bluuebunny/crossref_metadata_2025 huggingface dataset:
Vasohibin inhibition improves myocardial relaxation in a rat model of heart failure with preserved ejection fraction
Authors: Eaton Deborah M. , Lee Benjamin W. , Caporizzo Matthew A. , Iyengar Amit , Chen Christina Y. , Uchida Keita , Marcellin Guillaume , Lannay Yoann , Vite Alexia , Bedi Kenneth C. , Brady Claire F. , Smolyak Julia N. , Meldrum Danika , Dominic Jessica , Weingarten Noah , Patel Mrinal , Belec Andrew , Hached Khaled , Atluri Pavan , Van Der Laan Siem , Prosser Benjamin L. , Margulies Kenneth B.
Published: July 2024

Heart failure with preserved ejection fraction (HFpEF) is a complex syndrome associated with increased myocardial stiffness and cardiac filling abnormalities. Prior studies implicated increased α-tubulin detyrosination, which is catalyzed by the vasohibin enzymes, as a contributor to increased stabilization of the cardiomyocyte microtubule network (MTN) and stiffness in failing human hearts. We explored whether increased MTN detyrosination contributed to impaired diastolic function in the ZSF1 obese rat model of HFpEF and designed a small-molecule vasohibin inhibitor to ablate MTN detyrosination in vivo. Compared with ZSF1 lean and Wistar Kyoto rats, obese rats exhibited increased tubulin detyrosination concomitant with diastolic dysfunction, left atrial enlargement, and cardiac hypertrophy with a preserved left ventricle ejection fraction, consistent with an HFpEF phenotype. Ex vivo myocardial phenotyping assessed cardiomyocyte mechanics and contractility. Vasohibin inhibitor treatment of isolated cardiomyocytes from obese rats resulted in reduced stiffness and faster relaxation. Acute in vivo treatment with vasohibin inhibitor improved diastolic relaxation in ZSF1 obese rats compared with ZSF1 lean and Wistar Kyoto rats. Vasohibin inhibition also improved relaxation in isolated human cardiomyocytes from both failing and nonfailing hearts. Our data suggest the therapeutic potential for vasohibin inhibition to reduce myocardial stiffness and improve relaxation in HFpEF.
Influence of the initial microbiota on eggplant
shibazuke
pickle and eggplant juice fermentation
Authors: Sawada Kazunori , Yamada Takuji
Published: July 2024

The present study aimed to investigate the effects of the initial microbiota on microbial succession and metabolite transition during eggplant fermentation. Samples of traditional Japanese eggplant pickles,
shibazuke
, which were spontaneously fermented by plant-associated microbiota, were used for the analysis. Microbiota analysis indicated two successional patterns: early dominance of lactic acid bacteria superseded by aerobic bacteria and early dominance of lactic acid bacteria maintained to the end of the production process. Next,
shibazuke
production was modeled using filter-sterilized eggplant juice, fermenting the average composition of the initial
shibazuke
microbiota, which was artificially constructed from six major species identified during
shibazuke
production. In contrast to
shibazuke
production, all batches of eggplant juice fermentation showed almost identical microbial succession and complete dominance of
Lactiplantibacillus plantarum
in the final microbiota. These findings revealed the fate of initial microbiota under
shibazuke
production conditions: the early dominance of lactic acid bacteria that was maintained throughout, with
L. plantarum
ultimately predominating the microbiota. Furthermore, a comparison of the results between
shibazuke
production and eggplant juice fermentation suggested that
L. plantarum
is involved in the production of lactic acid, alanine, and glutamic acid during eggplant fermentation regardless of the final microbiota.

IMPORTANCE

The findings shown in this study provide insight into the microbial succession during spontaneous pickle fermentation and the role of
Lactiplantibacillus
plantarum in eggplant pickle production. Moreover, the novel method of using filter-sterilized vegetable juice with an artificial microbiota to emulate spontaneous fermentation can be applied to other spontaneously fermented products. This approach allows for the evaluation of the effect of specific initial microbiota in the absence of plant-associated bacteria from raw materials potentially promoting a greater understanding of microbial behavior in complex microbial ecosystems during vegetable fermentation.
Spatial–temporal variations in Mesozoic crustal thickness along the northeast Asian continental margin: Response to the subduction history of the Paleo-Pacific Plate
Authors: Tang Jie , Guo Peng , Wang Feng , Wang Yi-Ni , Xu Wen-Liang
Published: July 2024

The initial timing and history of subduction of the Paleo-Pacific Plate beneath Eurasia are controversial. The crustal thickness variations at a convergent margin typically reflect the convergent process between the two plates. This study used a recently proposed machine-learning model to estimate the crustal thickness variations along the northeast Asian continental margin during the Mesozoic. The northeast Asian continental margin, particularly the eastern North China Craton, had its thickest crust during the Early Triassic and underwent crustal thinning during the Middle–Late Triassic. The former reflects the subduction and collision between the South China Block and North China Craton, and the latter occurred in a post-orogenic extensional setting. From the Early to Middle Jurassic, sustained crustal thickening occurred along the northeast Asian continental margin, which coincided with initial subduction of the Paleo-Pacific Plate beneath Eurasia. From the Early to Late Cretaceous, the northeast Asian continental margin generally underwent crustal thinning, but crustal thickening events occurred at 130 Ma, 110 Ma, and 90 Ma, which is consistent with rollback of the subducted Paleo-Pacific Plate beneath Eurasia. The relationship between crustal thickness and mineralization suggests that thicker crust favored the formation of porphyry-type Cu-Mo deposits, whereas thinner crust in an extensional setting favored the formation of epithermal Au deposits related to magmatism.
Clofazimine pulmonary crystal deposition syndrome: a case of pseudo haemoptysis
Authors: Rechal Rinoosha , Prasad Virender Pratibh , Shah Milap , Maturu Venkata Nagarjuna
Published: July 2024

