bluuebunny/crossref_metadata_2025_split huggingface dataset:
Using the Delphi process to determine the minimum clinically important effect size for the Balanced-2 randomised controlled trial
Authors: Deng Carolyn , Sidebotham David 
Published: May 2023

Background: The sample size calculation is an important step in designing randomised controlled trials. For a trial comparing a control and an intervention group, where the outcome is binary, the sample size calculation requires choosing values for the anticipated event rates in both the control and intervention groups (the effect size), and the error rates. The Difference ELicitation in TriAls guidance recommends that the effect size should be both realistic, and clinically important to stakeholder groups. Overestimating the effect size leads to sample sizes that are too small to reliably detect the true population effect size, which in turn results in low achieved power. In this study, we use the Delphi approach to gain consensus on what the minimum clinically important effect size is for Balanced-2, a randomised controlled trial comparing processed electroencephalogram-guided ‘light’ to ‘deep’ general anaesthesia on the incidence of postoperative delirium in older adults undergoing major surgery. Methods: Delphi rounds were conducted using electronic surveys. Surveys were administered to two stakeholder groups: specialist anaesthetists from a general adult department in Auckland City Hospital, New Zealand (Group 1), and specialist anaesthetists with expertise in clinical research, identified from the Australian and New Zealand College of Anaesthetist’s Clinical Trials Network (Group 2). A total of 187 anaesthetists were invited to participate (81 from Group 1 and 106 from Group 2). Results from each Delphi round were summarised and presented in subsequent rounds until consensus was reached (>70% agreement). Results: The overall response rate for the first Delphi survey was 47% (88/187). The median minimum clinically important effect size was 5.0% (interquartile range: 5.0–10.0) for both stakeholder groups. The overall response rate for the second Delphi survey was 51% (95/187). Consensus was reached after the second round, as 74% of respondents in Group 1 and 82% of respondents in Group 2 agreed with the median effect size. The combined minimum clinically important effect size across both groups was 5.0% (interquartile range: 3.0–6.5). Conclusions: This study demonstrates that surveying stakeholder groups using a Delphi process is a simple way of defining a minimum clinically important effect size, which aids the sample size calculation and determines whether a randomised study is feasible.
Treatment of last resort? Psychological therapy seeking in chronic pain patients
Authors: Farley Dominika , Kłosowska Joanna , Brączyk Justyna , Buglewicz Ewa , Bąbel Przemysław 
Published: May 2023

Objective Our goal was to assess how many chronic pain patients seek psychological treatment for their condition and what psychological and demographic characteristics are associated with that decision. Methods The association between pain intensity, quality of life and psychological treatment seeking was tested in two hypothetical models which differed according to beliefs about either external or internal control over pain. Results A minority of patients had experience with psychological treatment of chronic pain. Patients who had that experience were younger, suffered from more intense pain, and applied many more coping strategies than patients who never tried this kind of treatment. Intense pain and low quality of life motivated chronic pain patients to seek psychological treatment only if they believed that doctors could control their pain. Discussion The study results stress the importance of diversifying the methods used to treat chronic pain and educating patients about the benefits of psychological treatment. Low numbers of chronic pain patients who take advantage of psychological treatment indicate that encouragement from medical professionals might be necessary.
The efficacy of immune checkpoint inhibitors in biliary tract cancer with KRAS mutation
Authors: Jeong Sun Young , Hong Jung Yong , Park Joon Oh , Park Young Suk , Lim Ho Yeong , Jang Jae Yeon , Jeon Youngkyung , Kim Seung Tae 
Published: May 2023

