mode (P-value = 0.44).

Conclusions

Pretreatment of dentin using 50% DMSO significantly reduced the bond strength of G-Premio Bond in both self-etch and total-etch modes. DMSO effect on microleakage depended on the etching technique; DMSO increased the microleakage level when the adhesive was used in total-etch mode while did not affect the microleakage in self-etch mode.
The use of traditional medicine practitioner services for childhood illnesses among childbearing women: a multilevel analysis of demographic and health surveys in 32 sub-Saharan African countries
Authors: James Peter Bai , Gyasi Razak M. , Kasilo Ossy Muganga Julius , Wardle Jon , Bah Abdulai Jawo , Yendewa George A. , Mwaka Amos Deogratius
Published: April 2023

Background

Insights into the use of traditional medicine practitioners (TMP)-for common childhood diseases such as diarrhea and respiratory infections are important to understand the role of Traditional Medicine (TM) in reducing the increasing childhood morbidity and mortality in sub-Saharan Africa (SSA). However, a comprehensive picture of TMP utilisation and its associated factors for childhood illness in SSA is lacking. This study aimed to estimate the prevalence of the use of traditional medicine practitioner services to treat childhood illnesses among women with children under five years old and to identify individual and community-level factors associated with TMP use in SSA.

Methods

The analysis used Demographic and Health Surveys (DHS) dataset collected between 2010 and 2021 among 353,463 under-fives children from 32 SSA countries. Our outcome variable was the use of TMP for childhood illness, defined as having diarrhoea or fever/cough or both. Using STATA v14, we employed the random effect meta-analysis to estimate the pooled prevalence of TMP use for childhood illness and a two-level multivariable multilevel modelling to determine the individual and community-level factors associated with consultation of a TMP.

Results

Approximately [2.80% (95%CI: 1.88–3.90)] women who sought healthcare for childhood illnesses utilised the service of a TMP with the highest occurring in Cote d’Ivoire [16.3% (95%CI: 13.87–19.06)] and Guinea (13.80% (95%CI: 10.74–17.57)] but the lowest in Sierra Leone [0.10%(95%CI:0.01–1.61)]. Specifically, approximately [1.95% (95%CI: 1.33–2.68)] and [1.09% (95%CI:0.67–1.60)] of women sought the service of a TMP for childhood diarrhea and fever/cough, respectively. Women with no formal education [AOR = 1.62;95%CI:1.23–2.12], no media access [AOR = 1.19;95%CI:1.02–1.39), who lived in a male-headed household [AOR = 1.64;95%CI:1.27–2.11], without health insurance [AOR = 2.37;95%CI: 1.53–3.66], who considered it a problem getting permission to visit a health facility [AOR = 1.23;95%CI:1.03–1.47] and who perceived the size of their children at birth to be above average[AOR = 1.20;95%CI:1.03–1.41] had higher odds of using TMP for childhood illnesses.

Conclusions

Although the prevalence of TMP for childhood illnesses appeared low, our findings highlight that TMPs continue to play a critical role in managing childhood illnesses in SSA. It is essential that policymakers and service providers should incorporate the potential role of TMPs in the design, review and implementation of child health policies in SSA. Also, the interventions for curtailing childhood illnesses should be focused on the characteristics of women who use TMPs for childhood diseases identified in our study.
Can we optimize locations of hospitals by minimizing the number of patients at risk?
Authors: Fränti Pasi , Mariescu-Istodor Radu , Akram Awais , Satokangas Markku , Reissell Eeva
Published: April 2023

Background

To reduce risk of death in acute ST-segment elevation myocardial infraction (STEMI), patients must reach a percutaneous coronary intervention (PCI) within 120 min from the start of symptoms. Current hospital locations represent choices made long since and may not provide the best possibilities for optimal care of STEMI patients. Open questions are: (1) how the hospital locations could be better optimized to reduce the number of patients residing over 90 min from PCI capable hospitals, and (2) how this would affect other factors like average travel time.