Clofazimine is an antimycobacterial, anti-inflammatory agent used in the management of leprosy and multidrug-resistant (MDR) tuberculosis. It has high oral bioavailability and poor solubility because of which prolonged administration of the drug results in its accumulation as intracellular biocrystals in tissue macrophages. We describe the case of a female patient in her early 30s who was on therapy for MDR tuberculosis. She presented with streaky haemoptysis of 6 months. Radiographic examination showed no abnormality in pulmonary vasculature and parenchyma. Bronchoscopy showed diffuse red-coloured flecks in tracheal and bronchial mucosa. The retrieved bronchoalveolar lavage (BAL) fluid was reddish-purple in colour. Microscopic examination of BAL fluid showed reddish clofazimine crystal deposition in alveolar macrophages. Serum and BAL clofazimine levels were performed using high performance liquid chromatography which confirmed high drug levels. She developed reddish discolouration of the skin during therapy due to clofazimine deposition. A diagnosis of pulmonary clofazimine crystal deposition syndrome causing pseudohaemoptysis was established.
Environmental Determinants of Islet Autoimmunity (ENDIA) longitudinal prospective pregnancy to childhood cohort study of Australian children at risk of type 1 diabetes: parental demographics and birth information
Authors: Thomson Rebecca L , Oakey Helena , Haynes Aveni , Craig Maria E , Harrison Leonard C , Wentworth John M , Anderson Amanda , Ashwood Pat , Barry Simon , Brittain Bek , Brown James D , Colman Peter G , Davis Elizabeth A , Hamilton-Williams Emma , Huynh Dao , Huynh Tony , Kim Ki-Wook , McGorm Kelly J , Morahan Grant , Rawlinson William , Sinnott Richard O , Soldatos Georgia , Tye-Din Jason A , Vuillermin Peter J , Penno Megan A S , Couper Jennifer J
Published: July 2024

Introduction

The Environmental Determinants of Islet Autoimmunity (ENDIA) Study is an ongoing Australian prospective cohort study investigating how modifiable prenatal and early-life exposures drive the development of islet autoimmunity and type 1 diabetes (T1D) in children. In this profile, we describe the cohort’s parental demographics, maternal and neonatal outcomes and human leukocyte antigen (HLA) genotypes.

Research design and methods

Inclusion criteria were an unborn child, or infant aged less than 6 months, with a first-degree relative (FDR) with T1D. The primary outcome was persistent islet autoimmunity, with children followed until a T1D diagnosis or 10 years of age. Demographic data were collected at enrollment. Lifestyle, clinical and anthropometric data were collected at each visit during pregnancy and clinical pregnancy and birth data were verified against medical case notes. Data were compared between mothers with and without T1D. HLA genotyping was performed on the ENDIA child and all available FDRs.

Results

The final cohort comprised 1473 infants born to 1214 gestational mothers across 1453 pregnancies, with 80% enrolled during pregnancy. The distribution of familial T1D probands was 62% maternal, 28% paternal and 11% sibling. The frequency of high-risk HLA genotypes was highest in T1D probands, followed by ENDIA infants, and lowest among unaffected family members. Mothers with T1D had higher rates of pregnancy complications and perinatal intervention, and larger babies of shorter gestation. Parent demographics were comparable to the Australian population for age, parity and obesity. A greater percentage of ENDIA parents were Australian born, lived in a major city and had higher socioeconomic advantage and education.

Conclusions

This comprehensive profile provides the context for understanding ENDIA’s scope, methodology, unique strengths and limitations. Now fully recruited, ENDIA will provide unique insights into the roles of early-life factors in the development of islet autoimmunity and T1D in the Australian environment.

Trial registration number

ACTRN12613000794707.
Surrogate measures of first-phase insulin secretion versus reference methods intravenous glucose tolerance test and hyperglycemic clamp: a systematic review and meta-analyses
Authors: Renklint Rebecka , Chninou Youssef , Heni Martin , Fritsche Andreas , Haering Hans-Ulrich , Wagner Robert , Otten Julia
Published: July 2024

Introduction

In this systematic review, we investigated the diagnostic accuracy of surrogate measures of insulin secretion based on fasting samples and the oral glucose tolerance test (OGTT). The first phase of insulin secretion was calculated using two gold standard methods; the hyperglycemic clamp (HGC) test and intravenous glucose tolerance test (IVGTT).

Research design and methods

We conducted searches in the PubMed, Cochrane Central, and Web of Science databases, the last of which was conducted at the end of June 2021. Studies were included that measured first-phase insulin secretion in adults using both a gold-standard reference method (either HGC or IVGTT) and one or more surrogate measures from either fasting samples, OGTT or a meal-tolerance test. QUADAS-2, a revised tool for the quality assessment of diagnostic accuracy studies, was used for quality assessment. Random-effects meta-analyses were performed to examine the correlation between first-phase measured with gold standard and surrogate methods.