Background: With a 15% incidence, KRAS is one of the most common mutations in biliary tract cancer (BTC) and is a poor prognostic factor. Immune checkpoint inhibitors (ICIs) as salvage therapy have modest activity in BTC. Objectives: There are limited data on the efficacy of ICIs according to KRAS mutation in BTC. We evaluated the efficacy of ICIs in BTC patients with or without KRAS mutations. Design: Retrospective observational study. Methods: We conducted molecular profiling in BTC patients who received ICIs as salvage therapy. The expression of programmed death ligand 1 (PD-L1) on tumor cells was assessed using immunohistochemistry. The TruSightTM Oncology 500 assay from Illumina was used as a cancer panel. We analyzed overall survival (OS) and progression-free survival (PFS) of ICI in BTC patients according to KRAS mutation and PD-L1 expression. Results: A total of 62 patients were included in this analysis. The median age was 68.0 years; 47 patients (75.8%) received pembrolizumab and 15 (24.2%) received nivolumab as salvage therapy. All patients received gemcitabine plus cisplatin as the frontline therapy, and 53.2% received fluoropyrimidine plus oxaliplatin (FOLFOX) before ICI. The median number of lines of prior chemotherapy was 2.5. The KRAS mutation was found in 13 patients (19.1%), and 28 patients (45.2%) showed 1% or more of tumor cells out of visible tumor cells positive for PD-L1. There was no statistical correlation between KRAS mutation and PD-L1 expression. The median OS and PFS with ICI were 5.6 [interquartile range (IQR): 3.3–8.0] and 3.8 (IQR: 3.0–4.5) months, respectively. There were no statistically significant differences in PFS with ICIs according to KRAS mutation (mutant type versus wild type) and PD-L1 expression (positive versus negative). In subgroup analysis, patients with both KRAS mutation and PD-L1 positivity had longer PFS compared with patients with KRAS mutation and PD-L1 negativity (10.1 versus 2.6 months, p = 0.047). This finding was not shown in patients with wild-type KRAS. Conclusion: Our analysis suggested that PD-L1 expression might be a useful biomarker for ICIs in BTC patients with KRAS mutation but not in those with wild-type KRAS.
Mapping splice QTLs reveals distinct transcriptional and post-transcriptional regulatory variation of gene expression and identifies putative alternative splicing variation mediating complex trait variation in pigs
Authors: Zhang Fei , Velez-Irizarry Deborah , Ernst Catherine W. , Huang Wen 
Published: May 2023

Abstract
Background
Alternative splicing is an important step in gene expression, generating multiple isoforms for the same genes and greatly expanding the diversity of proteomes. Genetic variation in alternative splicing contributes to phenotypic diversity in natural populations. However, the genetic basis of variation in alternative splicing in livestock including pigs remains poorly understood.

Results
In this study, using a Duroc x Pietrain F2 pig population, we performed genome-wide analysis of alternative splicing estimated from stranded RNA-Seq data in skeletal muscle. We characterized the genetic architecture of alternative splicing and compared its basic features with those of overall gene expression. We detected a large number of novel alternative splicing events that were not previously annotated. We found heritability of quantitative alternative splicing scores (percent spliced in or PSI) to be lower than that of overall gene expression. In addition, heritabilities showed little correlation between alternative splicing and overall gene expression. We mapped expression QTLs (eQTLs) and splice QTLs (sQTLs) and found them to be largely non-overlapping. Finally, we integrated sQTL mapping with phenotype QTL (pQTL mapping to identify potential mediator of pQTL effect by alternative splicing.

Conclusions
Our results suggest that regulatory variation exists at multiple levels and that their genetic controls are distinct, offering opportunities for genetic improvement.
Impact of a comprehensive cardiac rehabilitation programme versus coronary revascularisation in patients with stable angina pectoris: study protocol for the PRO-FIT randomised controlled trial
Authors: Heutinck Joyce M. , De Koning Iris A. , Vromen Tom , Van Geuns Robert-Jan M. , Thijssen Dick H.J. , Kemps Hareld M.C. ,   On behalf of the PRO-FIT Research Group, Adang Eddy M. , Geleijnse Johanna M. , van Gorp Pieter , van ‘t Hof Arnoud W. J. , Janssen Veronica R. , Jorstad Harald T. , Kraaijenhagen Roderik A. , Lammers Jeroen , de Man Frits H. A. F. , Nollen Gijs J. , van Ofwegen-Hanekamp Clara E. E. , Onkelinx Steven , Oostveen Laurence M. L. C. , Roes Kit C. B. , Sunamara Madoka , Tonino Pim A. L. 
Published: May 2023

Abstract
Background
Currently, in the majority of patients with stable angina pectoris (SAP) treatment consists of optimal medical treatment, potentially followed by coronary angiography and subsequent coronary revascularisation if necessary”. Recent work questioned the effectiveness of these invasive procedures in reducing re-events and improving prognosis. The potential of exercise-based cardiac rehabilitation on clinical outcomes in patients with coronary artery disease is well-known. However, in the modern era, no studies compared the effects of cardiac rehabilitation versus coronary revascularisation in patients with SAP.

