bluuebunny/crossref_metadata_2025_split huggingface dataset:
Harmonisation of large-scale, heterogeneous individual participant adverse event data from randomised trials of statin therapy
Authors: Cholesterol Treatment Trialists’ Collaboration  
Published: July 2022

Background: Meta-analyses of individual-level data from randomised trials are often required to detect clinically worthwhile effects. The Cholesterol Treatment Trialists’ Collaboration, which includes data from numerous large long-term statin trials, is conducting a review of the effects of statin therapy on all adverse events collected in those trials. This article describes the approaches used and challenges faced to systematically capture and categorise the data. Methods: Protocols, statistical analysis plans, case report forms, clinical study reports and datasets were obtained, reviewed and checked. Relevant baseline and follow-up data from each trial was then reorganised into standardised formats based upon the Clinical Data Interchange Standards Consortium Study Data Tabulation Model. Adverse event data were organised and coded (automatically or, where necessary, manually) according to a common medical dictionary based upon the Medical Dictionary for Regulatory Activities. Results: Data from 23 double-blind statin trials and 5 open-label statin trials were provided, either through direct data transfer or through online access platforms. Together, these trials provided 845 datasets containing over 38 million records relating to 30,495 study variables and 181,973 randomised participants. Of the 46 Clinical Data Interchange Standards Consortium Study Data Tabulation Model domains that could potentially have been used to organise the data, the 13 most relevant to the project were identified and utilised, including 6 domains related to post-randomisation adverse events. Nearly 1.2 million adverse events were extracted and mapped to over 45,000 unique adverse event terms. Of these adverse events, 99% were coded to a Medical Dictionary for Regulatory Activities ‘lower level term’, with the remainder coded to a ‘higher level term’ or, very rarely, only a ‘higher level group term’. Conclusion: In this meta-analysis of adverse event data from the large randomised trials of statins, approaches based on common standards for data organisation and classification have provided a resource capable of allowing reliable and rapid evaluation of any previously unknown benefits or hazards of statin therapy.
Effect of inhaled budesonide/formoterol fumarate dihydrate delivered via two different devices on lung function in patients with COPD and low peak inspiratory flow
Authors: Huber Bärbel , Keller Claus , Jenkins Martin , Raza Abid , Aurivillius Magnus 
Published: July 2022

Background and aims: Low peak inspiratory flow (PIF) is common following severe exacerbations of chronic obstructive pulmonary disease (COPD). Patients with COPD and low PIF may be at risk of suboptimal delivery of inhaled therapies to the airways, especially when using devices such as dry powder inhalers (DPIs), which require greater inspiratory effort than metered dose inhalers (MDIs). We report the results from a 2-week crossover study evaluating the effects of inhaled dual therapy with budesonide/formoterol fumarate dihydrate with an MDI with a spacer versus a DPI in patients with COPD and low PIF. Methods: This randomized, open-label, two-period (each 1 week in duration) crossover efficacy and safety study included patients with severe-to-very severe COPD and PIF < 50 L/min (NCT04078126). Patients were randomized 1:1 to twice-daily budesonide/formoterol fumarate dihydrate MDI (BFF MDI) 320/10 µg with a spacer for 1 week followed by twice-daily budesonide/formoterol fumarate dihydrate DPI (BUD/FORM DPI) 320/9 µg for 1 week, or the inverse. The primary endpoint was peak change from baseline in forced expiratory volume in 1 s (FEV1) within 4 h post-dose following 1 week of treatment. Other assessments included pre-dose lung function, pharmacokinetics, and safety, as assessed by adverse events. Results: The modified intention-to-treat analysis set comprised 30 patients (mean age: 66.9 years; mean baseline FEV1: 766 mL; mean COPD assessment test score: 22.20). Following 1 week of treatment, both BFF MDI and BUD/FORM DPI improved mean [95% confidence interval (CI)] peak FEV1 4 h post-dose [256 (190, 322) mL and 274 (208, 340) mL, respectively]. No clinically meaningful difference between treatments was observed for any lung function endpoint. There were no unexpected safety findings. Conclusion: Dual therapy with BFF MDI and with BUD/FORM DPI led to improvements in lung function in patients with severe-to-very severe COPD and low PIF.
Noninvasive Glucose Measurements Through Transcutaneous Raman Spectroscopy: A Review
Authors: Loyola-Leyva Alejandra , Hernández-Vidales Karen , Loyola-Rodríguez Juan Pablo , González Francisco Javier 
Published: July 2022