Results

A total of 33 articles, encompassing 5362 individuals with normal glucose tolerance, pre-diabetes or type 2 diabetes, were included in our systematic review. Homeostatic model assessment (HOMA)-beta and Insulinogenic Index 30 (IGI(30)) were the surrogate measures validated in the largest number of studies (17 and 13, respectively). HOMA-beta’s pooled correlation to the reference methods was 0.48 (95% CI 0.40 to 0.56) The pooled correlation of IGI to the reference methods was 0.61 (95% CI 0.54 to 0.68). The surrogate measures with the highest correlation to the reference methods were Kadowaki (0.67 (95% CI 0.61 to 0.73)) and Stumvoll’s first-phase secretion (0.65 (95% CI 0.58 to 0.71)), both calculated from an OGTT.

Conclusions

Surrogate measures from the first 30 min of an OGTT capture the first phase of insulin secretion and are a good choice for epidemiological studies. HOMA-beta has a moderate correlation to the reference methods but is not a measure of the first phase specifically.

PROSPERO registration number

The meta-analysis was registered at PROSPERO (Id: CRD42020169064) before inclusion started.
Recruitment strategies and consent rates in a national prospective colorectal cancer screening cohort: results from year 1 of the Voyage Study
Authors: Yost Kathleen J , Carlson Rachel E , Kirt Christine R , Kirsch Emily J , Kneedler Bonny , Laffin Jennifer J , St Sauver Jennifer L , Finney Rutten Lila J , Grimm Jessica A , Olson Janet E
Published: July 2024

Objective

To identify the optimal incentive protocol for maximising participation while managing study costs during the Voyage trial.

Design

Prospective cohort (Voyage trial) of colorectal cancer (CRC) incidence and mortality outcomes in individuals screened with multitarget stool DNA (mt-sDNA) served as the population. A subset was randomised to receive postage stamps as a pre-consent incentive, or as a post-consent incentive after completion of the consent and questionnaire. Descriptive statistics from year 1 are reported.

Results

During year 1 of the Voyage trial, a total of 600 258 individuals with mt-sDNA orders received at Exact Sciences Laboratories were randomly selected and invited to participate. Of those, 26 429 (4.4%) opted in, 14 365 of whom (54.3%) consented. The opt-in and consent samples were similar to the target population with respect to sex but differed by geographic residence and age (p<0.001). For the embedded incentive experiment, 2333 were randomised to the pre-incentive arm, while 2342 were randomised to the post-incentive arm. Overall consent rate in the incentive trial was 56.4% (60.9% for the pre-consent incentive arm (1421/2333) vs 52.0% for the post-consent incentive arm (1217/2342), p<0.001). Cost reduction was observed for the pre-consent incentive group, and higher response rates were seen among older versus younger individuals.

Conclusions

Pre-consent incentive option was associated with a higher participation rate and lower costs and was used for the remainder of study recruitment. CRC incidence and mortality vary with age; thus, adjusting for differential participation by age and region will be important in analyses of Voyage data.

Trial registration number

NCT04124406.
Statin prescriptions and progression of advanced fibrosis risk in primary care patients with MASLD
Authors: Schreiner Andrew D , Zhang Jingwen , Petz Chelsey A , Moran William P , Koch David G , Marsden Justin , Bays Chloe , Mauldin Patrick D , Gebregziabher Mulugeta
Published: July 2024

Objective

We aimed to determine the association of statins with progression to a high risk for advanced fibrosis in primary care patients with metabolic dysfunction-associated steatotic liver disease (MASLD).

Design

This retrospective cohort study of electronic health record data included patients with MASLD and an initial low or indeterminate risk for advanced fibrosis, determined by Fibrosis-4 Index (FIB-4) score (<2.67). Patients were followed from the index FIB-4 until the primary outcome of a high-risk FIB-4 (≥2.67) or the end of the study period. Prescription for a statin during follow-up was the primary exposure. We developed Cox regression models for the time to a high-risk FIB-4 score with statin therapy as the primary covariate and adjusting for baseline fibrosis risk, demographic and comorbidity variables.

Results

The cohort of 1238 patients with MASLD was followed for a mean of 3.3 years, with 47% of patients receiving a prescription for a statin, and 18% of patients progressing to a high-risk FIB-4. In the adjusted Cox model with statin prescription as the primary exposure, statins were associated with a lower risk (HR 0.60; 95% CI 0.45 to 0.80) of progressing to a FIB-4≥2.67. In the adjusted Cox models with statin prescription intensity as the exposure, moderate (HR 0.60; 95% CI 0.42 to 0.84) and high intensity (HR 0.61; 95% CI 0.42 to 0.88) statins were associated with a lower risk of progressing to a high-risk FIB-4.

Conclusion

Statin prescriptions, and specifically moderate and high intensity statin prescriptions, demonstrate a protective association with fibrosis risk progression in primary care patients with MASLD.
Legislation for advancing women’s leadership in the health sector in India and Kenya: a ‘law cube’ approach to identify ways to strengthen legal environments for gender equality
Authors: Evagora-Campbell Mireille , Kedia Sapna , Odero Henry Owoko , Uppal Radhika , Odunga Sally Atieno , Mattoo Tusharika , Miranda Patricia Blardony , Tanaka Sonja , Kiwuwa-Muyingo Sylvia , Verma Ravi , Hawkes Sarah , Buse Kent
Published: July 2024

Objectives

This paper examines the availability of legal provisions, or the lack thereof, that support women to progress equitably into leadership positions within the health workforce in India and Kenya.