Methods

We formulated the research question as a facility optimization problem, which was solved by clustering method using road network and efficient travel time estimation based on overhead graph. The method was implemented as an interactive web tool and tested using nationwide health care register data collected during 2015–2018 in Finland.

Results

The results show that the number of patients at risk for not receiving optimal care could theoretically be reduced significantly from 5 to 1%. However, this would be achieved at the cost of increasing average travel time from 35 to 49 min. By minimizing average travel time, the clustering would result in better locations leading to a slight decrease in travel time (34 min) with only 3% patients at risk.

Conclusions

The results showed that minimizing the number of patients at risk alone can significantly improve this single factor but, at the same time, increase the average burden of others. A more appropriate optimization should consider more factors. We also note that the hospitals serve also for other operators than STEMI patients. Although optimization of the entire health care system is a very complex optimization problems goal, it should be the aim of future research.
Integrating consumer perspectives into a large-scale health literacy audit of health information materials: learnings and next steps
Authors: Ayre Julie , Bonner Carissa , Gonzalez Jemma , Vaccaro Teresa , Cousins Michael , McCaffery Kirsten , Muscat Danielle M.
Published: April 2023

Background

Health information is less effective when it does not meet the health literacy needs of its consumers. For health organisations, assessing the appropriateness of their existing health information resources is a key step to addressing this issue. This study describes novel methods for a consumer-centred large-scale health literacy audit of existing resources and reflects on opportunities to further refine the method.

Methods

This audit focused on resources developed by NPS MedicineWise, an Australian not-for-profit that promotes safe and informed use of medicines. The audit comprised 4 stages, with consumers engaged at each stage: 1) Select a sample of resources for assessment; 2) Assess the sample using subjective (Patient Education Materials Assessment Tool) and objective (Sydney Health Literacy Lab Health Literacy Editor) assessment tools; 3) Review audit findings through workshops and identify priority areas for future work; 4) Reflect and gather feedback on the audit process via interviews.

Results

Of 147 resources, consumers selected 49 for detailed assessment that covered a range of health topics, health literacy skills, and formats, and which had varied web usage. Overall, 42 resources (85.7%) were assessed as easy to understand, but only 26 (53.1%) as easy to act on. A typical text was written at a grade 12 reading level and used the passive voice 6 times. About one in five words in a typical text were considered complex (19%). Workshops identified three key areas for action: make resources easier to understand and act on; consider the readers’ context, needs, and skills; and improve inclusiveness and representation. Interviews with workshop attendees highlighted that audit methods could be further improved by setting clear expectations about the project rationale, objectives, and consumer roles; providing consumers with a simpler subjective health literacy assessment tool, and addressing issues related to diverse representation.

Conclusions

This audit yielded valuable consumer-centred priorities for improving organisational health literacy with regards to updating a large existing database of health information resources. We also identified important opportunities to further refine the process. Study findings provide valuable practical insights that can inform organisational health actions for the upcoming Australian National Health Literacy Strategy.
A coordinated approach for managing polypharmacy among children with medical complexity: rationale and design of the Pediatric Medication Therapy Management (pMTM) randomized controlled trial
Authors: Orth Lucas E. , Feudtner Chris , Kempe Allison , Morris Megan A. , Colborn Kathryn L. , Gritz R. Mark , Linnebur Sunny A. , Begum Anowara , Feinstein James A.
Published: April 2023

Background

Children with medical complexity (CMC) often rely upon the use of multiple medications to sustain quality of life and control substantial symptom burden. Pediatric polypharmacy (≥ 5 concurrent medications) is prevalent and increases the risk of medication-related problems (MRPs). Although MRPs are associated with pediatric morbidity and healthcare utilization, polypharmacy is infrequently assessed during routine clinical care for CMC. The aim of this randomized controlled trial is to determine if a structured pharmacist-led Pediatric Medication Therapy Management (pMTM) intervention reduces MRP counts, as well as the secondary outcomes of symptom burden and acute healthcare utilization.