Background: People living with diabetes need constant glucose monitoring to avoid health complications. However, they do not monitor their glucose levels as often as recommended, probably because glucose measurement devices can be painful, costly, need testing strips or sensors, require lancing the finger or inserting a sensor with risk of infection, and can be inaccurate or have failures. Therefore, developing new alternatives for noninvasive glucose measurements that overcome these disadvantages is necessary, being Raman spectroscopy (RS) a solution. Objective: This review aims to provide an overview of the current glucose-monitoring technologies and the uses and advantages of RS to improve noninvasive transcutaneously glucose-monitoring devices. Results: The skin has been used to assess glucose levels noninvasively because it is an accessible tissue where glucose can be measured in the interstitial fluid (ISF) in the epidermis (especially in the stratum corneum). The most selected skin sites to apply RS for noninvasive glucose measurements were the nailfold, finger, and forearm because, in these sites, the penetration depth of the excitation light can reach the stratum corneum (10-20 µm) and the ISF. Studies found that RS is a good optical technique to measure glucose noninvasively by comparing glucose levels obtained by RS with those from invasive methods such as glucose meters with testing strips during an oral glucose tolerance test (OGTT). Conclusions: New alternatives for noninvasive glucose measurements that overcome the disadvantages of current devices is necessary, and RS is a possible solution. However, more research is needed to evaluate the stability, accuracy, costs, and acceptance.
Personalizing the Use of a Intermittently Scanned Continuous Glucose Monitoring Device in Individuals With Type 1 Diabetes: A Cost-Effectiveness Perspective in the Netherlands (FLARE-NL 9)
Authors: Emamipour Sajad , van Dijk Peter R. , Bilo Henk J.G. , Edens Mireille A. , van der Galiën Onno , Postma Maarten J. , Feenstra Talitha L. , van Boven Job F. M. 
Published: July 2022

Aims: Intermittently scanned continuous glucose monitoring (isCGM) is a method to monitor glucose concentrations without using a finger prick. Among persons with type 1 diabetes (T1D), isCGM results in improved glycemic control, less disease burden and improved health-related quality of life (HRQoL). However, it is not clear for which subgroups of patients isCGM is cost-effective. We aimed to provide a real-world cost-effectiveness perspective. Methods: We used clinical data from a 1-year nationwide Dutch prospective observational study (N = 381) and linked these to insurance records. Health-related quality of life was assessed with the EQ-5D-3L questionnaire. Individuals were categorized into 4 subgroups: (1) frequent hypoglycemic events (58%), (2) HbA1c > 70 mmol/mol (8.5%) (19%), (3) occupation that requires avoiding finger pricks and/or hypoglycemia (5%), and (4) multiple indications (18%). Comparing costs and outcomes 12 months before and after isCGM initiation, incremental cost-effectiveness ratios (ICERs) were calculated for the total cohort and each subgroup from a societal perspective (including healthcare and productivity loss costs) at the willingness to pay of €50,000 per quality-adjusted life year (QALY) gained. Results: From a societal perspective, isCGM was dominant in all subgroups (ie higher HRQoL gain with lower costs) except for subgroup 1. From a healthcare payer perspective, the probabilities of isCGM being cost-effective were 16%, 9%, 30%, 98%, and 65% for the total cohort and subgroup 1, 2, 3, and 4, respectively. Most sensitivity analyses confirmed these findings. Conclusions: Comparing subgroups of isCGM users allows to prioritize them based on cost-effectiveness. The most cost-effective subgroup was occupation-related indications, followed by multiple indications, high HbA1c and the frequent hypoglycemic events subgroups. However, controlled studies with larger sample size are needed to draw definitive conclusions.
Metformin and the risk of dementia based on an analysis of 396,332 participants
Authors: Ji Shiliang , Zhao Xingxing , Zhu Ruifang , Dong Yongchao , Huang Lifeng , Zhang Taiquan 
Published: July 2022