Methods

We adapted the World Bank’sWomen, Business and Lawframework of legal domains relevant to gender equality in the workplace and applied a ‘law cube’ to analyse the comprehensiveness, accountability and equity and human rights considerations of 27 relevant statutes in India and 11 in Kenya that apply to people in formal employment within the health sector. We assessed those laws against 30 research-validated good practice measures across five legal domains: (1) pay; (2) workplace protections; (3) pensions; (4) care, family life and work–life balance; and (5) reproductive rights. In India, the pension domain and related measures were not assessed because the pension laws do not apply to the public and private sector equally.

Results

Several legal domains are addressed inadequately or not at all, including pay in India, reproductive rights in Kenya and the care, family life and the work–life balance domain in both countries. Additionally, we found that among the Kenyan laws reviewed, few specify accountability mechanisms, and equity and human rights measures are mainly absent from the laws assessed in both countries. Our findings highlight inadequacies in the legal environments in India and Kenya may contribute to women’s under-representation in leadership in the health sector. The absence of specified accountability mechanisms may impact the effective implementation of legislation, undermining their potential to promote equal opportunities.

Conclusions

Government action is needed in both countries to ensure that legislation addresses best practice provisions, equity and human rights considerations, and provides for independent review mechanisms to ensure accountability for implementation of existing and future laws. This would contribute to ensuring that legal environments uphold the equality of opportunity necessary for realising gender justice in the workplace for the health workforce.

Primary source of funding

Bill & Melinda Gates Foundation (INV-031372).
Impact of the COVID-19 pandemic from the perspective of patients with cardiovascular disease in Australia: mixed-methods study
Authors: Trivedi Ritu , Jaure Allison , Chiang Jason , Thaliph Ayesha , Shaw Tim , Chow Clara K , Laranjo Liliana
Published: July 2024

Objectives

The study explored the perceived impacts of COVID-19 and its associated policies and social restrictions on health, self-management and access to healthcare.

Design

Cross-sectional observational (online survey) and qualitative study (semi-structured interviews and thematic analysis).

Setting

Australia.

Participants

People with self-reported cardiovascular disease (CVD) and/or risk factors.

Results

Survey responses were collected from 690 participants (43.8% women, 40.1% over 65 years). Participants reported that their heart health had been affected by the pandemic (26.3%), were less likely to exercise (47.1%), have a healthy diet (25.9%) and take medications (9.4%). A large proportion were admitted to hospital (46.2%) and presented to the emergency department (40.6%). Difficulties in accessing healthcare providers (53.2%) and use of telemedicine (63.6%) were reported. We conducted 16 semi-structured interviews and identified five key themes: adding burden in seeking medical care, impediments in accessing a readjusted health system, exacerbating vulnerability and distress, coping with self-management and adapting to telehealth.

Conclusions

Patients with CVD expressed an additional burden in seeking medical care and difficulties navigating a readjusted health system during the COVID-19 pandemic. Associated policies and access issues heightened vulnerabilities and distress, making self-management of health difficult for patients with CVD.
Impact of free school lunch program on nutritional status and academic outcomes among school children in India: A systematic review
Authors: Raveenthiranathan Lakshana , Ramanarayanan Venkitachalam , Thankappan KR
Published: July 2024

Introduction

Mid-day meal programmes (MDM) were introduced in India to improve school attendance, nutritional status and educational outcomes of school children. Numerous primary studies have examined the impact of the MDM programmes on both nutritional and educational outcomes in various settings across the country. However, synthesising the findings from these studies has been challenging. To address this gap, we conducted a systematic review to assess the effects of MDM programmes on the nutritional and academic outcomes of school children in India.

Methods

A comprehensive literature search was conducted, and relevant studies published between 1997 and 2022 were included. Two reviewers independently conducted study selection, data extraction and risk of bias assessment. The results were synthesised descriptively.

Results

The systematic review included 31 studies. Among them, 16 studies focused on academic outcomes, while 18 studies reported children’s nutritional status. Studies on MDM Scheme (MDMS) in children show mixed results on nutritional outcomes. While some studies show marginal improvements in height and weight measurements, others show no significant improvement. Regular MDMS access improves enrollment, attendance and retention rates for children, with lower dropout rates and higher academic achievement. However, its impact on academic performance remains unclear.

Conclusion

The MDM programme in India was effective in improving the academic achievement and a few nutritional outcomes of school children, underscoring the importance of sustaining MDM programmes in India.

Protocol registration number

The review was prospectively registered in PROSPERO (CRD42023391776). Available from:https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023391776.
Biomarker of severity in hospitalised patients with COVID-19: a retrospective study
Authors: Qian Fen-Hong , Liu Yu-Xue , Cao Yu , Huang Jing , Zhu Rong-Hao
Published: July 2024

Background

The novel COVID-19 was rapidly spreading and was highly contagious. COVID-19 caused over 6 million deaths worldwide, with high mortality rates, particularly in severe cases.

Objective

This study aimed to investigate whether serum albumin-neutrophil count to lymphocyte count ratio (NLR) score (ANS) could be used as a prognostic indicator of COVID-19 severity.