Methods

This is a hybrid type 2 randomized controlled trial assessing the effectiveness of pMTM compared to usual care in a large, patient-centered medical home for CMC. Eligible patients include all children ages 2–18 years old, with ≥ 1 complex chronic condition, and with ≥ 5 active medications, as well as their English-speaking primary caregivers. Child participants and their primary parental caregivers will be randomized to pMTM or usual care before a non-acute primary care visit and followed for 90 days. Using generalized linear models, the overall effectiveness of the intervention will be evaluated using total MRP counts at 90 days following pMTM intervention or usual care visit. Following attrition, a total of 296 CMC will contribute measurements at 90 days, which provides > 90% power to detect a clinically significant 1.0 reduction in total MRPs with an alpha level of 0.05. Secondary outcomes include Parent-Reported Outcomes of Symptoms (PRO-Sx) symptom burden scores and acute healthcare visit counts. Program replication costs will be assessed using time-driven activity-based scoring.

Discussion

This pMTM trial aims to test hypotheses that a patient-centered medication optimization intervention delivered by pediatric pharmacists will result in lower MRP counts, stable or improved symptom burdens, and fewer cumulative acute healthcare encounters at 90 days following pMTM compared to usual care. The results of this trial will be used to quantify medication-related outcomes, safety, and value for a high-utilization group of CMC, and outcomes may elucidate the role of integrated pharmacist services as a key component of outpatient complex care programs for this priority pediatric population.

Trial Registration

This trial was prospectively registered at clinicaltrials.gov (NCT05761847) on Feb 25, 2023.
Elevated expression of macrophage MERTK exhibits profibrotic effects and results in defective regulation of efferocytosis function in pulmonary fibrosis
Authors: She Yixin , Xu Xin , Yu Qingyang , Yang Xiangsheng , He Jianxing , Tang Xiao Xiao
Published: April 2023

Increased apoptosis of alveolar epithelial cells is a prominent feature of pulmonary fibrosis. Macrophage efferocytosis, phagocytosis of apoptotic cells by macrophages, is crucial for maintaining tissue homeostasis. Expression of Mer tyrosine kinase (MERTK, an important recognition receptor in efferocytosis) in macrophages is thought to be associated with fibrosis. However, how macrophage MERTK affects pulmonary fibrosis and whether it depends on efferocytosis are not yet clear. Here, we found elevated MERTK expression in lung macrophages from IPF patients and mice with bleomycin-induced pulmonary fibrosis. In vitro experiments showed that macrophages overexpressing MERTK exhibit profibrotic effects and that macrophage efferocytosis abrogates the profibrotic effect of MERTK by downregulating MERTK, forming a negative regulatory loop. In pulmonary fibrosis, this negative regulation is defective, and MERTK mainly exhibits profibrotic effects. Our study reveals a previously unsuspected profibrotic effect of elevated macrophage MERTK in pulmonary fibrosis and defective regulation of efferocytosis function as a result of that elevation, suggesting that targeting MERTK in macrophages may help to attenuate pulmonary fibrosis.
Redox-driven cardioprotective effects of sodium-glucose co-transporter-2 inhibitors: comparative review
Authors: Hoehlschen Julia , Hofreither Dominik , Tomin Tamara , Birner-Gruenberger Ruth
Published: April 2023