Background: AMPK has attracted widespread interest as a potential therapeutic target for age-related diseases, given its key role in controlling energy homeostasis. Metformin (Met) has historically been used to treat Type 2 diabetes and has been shown to counteract age-related diseases. However, studies regarding the relationship between Met and a variety of age-related classifications of cognitive decline have reported mixed findings. Objective: To assess the potential effect of Met on the onset of dementia and discuss the possible biological mechanisms involved. Methods: This study was registered in the PROSPERO database (CRD420201251468). PubMed, Embase, and Cochrane Library were searched from inception to 25 May 2021, for population-based cohort studies. Effect estimates with 95% confidence intervals (CIs) were pooled using the random-effects model. Meta-regression and subgroup analyses were performed to explore sources of heterogeneity and the stability of the results. Results: Fourteen population-based cohort studies (17 individual comparisons) involving 396,332 participants were identified. Meta-analysis showed that Met exposure was significantly associated with reduced risk of all subtypes of dementias [relative risk (RR) = 0.79, 95% CI = 0.68–0.91; p < 0.001]. Conversely, no significant reduction in risk was observed for those who received Met monotherapy at the onset of vascular dementia (VD), Parkinson’s disease (PD), and Alzheimer’s disease (AD). The effect was more prominent in patients who had long-term Met exposure (⩾4 years) (RR = 0.38, 95% CI = 0.32–0.46; p < 0.001), while no such significant effect was found with short-term Met exposure (1–2 years) (RR = 1.20, 95% CI = 0.87–1.66; p < 0.001). Moreover, no association was observed for Met exposure in participants of European descent (RR = 1.01, 95% CI = 0.66–1.54; p = 0.003) compared with those from other countries. Conclusion: Based on the evidence from population-based cohort studies, our findings suggest that the AMPK activator, Met, is a potential geroprotective agent for dementias, particularly among long-term Met users. Due to the significant heterogeneity among the included studies, we should interpret the results with caution.
Magnitude of neonatal near miss in public hospitals in Eastern Ethiopia: A cross-sectional study
Authors: Tola Melese Adugna , Semahegn Agumasie , Tiruye Getahun , Tura Abera Kenay 
Published: July 2022

Objectives: Although neonatal near miss is an emerging concept and a tool for improving neonatal care, its magnitude and associated factors are less researched in Ethiopia. Thus, this study was aimed to uncover the magnitude of neonatal near miss and its associated factors in public hospitals in Eastern Ethiopia. Methods: A facility-based cross-sectional study was employed on a randomly selected 405 mother–neonate pairs. An interview using a structured questionnaire accompanied by review of medical records was used to collect data from the mothers and records of the neonates. Neonatal near miss was defined as having any of the pragmatic (gestational age < 33 weeks, birth weight < 1750 g, and fifth minutes Apgar score < 7) or management criteria. Crude and adjusted logistic regression analysis was done to identify associated factors and presented with adjusted odds ratio with 95% confidence interval. Results: Of 401 mother–neonate pairs included in the study, 126 (31.4%, 95% confidence interval = [26.9, 36.2]) neonates had at least one neonatal near miss event at discharge. Neonatal near miss was more likely among neonates from referred women (adjusted odds ratio = 2.24, 95% confidence interval = [1.25, 4.03]), no antenatal care (adjusted odds ratio = 2.08, 95% confidence interval = [1.10, 3.93]), antepartum hemorrhage (adjusted odds ratio = 4.29, 95% confidence interval = [2.16, 8.53]), premature rupture of membrane (adjusted odds ratio = 4.07, 95% confidence interval = [2.05, 8.07]), obstructed labor (adjusted odds ratio = 2.61, 95% confidence interval = [1.23, 5.52]), non-vertex presentation (adjusted odds ratio = 3.03, 95% confidence interval = [1.54, 5.95]), and primiparous (adjusted odd ratio = 2.67, 95% confidence interval = [1.49, 4.77]). Conclusions: In this study, we found that neonatal near miss is higher than previous findings in Ethiopia. Improving neonatal near miss requires promoting antenatal care, maternal referral system, and early identification and management of obstetric complications.
Trocar-Based Surgical Approach to Suprachoroidal Hemorrhage Drainage
Authors: Pericak Olivia , Chin Eric K. , Almeida David R.P. 
Published: July 2022

Purpose: Suprachoroidal hemorrhage is an uncommon but serious ocular condition that typically occurs in the setting of intraocular surgery and trauma. We present an external trans-conjunctival vitreoretinal trocar-cannula-based drainage of suprachoroidal hemorrhage as a viable surgical approach. Methods: Case report. Results: Trans-conjunctival trocar-cannula-based drainage of suprachoroidal hemorrhage is a safe and efficacious surgical approach to drainage of large choroidal hemorrhages. Conclusions: Although discrepancies persist regarding the optimal surgical approach to suprachoroidal hemorrhage management; herein, we describe the successful execution of an external trans-conjunctival vitreoretinal trocar-cannula-based drainage of suprachoroidal hemorrhage.
Profiling Gingivoperiosteoplasty (GPP): A Cross-Sectional Analysis Using a Nationally Validated Pediatric Surgery Database
Authors: Arias Fernando D. , Rochlin Danielle H. , Rabbani Piul S. , Shetye Pradip R. , Staffenberg David A. , Flores Roberto L. 
Published: July 2022