Design

A retrospective study.

Participants

Based on the WHO diagnostic criteria, patients were classified as either non-severe (n=270) or severe (n=100).

Primary and secondary outcome measures

NLR, serum albumin level and ANS.

Main results

The NLR of patients with severe disease was significantly higher than that of those with non-severe disease. Serum albumin levels were significantly lower in patients with severe disease than in those with non-severe disease. The cut-off values representing the maximum potential effectiveness of serum albumin and NLR were 33.5 g/L and 8.25, respectively, according to the Youden index. In patients with severe COVID-19, we observed that the serum albumin level, NLR and ANS were independent prognostic indicators of severe COVID-19 using logistic analysis. The relative risk of severe COVID-19 was 7.65 (95% CI 3.72 to 15.75, p<0.05) in the ANS 2 group compared with that in ANS 0.

Conclusions

ANS could be used as a prognostic indicator of COVID-19 severity.
Multimethods study to develop tools for competency-based assessments of implementation research training programmes in low and middle-income countries
Authors: Alonge Olakunle , Rao Aditi , Kalbarczyk Anna , Ibisomi Latifat , Dako-Gyeke Phyllis , Mahendradhata Yodi , Rojas Carlos Alberto , Jacobs Choolwe , Torpey Kwasi , Gonzalez Marulanda Edwin Rolando , Launois Pascal , Vahedi Mahnaz
Published: July 2024

Introduction

Methods and validated tools for evaluating the performance of competency-based implementation research (IR) training programmes in low–middle-income countries (LMICs) are lacking. In this study, we developed tools for assessing the performance of IR training programmes based on a framework of IR core competencies in LMICs.

Methods

We developed self-assessment and objective-assessment tools drawing on the IR competency framework. We used exploratory factor analyses and a one-parameter logistic model to establish construct validity and internal consistency of the tools drawing on a survey conducted in 2020 with 166 trainees before and after an index IR course across five universities and LMICs under the Special Program for Research and Training in Tropical Diseases postgraduate IR training scheme. We conducted key informant interviews (KII) with 20 trainees and five trainers to reflect on the usefulness of the tools and framework for guiding IR training in LMICs.

Results

Two 16-item tools for self-assessment of IR knowledge and self-efficacy and a 40-item objective assessment tool were developed. The factor loadings of items in the self-assessment tools were 0.65–0.87 with Cronbach’s alpha (α) of 0.97, and 0.77–0.91 with α of 0.98 for the IR knowledge and self-efficacy tools, respectively. The distribution of item difficulty in the objective-assessment tool was consistent before and after the index IR course. Pearson correlation coefficient (r) between the self-assessed and objectively assessed IR knowledge before the index IR course was low, r=0.27 (p value: <0.01), with slight improvements after the index IR course, r=0.43 (p value: <0.01). All KII respondents reported the assessment tools and framework were valid for assessing IR competencies.

Conclusion

The IR competency framework and tools developed for assessing IR competencies and performance of IR training programmes in LMICs are reliable and valid. Self-assessment methods alone may not suffice to yield a valid assessment of performance in these settings.
Study protocol for a randomised, phase II, double-blind, experimental medicine study of obinutuzumab versus rituximab in ANCA-associated vasculitis: ObiVas
Authors: McGovern Dominic Paul , McClure Mark E , Coates Matthew , Bond Simon , Martinez Del Pero Marcos , Mynard Kim , Lee Jacinta , Smith Rona M , Jayne David R , Clatworthy Menna Ruth , Jones Rachel B
Published: July 2024

Introduction

Relapses in ANCA-associated vasculitis (AAV) increase the incidence of end-organ damage and their prevention requires prolonged immunosuppressive therapy. Rituximab, a type I anti-CD20 B cell depleting monoclonal antibody, is the current standard of care for induction of disease remission. Rituximab is not always effective and is associated with a high subsequent relapse risk. Obinutuzumab is a type II anti-CD20 humanised monoclonal antibody with the potential to obtain greater tissue B cell depletion than rituximab and reduce relapse risk in AAV.

Methods and analysis

ObiVas is a randomised, phase II, double-blind controlled trial that will compare the mechanistic effects of rituximab and obinutuzumab in the induction treatment of patients with AAV positive for proteinase 3 ANCA (PR3-ANCA). 26 patients, either newly diagnosed or relapsing, will be recruited from a single centre and randomised in a 1:1 ratio to receive 1000 mg rituximab or obinutuzumab as induction therapy on days 1 and 15, alongside a tapering glucocorticoid regimen. The primary end point is CD19+B cell depletion in nasal-associated lymphoid tissue (NALT), assessed as change from baseline to week 26. Secondary outcomes will compare the safety and clinical efficacy of rituximab and obinutuzumab and their impact on immune biomarkers, including tissue and peripheral blood lymphocyte subsets and PR3-ANCA binding levels. Patients are followed through to week 78. The trial opened for recruitment in January 2023 and is forecasted to complete recruitment by the end of 2024.

Ethics and dissemination

For all patients, informed written consent will be obtained in keeping with Good Clinical Practice. Trial results will be disseminated to the relevant scientific, clinical and patient communities on trial closure. NALT data analysis will start before trial completion. Other analyses will be reported after trial completion. This trial was given ethical approval by Edgbaston (West Midlands) Research Ethics Committee (approval reference 22/WM/0174).