Sodium-glucose co-transporter-2 inhibitors are used in the treatment of diabetes but are also emerging as cardioprotective agents in heart diseases even in the absence of type 2 diabetes. In this paper, upon providing a short overview of common pathophysiological features of diabetes, we review the clinically reported cardio- and nephroprotective potential of sodium-glucose co-transporter-2 inhibitors currently available on the market, including Dapagliflozin, Canagliflozin, and Empagliflozin. To that end, we summarize findings of clinical trials that have initially drawn attention to the drugs’ organ-protective potential, before providing an overview of their proposed mechanism of action. Since we particularly expect that their antioxidative properties will broaden the application of gliflozins from therapeutic to preventive care, special emphasis was put on this aspect.
Association of abdominal adiposity, hepatic shear stiffness with subclinical left-ventricular remodeling evaluated by magnetic resonance in adults free of overt cardiovascular diseases: a prospective study
Authors: Qu Yali , Liu Jing , Li Jing , Shen Sumin , Chen Xiaoyi , Tang Hehan , Yuan Yuan , Xia Chunchao , Deng Liping , Chen Guoyong , Zheng Tianying , Chen Jie , Nie Lisha , Yuan Fang , Tong Nanwei , Peng Liqing , Song Bin
Published: April 2023

Background

Abdominal ectopic fat deposition and excess visceral fat depots in obesity may be related to cardiovascular disease (CVD) as both are involved in the metabolic syndrome (MetS). The awareness of the link between abdominal adiposity and subclinical cardiac remodeling would help improve treatment and outcome. Besides, liver fibrosis has also shown a potential relationship with cardiac dysfunction. Thus, we aimed to investigate the associations of magnetic resonance (MR)-based abdominal adiposity and hepatic shear stiffness with subclinical left ventricular (LV) remodeling while taking account of MetS-related confounders in adults free of overt CVD.

Methods

This was an exploratory, prospective study of 88 adults (46 subjects with obesity, 42 healthy controls) who underwent 3 T cardiac and body MR exams. Measures of abdominal MR included hepatic and pancreatic proton density fat fraction (H-PDFF and P-PDFF), hepatic shear stiffness by MR elastography, and subcutaneous and visceral adipose tissue (SAT and VAT). Cardiac measures included epicardial adipose tissue (EAT) and parameters of LV geometry and function. Associations were assessed using Pearson correlation and multivariable linear regression analyses, in which age, sex, and MetS-related confounders were adjusted for.

Results

The LV ejection fractions of all participants were within the normal range. Higher H-PDFF, P-PDFF, SAT and VAT were independently associated with lower LV global myocardial strain parameters (radial, circumferential and longitudinal peak strain [PS], longitudinal peak systolic strain rate and diastolic strain rate) (β = − 0.001 to − 0.41, p < 0.05), and P-PDFF, SAT and VAT were independently and positively associated with LV end-diastolic volume and stroke volume (β = 0.09 to 3.08, p ≤ 0.02) in the over-all cohort. In the obesity subgroup, higher P-PDFF and VAT were independently associated with lower circumferential and longitudinal PS, respectively (β = − 0.29 to − 0.05, p ≤ 0.01). No independent correlation between hepatic shear stiffness and EAT or LV remodeling was found (all p ≥ 0.05).

Conclusions

Ectopic fat depositions in the liver and pancreas, and excess abdominal adipose tissue pose a risk of subclinical LV remodeling beyond MetS-related CVD risk factors in adults without overt CVD. VAT may play a more considerable role as a risk factor for subclinical LV dysfunction than does SAT in individuals with obesity. The underlying mechanisms of these associations and their longitudinal clinical implications need further investigation.
Development of high cell density Limosilactobacillus reuteri KUB-AC5 for cell factory using oxidative stress reduction approach
Authors: Watthanasakphuban Nisit , Srila Pimsiriya , Pinmanee Phitsanu , Sompinit Kamonwan , Rattanaporn Kittipong , Peterbauer Clemens
Published: April 2023

Background

Expression systems for lactic acid bacteria have been developed for metabolic engineering applications as well as for food-grade recombinant protein production. But the industrial applications of lactic acid bacteria as cell factories have been limited due to low biomass formation resulted in low efficiency of biomanufacturing process. Limosilactobacillus reuteri KUB-AC5 is a safe probiotic lactic acid bacterium that has been proven as a gut health enhancer, which could be developed as a mucosal delivery vehicle for vaccines or therapeutic proteins, or as expression host for cell factory applications. Similar to many lactic acid bacteria, its oxygen sensitivity is a key factor that limits cell growth and causes low biomass production. The aim of this study is to overcome the oxidative stress in L. reuteri KUB-AC5. Several genes involved in oxidative and anti-oxidative stress were investigated, and strain improvement for higher cell densities despite oxidative stress was performed using genetic engineering.