Objective: Compare short term surgical outcomes and trends in cleft lip repair with or without gingivoperiosteoplasty (GPP). Design: Retrospective review of the ACS NSQIP-Pediatric database from 2014 to 2019. Patients: Patients between 2 and 18 months of age undergoing any initial cleft lip repair, with or without GPP, were selected via relevant CPT® codes. Main Outcome Measures: Patient demographics, comorbidities, 30-day readmissions and post-operative complications are assessed. Results: From 2014 to 2019, a total of 6269 patients were identified, of which 6.67% underwent GPP (n = 418). Patients undergoing GPP were significantly older with an average age of 9 months compared to 5 months in the non-GPP group ( P < .001). Co-morbidities were similar amongst both cohorts, although patients undergoing GPP were more likely to have a higher ASA class ( P = .006), cardiac risk factors ( P = .012) and syndromic diagnosis ( P < .001). There were no differences in 30-day short term surgical outcomes. GPP was associated with increased operative time by ~25 minutes when compared to cleft lip repair alone ( P < .001). Conclusion: GPP was not associated with increased 30-day postoperative complications, readmission, reoperation, or total length of hospital stay, and was associated with an increased operative time of 25 minutes. Children undergoing GPP were significantly older in age and were more likely to have a higher ASA class/cardiac risk factors.
Selective versus non-selective NSAIDs as prophylaxis for heterotopic ossification following hip arthroplasty: a meta-analysis
Authors: Migliorini Filippo , Pintore Andrea , Baroncini Alice , Pastor Torsten , Hildebrand Frank , Maffulli Nicola 
Published: July 2022

Abstract
Background
Some patients have demonstrated evidence of heterotopic ossification (HO) following total hip arthroplasty (THA). Selective and non-selective non-steroidal anti-inflammatory drugs (NSAIDs) are used as prophylaxis for HO following THA. This meta-analysis compared selective versus non-selective NSAIDs as prophylaxis for HO following THA.

Material and methods
The present study was conducted according to the PRISMA 2020 guidelines. All the clinical investigations comparing selective versus non-selective NSAIDs as prophylaxis for HO following THA were accessed in February 2022. An assessment of the methodological quality and statistical analyses were performed through the risk of bias summary tool of the Review Manager 5.3 software (Cochrane Collaboration, Copenhagen). The modified Brooker staging system was used to rate the efficacies of the interventions.

Results
Data from 8 studies and 1526 patients were collected. 60.8% were female. No difference was found in the sample size, mean age, and percentage of females between the two groups at baseline. No statistically significant difference was found between selective and non-selective NSAIDs in term of efficacy. 72% (1078 of 1502) of the patients were classified as Brooker 0, 21% (322 of 1502) as Brooker I, 5% (80 of 1502) as Brooker II, 1% (16 of 1502) as Brooker III, and 0.1% (2 of 1502) as Brooker IV.

Conclusion
Selective and non-selective NSAIDs were equally effective when used as prophylaxis for HO following THA.

Level of evidence
Level III, systematic review and meta-analysis.
The evolutionary history of cribellate orb-weaver capture thread spidroins
Authors: Correa-Garhwal Sandra M. , Baker Richard H. , Clarke Thomas H. , Ayoub Nadia A. , Hayashi Cheryl Y. 
Published: July 2022

AbstractBackgroundSpiders have evolved two types of sticky capture threads: one with wet adhesive spun by ecribellate orb-weavers and another with dry adhesive spun by cribellate spiders. The evolutionary history of cribellate capture threads is especially poorly understood. Here, we use genomic approaches to catalog the spider-specific silk gene family (spidroins) for the cribellate orb-weaverUloborus diversus.ResultsWe show that the cribellar spidroin, which forms the puffy fibrils of cribellate threads, has three distinct repeat units, one of which is conserved across cribellate taxa separated by ~ 250 Mya. We also propose candidates for a new silk type, paracribellar spidroins, which connect the puffy fibrils to pseudoflagelliform support lines. Moreover, we describe the complete repeat architecture for the pseudoflagelliform spidroin (Pflag), which contributes to extensibility of pseudoflagelliform axial fibers.ConclusionsOur finding that Pflag is closely related to Flag, supports homology of the support lines of cribellate and ecribellate capture threads. It further suggests an evolutionary phase following gene duplication, in which both Flag and Pflag were incorporated into the axial lines, with subsequent loss of Flag in uloborids, and increase in expression of Flag in ecribellate orb-weavers, explaining the distinct mechanical properties of the axial lines of these two groups.
Compromised cardiopulmonary resuscitation quality due to regurgitation during endotracheal intubation: a randomised crossover manikin simulation study
Authors: Lin Li-Wei , DuCanto James , Hsu Chen-Yang , Su Yung-Cheng , Huang Chi-Chieh , Hung Shih-Wen 
Published: July 2022