Trial registration number

ISRCTN13069630.
Exploring subjective quality-of-life indicators in long-term care facilities: a mixed-methods research protocol
Authors: Nova Amanda A , Declercq Anja , Heckman George A , Hirdes John P , McAiney Carrie , De Lepeleire Jan
Published: July 2024

Introduction

Improving quality of life has become a priority in the long-term care (LTC) sector internationally. With development and implementation guidance, standardised quality-of-life monitoring tools based on valid, self-report surveys could be used more effectively to benefit LTC residents, families and organisations. This research will explore the potential for subjective quality-of-life indicators in the interRAI Self-Reported Quality of Life Survey for Long-Term Care Facilities (QoL-LTCF).

Methods and analysis

Guided by the Medical Research Council Framework, this research will entail a (1) modified Delphi study, (2) feasibility study and (3) realist synthesis. In study 1, we will evaluate the importance of statements and scales in the QoL-LTCF by administering Delphi surveys and focus groups to purposively recruited resident and family advisors, researchers, and LTC clinicians, staff, and leadership from international quality improvement organisations. In study 2, we will critically examine the feasibility and implications of risk-adjusting subjective quality-of-life indicators. Specifically, we will collect expert stakeholder perspectives with interviews and apply a risk-adjustment methodology to QoL-LTCF data. In study 3, we will iteratively review and synthesise literature, and consult with expert stakeholders to explore the implementation of quality-of-life indicators.

Ethics and dissemination

This study has received approval through a University of Waterloo Research Ethics Board and the Social and Societal Ethics Committee of KU Leuven. We will disseminate our findings in conferences, journal article publications and presentations for a variety of stakeholders.
Economic evaluation of Maternal Depression Treatment in HIV (M-DEPTH) for perinatal depression among women living with HIV in Uganda: a cost-effectiveness analysis
Authors: McBain Ryan , Okunogbe Adeyemi , Gwokyalya Violet , Wanyenze Rhoda K , Wagner Glenn
Published: July 2024

Objective

We conducted a cost-effectiveness analysis of an evidence-based collaborative care model for treatment of perinatal depression among women living with HIV in Uganda.

Design

Maternal Depression Treatment in HIV (M-DEPTH) is a cluster randomised controlled trial implemented from July 2019 to August 2023, during which 391 pregnant women with mild-to-severe depressive symptoms were randomised to receive stepped care for depression (M-DEPTH: behavioural and pharmacological treatments) or care as usual (CAU: hospital referral for severe cases), at one of eight public health facilities in Uganda.

Methods

We implemented time-driven, activity-based costing to determine the economic cost of M-DEPTH from a societal perspective, compared with CAU. Change in the prevalence of depressive disorder—from enrolment to 18 months postpartum—was quantified using the Patient Health Questionnaire, with depressive disorder assigned a disability weight according to the Global Burden of Disease project. Incremental cost-effectiveness ratios (ICERs) were expressed as cost per disability-adjusted life years (DALY) averted.

Results

The estimated economic cost of M-DEPTH was US$128.82 per participant, compared with $1.53 per participant for CAU. At baseline, prevalence of depressive disorder did not differ according to treatment assignment. Remission of depressive disorder was more prevalent among those assigned to M-DEPTH—across all time periods, including 18-month follow-up (aOR: 0.09; 95% CI 0.05 to 0.16; p<0.001). This yielded an ICER of $397 per DALY averted, when limiting benefits to those accrued over the study period. Sensitivity analyses generated estimates ranging from $162 to $418 per DALY averted.

Conclusions

M-DEPTH represents a financially feasible task-shifted model of evidence-based perinatal depression screening and treatment. The intervention is cost-effective at a willingness-to-pay threshold of less than half of median gross domestic product per capita in Uganda.

Trial registration number

NCT03892915.
Longitudinal cohort study of discrepancies between prescribed and administered polypharmacy rates: implications for National Aged Care Quality Indicator Programs
Authors: Wabe Nasir , Urwin Rachel , Seaman Karla , Westbrook Johanna I
Published: July 2024

Background

Polypharmacy is frequently used as a quality indicator for older adults in Residential Aged Care Facilities (RACFs) and is measured using a range of definitions. The impact of data source choice on polypharmacy rates and the implications for monitoring and benchmarking remain unclear. We aimed to determine polypharmacy rates (≥9 concurrent medicines) by using prescribed and administered data under various scenarios, leveraging electronic data from 30 RACFs.

Method

A longitudinal cohort study of 5662 residents in New South Wales, Australia. Both prescribed and administered polypharmacy rates were calculated biweekly from January 2019 to September 2022, providing 156 assessment times. 12 different polypharmacy rates were computed separately using prescribing and administration data and incorporating different combinations of items:
medicines and non-medicinal products
,
any medicines
and
regular medicines
across four scenarios: no, 1-week, 2-week and 4-week look-back periods. Generalised estimating equation models were employed to identify predictors of discrepancies between prescribed and administered polypharmacy.

Results

Polypharmacy rates among residents ranged from 33.9% using data on administered
regular medicines
with no look-back period to 63.5% using prescribed
medicines and non-medicinal products
with a 4-week look-back period. At each assessment time, the differences between prescribed and administered polypharmacy rates were consistently more than 10.0%, 4.5%, 3.5% and 3.0%, respectively, with no, 1-week, 2-week and 4-week look-back periods. Diabetic residents faced over two times the likelihood of polypharmacy discrepancies compared with counterparts, while dementia residents consistently showed reduced likelihood across all analyses.