Methods
In this multicentre randomised controlled trial, 216 patients with stable angina pectoris and residual anginal complaints under optimal medical treatment will be randomised to: 1) usual care (i.e., coronary revascularisation), or 2) a 12-month cardiac rehabilitation (CR) programme. CR consists of a multidisciplinary intervention, including education, exercise training, lifestyle coaching and a dietary intervention with a stepped decline in supervision. The primary outcome will be anginal complaints (Seattle Angina Questionnaire-7) following the 12-month intervention. Secondary outcomes include cost-effectiveness, ischemic threshold during exercise, cardiovascular events, exercise capacity, quality of life and psychosocial wellbeing.

Discussion
In this study, we will examine the hypothesis that multidisciplinary CR is at least equally effective in reducing anginal complaints as the contemporary invasive approach at 12-months follow-up for patients with SAP. If proven successful, this study will have significant impact on the treatment of patients with SAP as multidisciplinary CR is a less invasive and potentially less costly and better sustainable treatment than coronary revascularisations.

Trial registration
Netherlands Trial Register, NL9537. Registered 14 June 2021.
Comparison of presepsin and Mid-regional pro-adrenomedullin in the diagnosis of sepsis or septic shock: a systematic review and meta-analysis
Authors: Liang Jun , Cai Yingli , Shao Yiming 
Published: May 2023

Abstract
Background
The early diagnosis of sepsis is hampered by the lack of reliable laboratory measures. There is growing evidence that presepsin and Mid-regional pro-adrenomedullin (MR-proADM) are promising biomarkers in the diagnosis of sepsis. This study was conducted to evaluate and compare the diagnostic value of MR-proADM and presepsin in sepsis patients.

Methods
We searched Web of Science, PubMed, Embase, China national knowledge infrastructure, and Wanfang up to 22th July, 2022, for studies evaluating the diagnosis performance of presepsin and MR-proADM in adult sepsis patients. Risk of bias was assessed using quadas-2. Pooled sensitivity and specificity were calculated using bivariate meta-analysis. Meta-regression and subgroup analysis were used to find source of heterogeneity.

Results
A total of 40 studies were eventually selected for inclusion in this meta-analysis, including 33 for presepsin and seven for MR-proADM. Presepsin had a sensitivity of 0.86 (0.82–0.90), a specificity of 0.79 (0.71–0.85), and an AUC of 0.90 (0.87–0.92). The sensitivity of MR-proADM was 0.84 (0.78–0.88), specificity was 0.86 (0.79–0.91), and AUC was 0.91 (0.88–0.93). The profile of control group, population, and standard reference may be potential sources of heterogeneity.

Conclusions
This meta-analysis demonstrated that presepsin and MR-proADM exhibited high accuracy (AUC ≥ 0.90) in the diagnosis of sepsis in adults, with MR-proADM showing significantly higher accuracy than presepsin.
Accessibility of the three-year comprehensive prevention and control of brucellosis in Ningxia: a mathematical modeling study
Authors: Gong Wei , Sun Peng , Zhai Changsheng , Yuan Jing , Chen Yaogeng , Chen Qun , Zhao Yu 
Published: May 2023

AbstractBackgroundBrucellosis is a chronic zoonotic disease, and Ningxia is one of the high prevalence regions in China. To mitigate the spread of brucellosis, the government of Ningxia has implemented a comprehensive prevention and control plan (2022-2024). It is meaningful to quantitatively evaluate the accessibility of this strategy.MethodsBased on the transmission characteristics of brucellosis in Ningxia, we propose a dynamical model of sheep-human-environment, which coupling with the stage structure of sheep and indirect environmental transmission. We first calculate the basic reproduction number$$R_0$$R0and use the model to fit the data of human brucellosis. Then, three widely applied control strategies of brucellosis in Ningxia, that is, slaughtering of sicked sheep, health education to high risk practitioners, and immunization of adult sheep, are evaluated.ResultsThe basic reproduction number is calculated as$$R_{0}=1.47$$R0=1.47, indicating that human brucellosis will persist. The model has a good alignment with the human brucellosis data. The quantitative accessibility evaluation results show that current brucellosis control strategy may not reach the goal on time. “Ningxia Brucellosis Prevention and Control Special Three-Year Action Implementation Plan (2022-2024)” will be achieved in 2024 when increasing slaughtering rate $$\gamma$$γ by 30$$\%$$%, increasing health education to reduce$$\beta _{h}$$βh to 50$$\%$$%, and an increase of immunization rate of adult sheep$$\theta$$θby 40$$\%$$%.ConclusionThe results demonstrate that the comprehensive control measures are the most effective for brucellosis control, and it is necessary to further strengthen the multi-sectoral joint mechanism and adopt integrated measures to prevention and control brucellosis. These results can provide a reliable quantitative basis for further optimizing the prevention and control strategy of brucellosis in Ningxia.
Accuracy of saliva for SARS-CoV-2 detection in outpatients and their household contacts during the circulation of the Omicron variant of concern
Authors: Calvet Guilherme , Ogrzewalska Maria , Tassinari Wagner , Guaraldo Lusiele , Resende Paola , Fuller Trevon , Penetra Stephanie , Borges Michele , Pina-Costa Anielle , Martins Ezequias , Moraes Isabella , Santos Heloisa , Damasceno Luana , Medeiros-Filho Fernando , Espindola Otavio , Mota Fernando , Nacife Valéria , Pauvolid-Corrêa Alex , Whitworth Jimmy , Smith Chris , Siqueira Marilda , Brasil Patrícia 
Published: May 2023