Abstract
Background
Regurgitation is a complication common during cardiopulmonary resuscitation (CPR). This manikin study evaluated the effect of regurgitation during endotracheal intubation on CPR quality.

Methods
An airway-CPR manikin was modified to regurgitate simulated gastric contents into the oropharynx during chest compression during CPR. In total, 54 emergency medical technician-paramedics were assigned to either an oropharyngeal regurgitation or clean airway scenario and then switched to the other scenario after finishing the first. The primary outcomes were CPR quality metrics, including chest compression fraction (CCF), chest compression depth, chest compression rate, and longest interruption time. The secondary outcomes were intubation success rate and intubation time.

Results
During the first CPR–intubation sequence, the oropharyngeal regurgitation scenario was associated with a significantly lower CCF (79.6% vs. 85.1%, P < 0.001), compression depth (5.2 vs. 5.4 cm, P < 0.001), and first-pass success rate (35.2% vs. 79.6%, P < 0.001) and greater longest interruption duration (4.0 vs. 3.0 s, P < 0.001) than the clean airway scenario. During the second and third sequences, no significant difference was observed in the CPR quality metrics between the two scenarios. In the oropharyngeal regurgitation scenario, successful intubation was independently and significantly associated with compression depth (hazard ratio = 0.47, 95% confidence interval, 0.24–0.91), whereas none of the CPR quality metrics were related to successful intubation in the clean airway scenario.

Conclusion
Regurgitation during endotracheal intubation significantly reduces CPR quality.

Trial registration
ClinicalTrials.gov, NCT05278923, March 14, 2022.
Structural brain network measures in elderly patients with cerebral small vessel disease and depressive symptoms
Authors: Gu Yumeng , Zhao Ping , Feng Wenjun , Xia Xiaoshuang , Tian Xiaolin , Yan Yu , Wang Xiaowen , Gao Decheng , Du Yanfen , Li Xin 
Published: July 2022

Abstract
Objectives
To investigate the relationship between diffusion tensor imaging (DTI) indicators and cerebral small vessel disease (CSVD) with depressive states, and to explore the underlying mechanisms of white matter damage in CSVD with depression.

Method
A total of 115 elderly subjects were consecutively recruited from the neurology clinic, including 36 CSVD patients with depressive state (CSVD+D), 34 CSVD patients without depressive state (CSVD-D), and 45 controls. A detailed neuropsychological assessment and multimodal magnetic resonance imaging (MRI) were performed. Based on tract-based spatial statistics (TBSS) analysis and structural network analysis, differences between groups were compared, including white matter fiber indicators (fractional anisotropy and mean diffusivity) and structural brain network indicators (global efficiency, local efficiency and network strength), in order to explore the differences and correlations of DTI parameters among the three groups.

Results
There were no significant differences in terms of CSVD burden scores and conventional imaging findings between the CSVD-D and CSVD+D groups. Group differences were found in DTI indicators (p <  0.05), after adjusting for age, gender, education level, and vascular risk factors (VRF), there were significant correlations between TBSS analysis indicators and depression, including: fractional anisotropy (FA) (r = − 0.291, p <  0.05), mean diffusivity (MD) (r = 0.297, p < 0.05), at the same time, between structural network indicators and depression also show significant correlations, including: local efficiency (ELocal) (r = − 0.278, p < 0.01) and network strength (r = − 0.403, p < 0.001).

Conclusions
Changes in FA, MD values and structural network indicators in DTI parameters can predict the depressive state of CSVD to a certain extent, providing a more direct structural basis for the hypothesis of abnormal neural circuits in the pathogenesis of vascular-related depression. In addition, abnormal white matter alterations in subcortical neural circuits probably affect the microstructural function of brain connections, which may be a mechanism for the concomitant depressive symptoms in CSVD patients.