Conclusion

We found notable discrepancies between polypharmacy rates for prescribed and administered medicines. We recommend a review of the guidance for calculating and interpreting polypharmacy for national quality indicator programmes to ensure consistent measurement and meaningful reporting.
Evening regular activity breaks extend subsequent free-living sleep time in healthy adults: a randomised crossover trial
Authors: Gale Jennifer T , Haszard Jillian J , Wei Dorothy L , Taylor Rachael W , Peddie Meredith C
Published: July 2024

Objective

To determine if performing regular 3-min bouts of resistance exercise spread over 4 hours in an evening will impact subsequent sleep quantity and quality, sedentary time and physical activity compared with prolonged uninterrupted sitting.

Methods

In this randomised crossover trial, participants each completed two 4-hour interventions commencing at approximately 17:00 hours: (1) prolonged sitting and (2) sitting interrupted with 3 min of bodyweight resistance exercise activity breaks every 30 min. On completion, participants returned to a free-living setting. This paper reports secondary outcomes relating to sleep quality and quantity, physical activity and sedentary time which were assessed using wrist-worn ActiGraph GT3+ accelerometers paired with a sleep and wear time diary.

Results

A total of 28 participants (women, n=20), age 25.6±5.6 years, body mass index 29.5±6.7 kg/m2(mean±SD) provided data for this analysis. Compared with prolonged sitting, regular activity breaks increased mean sleep period time and time spent asleep by 29.3 min (95% CI: 1.3 to 57.2, p=0.040) and 27.7 min (95% CI: 2.3 to 52.4, p=0.033), respectively, on the night of the intervention. There was no significant effect on mean sleep efficiency (mean: 0.2%, 95% CI: −2.0 to 2.4, p=0.857), wake after sleep onset (1.0 min, 95% CI: −9.6 to 11.7, p=0.849) and number of awakenings (0.8, 95% CI: −1.8 to 3.3, p=0.550). Subsequent 24-hour and 48-hour physical activity patterns were not significantly different.

Conclusions

Performing bodyweight resistance exercise activity breaks in the evening has the potential to improve sleep period and total sleep time and does not disrupt other aspects of sleep quality or subsequent 24-hour physical activity. Future research should explore the longer-term impact of evening activity breaks on sleep.

Trial registration number

Australian New Zealand Clinical Trials Registry (ACTRN12621000250831).
Exploring the interplay of interpersonal and contextual dynamics in youth sports injuries: a comprehensive narrative review
Authors: Bjørndal Christian Thue , Hausken-Sutter Solveig , Møller Merete , Myklebust Grethe , Grindem Hege
Published: July 2024

Injuries are recognised in sports and exercise medicine as not isolated incidents but complex outcomes. This is because an athlete’s health trajectory is understood to be shaped by dynamic, complex linkages between individual performance, biology, and the wider social and cultural contexts and systems in which individuals perform. Despite this recognition, little attention has been paid to how interpersonal and contextual dynamics can potentially affect the risk of injury by influencing the choices and decisions made by coaches, parents and athletes. To address this gap, this narrative review bridges insights from sociocultural studies in sports with the findings of sports injury research. The narrative review aims to identify and summarise how interpersonal and contextual dynamics influence the risk of youth sports injuries. The results reveal the pressures faced by athletes, often leading to compromised health. Moreover, the review underscores the importance of designing complex interventions and strategies to promote healthier practices in youth sports. Specifically, intervention programmes should prioritise raising awareness of injury risks, cultivating effective communication skills and fostering supportive training environments.
Investigating the association between intralimb strength ratio, interlimb strength and range of motion asymmetry index, and functional limitations with fall incidence among older adults: protocol for a prospective cohort study
Authors: Nasiri Zahra , Letafatkar Amir , Hosseinzadeh Mahdi
Published: July 2024

The present study aims to identify the intralimb strength ratio, interlimb strength and range of motion asymmetry index in elderly individuals and then investigate the association between these asymmetry indices and functional limitations among older adults. 200 eligible elderly individuals will participate in this study. Muscle strength and range of motion will be assessed for eight lower limb muscle groups. The asymmetry of muscle strength and range of motion will be calculated. The variables of functional limitations, for example, falling, walking, static balance and dynamic balance status, will be evaluated. The significance of risk factors for fall incidence and functional limitations will be investigated using the multiple linear regression analysis, which will create a separate model with each of the strength and range of motion asymmetries variables. Predictive performance of strength and range of motion asymmetries for fall incidence and functional limitations will be conducted by the corresponding receiver-operating curve to define a cut-off for strength and range of motion asymmetries. This prospective cohort will provide important data on interlimb strength and range of motion asymmetry with functional limitation and fall incidence in elderlies. If successful, the potential benefits from reducing between-limb asymmetry in selected muscle strength or range of motion will be of high interest to the professionals and researchers who work with elderly adults. Finally, the holistic picture of the imbalances/asymmetries this cohort provides will potentially have implications for improving functional capacity and reducing fall incidence in the elderly population.
Oncological outcomes after laparotomic, laparoscopic, and robot-assisted laparoscopic staging for early-stage high–intermediate or high-risk endometrial cancer
Authors: Koek Ruben C G , Wenzel Hans , Jonges Geertruida N , Lok Christianne A R , Zweemer Ronald , Gerestein Cornelis G
Published: July 2024

Objectives

To compare oncological outcomes in patients with early-stage high–intermediate or high-risk endometrial cancer undergoing surgical staging by laparotomy, conventional laparoscopy, or robot-assisted laparoscopy.