Abstract
Background
While nasopharyngeal (NP) swabs are considered the gold standard for severe acute respiratory coronavirus 2 (SARS-CoV-2) real-time reverse transcriptase-polymerase chain reaction (RT-PCR) detection, several studies have shown that saliva is an alternative specimen for COVID-19 diagnosis and screening.

Methods
To analyze the utility of saliva for the diagnosis of COVID-19 during the circulation of the Omicron variant, participants were enrolled in an ongoing cohort designed to assess the natural history of SARS-CoV-2 infection in adults and children. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and Cohen’s kappa coefficient were calculated to assess diagnostic performance.

Results
Overall, 818 samples were collected from 365 outpatients from January 3 to February 2, 2022. The median age was 32.8 years (range: 3–94 years). RT-PCR for SARS-CoV-2 was confirmed in 97/121 symptomatic patients (80.2%) and 62/244 (25.4%) asymptomatic patients. Substantial agreement between saliva and combined nasopharyngeal/oropharyngeal samples was observed with a Cohen’s kappa value of 0.74 [95% confidence interval (CI): 0.67–0.81]. Sensitivity was 77% (95% CI: 70.9–82.2), specificity 95% (95% CI: 91.9–97), PPV 89.8% (95% CI: 83.1–94.4), NPV 87.9% (95% CI: 83.6–91.5), and accuracy 88.5% (95% CI: 85.0-91.4). Sensitivity was higher among samples collected from symptomatic children aged three years and older and adolescents [84% (95% CI: 70.5–92)] with a Cohen’s kappa value of 0.63 (95% CI: 0.35–0.91).

Conclusions
Saliva is a reliable fluid for detecting SARS-CoV-2, especially in symptomatic children and adolescents during the circulation of the Omicron variant.
Prevalence and related factors of inappropriate gestational weight gain among pregnant women with overweight/ obesity in Thailand
Authors: Chairat Thanyawalai , Ratinthorn Ameporn , Limruangrong Piyanun , Boriboonhirunsarn Dittakarn 
Published: May 2023

Abstract
Background
An inappropriate gestational weight gain (GWG) among pregnant women with overweight/obesity is a crucial health problem. Its prevalence remains high worldwide, particularly in urban areas. The prevalence and predicting factors in Thailand are lack of evidence. This study aimed to investigate prevalence rates, antenatal care (ANC) service arrangement, predictive factors, and impacts of inappropriate GWG among pregnant women with overweight/obesity in Bangkok and its surrounding metropolitan area.

Methods
This cross-sectional, retrospective study used four sets of questionnaires investigating 685 pregnant women with overweight/obesity and 51 nurse-midwives (NMs) from July to December 2019 in ten tertiary hospitals. Multinomial logistic regression identified predictive factors with a 95% confidence interval (CI).

Result
The prevalence rates of excessive and inadequate GWG were 62.34% and 12.99%. Weight management for pregnant women with overweight/obesity are unavailable in tertiary cares. Over three-fourths of NMs have never received weight management training for this particular group. ANC service factors, i.e., GWG counseling by ANC providers, quality of general ANC service at an excellent and good level, NMs' positive attitudes toward GWG control, significantly decreased the adjusted odds ratio (AOR) of inadequate GWG by 0.03, 0.01, 0.02, 0.20, times, respectively. While maternal factors, sufficient income, and easy access to low-fat foods reduce AOR of inadequate GWG by 0.49, and 0.31 times. In contrast, adequate maternal GWG knowledge statistically increased the AOR of inadequate GWG 1.81 times. Meanwhile, easy access to low-fat foods and internal weight locus of control (WLOC) decreased the AOR of excessive GWG by 0.29 and 0.57 times. Finally, excessive GWG significantly increased the risk of primary C/S, fetal LGA, and macrosomia 1.65, 1.60, and 5.84 times, respectively, while inadequate GWG was not associated with adverse outcomes.