Results

An in-silico study showed that L. reuteri KUB-AC5 genome possesses an incomplete respiratory chain lacking four menaquinone biosynthesis genes as well as a complete biosynthesis pathway for the production of the precursor. The presence of an oxygen consuming enzyme, NADH oxidase (Nox), leads to high ROS formation in aerobic cultivation, resulting in strong growth reduction to approximately 25% compared to anaerobic cultivation. Recombinant strains expressing the ROS scavenging enzymes Mn-catalase and Mn-superoxide dismutase were successfully constructed using the pSIP expression system. The Mn-catalase and Mn-SOD-expressing strains produced activities of 873 U/ml and 1213 U/ml and could minimize the ROS formation in the cell, resulting in fourfold and sevenfold higher biomass formation, respectively.

Conclusions

Expression of Mn-catalase and Mn-SOD in L. reuteri KUB-AC5 successfully reduced oxidative stress and enhanced growth. This finding could be applied for other lactic acid bacteria that are subject to oxidative stress and will be beneficial for applications of lactic acid bacteria for cell factory applications.
Metabolically versatile psychrotolerant Antarctic bacterium Pseudomonas sp. ANT_H12B is an efficient producer of siderophores and accompanying metabolites (SAM) useful for agricultural purposes
Authors: Musialowski M. , Kowalewska Ł. , Stasiuk R. , Krucoń T. , Debiec-Andrzejewska K.
Published: April 2023

Background

Bacterial siderophores are chelating compounds with the potential of application in agriculture, due to their plant growth-promoting (PGP) properties, however, high production and purification costs are limiting factors for their wider application. Cost-efficiency of the production could be increased by omitting purification processes, especially since siderophores accompanying metabolites (SAM) often also possess PGP traits. In this study, the metabolism versatility of Pseudomonas sp. ANT_H12B was used for the optimization of siderophores production and the potential of these metabolites and SAM was characterized in the context of PGP properties.

Results

The metabolic diversity of ANT_H12B was examined through genomic analysis and phenotype microarrays. The strain was found to be able to use numerous C, N, P, and S sources, which allowed for the design of novel media suitable for efficient production of siderophores in the form of pyoverdine (223.50–512.60 μM). Moreover, depending on the culture medium, the pH of the siderophores and SAM solutions varied from acidic (pH < 5) to alkaline (pH > 8). In a germination test, siderophores and SAM were shown to have a positive effect on plants, with a significant increase in germination percentage observed in beetroot, pea, and tobacco. The PGP potential of SAM was further elucidated through GC/MS analysis, which revealed other compounds with PGP potential, such as indolic acetic acids, organic acids, fatty acids, sugars and alcohols. These compounds not only improved seed germination but could also potentially be beneficial for plant fitness and soil quality.

Conclusions

Pseudomonas sp. ANT_H12B was presented as an efficient producer of siderophores and SAM which exhibit PGP potential. It was also shown that omitting downstream processes could not only limit the costs of siderophores production but also improve their agricultural potential.
Machine learning application for classification of Alzheimer's disease stages using 18F-flortaucipir positron emission tomography
Authors: Park Sang Won , Yeo Na Young , Lee Jinsu , Lee Suk-Hee , Byun Junghyun , Park Dong Young , Yum Sujin , Kim Jung-Kyeom , Byeon Gihwan , Kim Yeshin , Jang Jae-Won ,   for the Alzheimer’s Disease Neuroimaging Initiative
Published: April 2023