Methods

Patients diagnosed between 2015 and 2021 with stage I–II (International Federation of Gynecology and Obstetrics 2009), high–intermediate or high-risk endometrial cancer who underwent staging surgery, were identified in the Netherlands Cancer Registry. Five-year disease-free survival and overall survival were calculated using the Kaplan-Meier method, and differences between groups were evaluated using log-rank testing. Additionally, survival analyses were stratified by histological subtype. The effect of surgical modality on risk of recurrence and all-cause death was assessed by performing Cox regression analysis with inverse probability treatment weighting.

Results

In total 941 patients met the inclusion criteria, of whom 399 (42.4%) underwent staging surgery by laparotomy, 273 (29.0%) by laparoscopy, and 269 (28.6%) by robot-assisted laparoscopy. Baseline characteristics were comparable between the three groups. No difference in disease-free survival (75.0% vs 71.2% vs 79.0% p=0.35) or overall survival (72.7% vs 72.3% vs 71.2% p=0.98) was observed between patients after laparotomy, laparoscopy, or robot-assisted laparoscopy, respectively. Subanalyses based on histological subtype showed comparable disease-free survival and overall survival between surgical approaches. After correcting for possible confounders by means of inverse probability treatment weighting, there was no significantly increased risk of recurrence or risk of all-cause death after laparoscopy or robot-assisted laparoscopy.

Conclusion

Laparoscopic and robot-assisted laparoscopic staging surgery in women with early-stage high–intermediate or high-risk endometrial cancer are safe alternatives to laparotomic staging surgery.
ihtObtura: A novel liquid embolic agent with post-embolization radiopacity loss, in endovascular treatment of brain arteriovenous malformations, dural arteriovenous fistulas, and tumors: CLARIDAD trial
Authors: Llibre-Guerra Juan Carlos , Guimaraens Leopoldo , Kadziolka Krzysztof Bartosz , Siddiqui Adnan H , Chapot René , Gil Alberto
Published: July 2024

Background

Endovascular embolization is frequently used for vascular lesions of the head and neck. Newer agents may help to enhance visualization and improve treatment outcomes.

Methods

The CLARIDAD clinical trial was a prospective, single center, first-in-man investigation of neurovascular embolization using the novel embolic agentihtObtura for a broad indication, covering the need for a liquid embolic agent in head and neck procedures. The primary outcomes assessed were therapeutic efficacy to deliverihtObtura to embolize the catheterized pedicle and associated angiographic vascularity, and subsequent loss of radiopacity. Safety endpoints included procedural adverse events, modified Rankin Scale (mRS) score, morbidity, and mortality. Radiologic and clinical follow-up evaluations were conducted at 30, 90, 180 days, and 1 year post-treatment.

Results

65 consecutive patients (mean age 37.8 years, 50.8% women) were treated over 129 sessions. A total of 42 brain arteriovenous malformations (AVMs; 90% grades III and IV), 8 dural arteriovenous fistulas (DAVFs), and 15 hypervascular tumors were treated withihtObtura using an average of 3.9 mL per session and 7.7 mL per patient. We achieved therapeutic effectiveness in 99% of catheterizations. Radiopacity loss was complete after 74.3% of the sessions at 30 days, 95.6% at 90 days, and 100% at the 1 year follow-up. Serious adverse events (mRS score >2) occurred in two patients (3.1%) with previously ruptured high grade AVMs leading to one death and one permanent disabling morbidity.

Conclusions

The study showed thatihtObtura was a novel, safe, and effective liquid embolic agent for the treatment of AVMs, DAVFs, and hypervascular tumors. Its key property of significant radiopacity loss contributes to improve anatomical understanding, particularly in staged procedures, as well as reduction in post-procedural imaging artifact. There may be additional benefits of eliminating tantalum from the embolic mixture in terms of lesion penetration.
Structure Prompt Augmented Language Model Embedding on Electrical Equipment Defect Knowledge Graph
Authors: Yang Hong , Meng Xiaokai , Yu Hua , Bai Yang , Han Yu , Liu Yongxin
Published: July 2024

Knowledge graphs have demonstrated significant impact in the power grid domain, facilitating various applications such as defect diagnosis and grid management. However, their reasoning capabilities have not been fully exploited. In this paper, we explore the utilization of knowledge graphs for power grid defect diagnosis. We construct an electrical equipment defect knowledge graph and predict missing links, which is also known as Knowledge Graph Completion (KGC). However, we notice the long-tail problem in electrical equipment knowledge graph. To tackle this challenge, we propose a novel text-based model named SPALME (Structure Prompt Augmented Language Model Embedding) that incorporates structural information as prompts. Our model leverages the power of pre-trained language models, allowing it to comprehend the semantic information of entities and relationships in the knowledge graph. Additionally, by integrating structural information as prompts during the learning process, our model gains a deeper understanding of the graph’s topological structure efficiently, effectively capturing intricate dependencies between grid equipments. We evaluate our approach on various datasets. The results demonstrate that our model consistently outperforms baseline methods on the majority of the datasets.