Conclusion
Prevalence rates of inappropriate GWG, especially excessive GWG remained high and affected adverse outcomes. The quality of ANC service provision and appropriate GWG counseling from ANC providers are significant health service factors. Thus, NMs should receive gestational weight counseling and management training to improve women's knowledge and practice for gestational weight (GW) control.
Maternal and newborn healthcare utilization in Kampala urban slums: perspectives of women, their spouses, and healthcare providers
Authors: Magunda Andrew , Ononge Sam , Balaba Dorothy , Waiswa Peter , Okello Daniel , Kaula Henry , Keller Brett , Felker-Kantor Erica , Mugerwa Yvonne , Bennett Cudjoe 
Published: May 2023

Abstract
Background
It is assumed that the health conditions of urban women are superior to their rural counterparts. However, evidence from Asia and Africa, show that poor urban women and their families have worse access to antenatal care and facility childbirth compared to the rural women. The maternal, newborn, and child mortality rates as high as or higher than those in rural areas. In Uganda, maternal and newborn health data reflect similar trend. The aim of the study was to understand factors that influence use of maternal and newborn healthcare in two urban slums of Kampala, Uganda.

Methods
A qualitative study was conducted in urban slums of Kampala, Uganda and conducted 60 in-depth interviews with women who had given birth in the 12 months prior to data collection and traditional birth attendants, 23 key informant interviews with healthcare providers, coordinator of emergency ambulances/emergency medical technicians and the Kampala Capital City Authority health team, and 15 focus group discussions with partners of women who gave birth 12 months prior to data collection and community leaders. Data were thematically coded and analyzed using NVivo version 10 software.

Results
The main determinants that influenced access to and use of maternal and newborn health care in the slum communities included knowledge about when to seek care, decision-making power, financial ability, prior experience with the healthcare system, and the quality of care provided. Private facilities were perceived to be of higher quality, however women primarily sought care at public health facilities due to financial constraints. Reports of disrespectful treatment, neglect, and financial bribes by providers were common and linked to negative childbirth experiences. The lack of adequate infrastructure and basic medical equipment and medicine impacted patient experiences and provider ability to deliver quality care.

Conclusions
Despite availability of healthcare, urban women and their families are burdened by the financial costs of health care. Disrespectful and abusive treatment at hands of healthcare providers is common translating to negative healthcare experiences for women. There is a need to invest in quality of care through financial assistance programs, infrastructure improvements, and higher standards of provider accountability are needed.
Implanting toric implantable collamer lens displays better astigmatism correction than implantable collamer lens combined with manually limbal relaxing incision
Authors: Yang Ke , Li Jiaxin , Zhang Weihua , Liu Zhanjiang , Song Chenjie , Zhao Yang 
Published: May 2023

Abstract
Background
This retrospective study aimed to compare the outcomes of toric implantable collamer lens (TICL) surgery with those of implantable collamer lens (ICL) implantation combined with limbal relaxing incision (LRI) in patients with low myopia and astigmatism.

Methods
A total of 40 eyes of 28 patients who underwent TICL implantation and 40 eyes of 27 patients who underwent ICL implantation combined with manually LRI between 2021 and 2022 were included. Primary outcomes were manifest sphere and cylinder, intraocular pressure, visual acuity, and astigmatism parameters at 1 day, 1 week, and 1, 3, and 6 months postoperatively.

Results
The two surgeries showed comparable effects on manifest sphere and cylinder, intraocular pressure, and visual acuity (all p > 0.1). Surgery-induced astigmatism (SIA) was maintained as stable in the TICL group (1.73 to 1.68, p = 0.420), but was significantly reduced in the ICL/LRI group (1.74 to 1.17, p = 0.001) from preoperative to postoperative 6 months. The TICL group displayed significantly higher SIA and correction index at postoperative 1, 3, and 6 months than the ICL/LRI group (at 6 months: SIA, 1.68 (1.26, 1.96) vs., 1.17 (1.00, 1.64), p = 0.010; CI: 0.98 (0.78, 1.25) vs. 0.80 (0.61, 1.04), p = 0.018). No complications occurred during follow-up.

Conclusions
The effects of ICL/LRI are comparable to those of TICL in correcting myopia. TICL implantation displays better astigmatism correction than ICL/LRI.