Background

The progression of Alzheimer’s dementia (AD) can be classified into three stages: cognitive unimpairment (CU), mild cognitive impairment (MCI), and AD. The purpose of this study was to implement a machine learning (ML) framework for AD stage classification using the standard uptake value ratio (SUVR) extracted from 18F-flortaucipir positron emission tomography (PET) images. We demonstrate the utility of tau SUVR for AD stage classification. We used clinical variables (age, sex, education, mini-mental state examination scores) and SUVR extracted from PET images scanned at baseline. Four types of ML frameworks, such as logistic regression, support vector machine (SVM), extreme gradient boosting, and multilayer perceptron (MLP), were used and explained by Shapley Additive Explanations (SHAP) to classify the AD stage.

Results

Of a total of 199 participants, 74, 69, and 56 patients were in the CU, MCI, and AD groups, respectively; their mean age was 71.5 years, and 106 (53.3%) were men. In the classification between CU and AD, the effect of clinical and tau SUVR was high in all classification tasks and all models had a mean area under the receiver operating characteristic curve (AUC) > 0.96. In the classification between MCI and AD, the independent effect of tau SUVR in SVM had an AUC of 0.88 (p < 0.05), which was the highest compared to other models. In the classification between MCI and CU, the AUC of each classification model was higher with tau SUVR variables than with clinical variables independently, which yielded an AUC of 0.75(p < 0.05) in MLP, which was the highest. As an explanation by SHAP for the classification between MCI and CU, and AD and CU, the amygdala and entorhinal cortex greatly affected the classification results. In the classification between MCI and AD, the para-hippocampal and temporal cortex affected model performance. Especially entorhinal cortex and amygdala showed a higher effect on model performance than all clinical variables in the classification between MCI and CU.

Conclusions

The independent effect of tau deposition indicates that it is an effective biomarker in classifying CU and MCI into clinical stages using MLP. It is also very effective in classifying AD stages using SVM with clinical information that can be easily obtained at clinical screening.
Emergence and clonal dissemination of KPC-3-producing Pseudomonas aeruginosa in China with an IncP-2 megaplasmid
Authors: Ge Haoyu , Qiao Jie , Zheng Jiahao , Xu Hao , Liu Ruishan , Zhao Junhui , Chen Ruyan , Li Chenyu , Guo Xiaobing , Zheng Beiwen
Published: April 2023

Background

Despite the global prevalence of Klebsiella pneumoniae Carbapenemase (KPC)-type class A β-lactamases, occurrences of KPC-3-producing isolates in China remain infrequent. This study aims to explore the emergence, antibiotic resistance profiles, and plasmid characteristics of blaKPC-3-carrying Pseudomonas aeruginosa.

Methods

Species identification was performed by MALDI-TOF-MS, and antimicrobial resistance genes (ARGs) were identified by polymerase chain reaction (PCR). The characteristics of the target strain were detected by whole-genome sequencing (WGS) and antimicrobial susceptibility testing (AST). Plasmids were analyzed by S1-nuclease pulsed-field gel electrophoresis(S1-PFGE), Southern blotting and transconjugation experiment.

Results

Five P. aeruginosa strains carrying blaKPC-3 were isolated from two Chinese patients without a history of travelling to endemic areas. All strains belonged to the novel sequence type ST1076. The blaKPC-3 was carried on a 395-kb IncP-2 megaplasmid with a conserved structure (IS6100-ISKpn27-blaKPC-3-ISKpn6-korC-klcA), and this genetic sequence was identical to many plasmid-encoded KPC of Pseudomonas species. By further analyzing the genetic context, it was supposed that the original of blaKPC-3 in our work was a series of mutation of blaKPC-2.

Conclusions

The emergence of a multidrug resistance IncP-2 megaplasmid and clonal transmission of blaKPC-3-producing P. aeruginosa in China underlined the crucial need for continuous monitoring of blaKPC-3 for prevention and control of its further dissemination in China.