bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prevalence and management of familial hypercholesterolaemia in patients with chest pain admitted to hospital: a retrospective observational study
Authors: Mülverstedt Stefan , Prescott Eva Irene Bossano , Jørgensen Henrik , Heitmann Merete 
Published: February 2024

ObjectivesPatients with familial hypercholesterolaemia (FH) are genetically burdened by a lifelong elevation of the low-density lipoprotein cholesterol (LDL-C) level, putting them at a very high risk of premature ischaemic heart disease (IHD). This study aims to assess the prevalence of FH among patients admitted for IHD and the preventive treatment status before admission.DesignObservational, retrospective, register-based study.SettingIndividuals discharged with a diagnosis of IHD were enrolled consecutively throughout 2012–2016 from the cardiac care units of two hospitals in Copenhagen.Participants4223 individuals were discharged during the period. Inclusion criteria for further investigation were the availability of one measurement of LDL-C at the time of admission. In total, 2797 individuals were included for further investigation. There were no exclusion criteria.Primary and secondary outcome measuresThe primary objective has been to determine the prevalence of FH in the population. The secondary objective has been to determine the use of lipid-lowering therapy and to which extend the individuals reach their treatment goal.ResultsAmong the 2797 consecutive patients evaluated, the prevalence of potential FH was 7.7% (1: 13) and 6.8% (1:15) had probably or definite FH. The prevalence of FH was age-dependent: Among the 680 patients (24.3%) with premature IHD (men <55 years/women <60 years), 136 patients (20.0%) had potential FH and 21 (3.1%) had probable/definite FH. None were diagnosed and almost none attained their treatment goal.ConclusionsThere is still a massive lack of recognition of FH in patients admitted to a cardiac care unit with a diagnosis of IHD. Despite a measured high LDL-C, the diagnosis was not made for any patients not even in patients who were admitted at an early age or had a previous cardiovascular event.
Improving the emergency services using quality improvement project and Donabedian model in a quaternary teaching hospital in South India
Authors: Goenka Apoorva , Mundkur Suneel , Sujir Nayak Sachin , Shetty Avinash , Thomas Jibu , Mymbilly Balakrishnan Jayaraj , Chandra Sekaran Varalakshmi , Dsouza Brayal 
Published: February 2024

IntroductionThe primary goal of quality improvement is to enhance patient outcomes, particularly in the emergency department (ED). Timely and effective care is crucial in these situations. By comprehending the challenges, evaluating current performance and implementing quality improvement projects, areas in need of enhancement can be pinpointed and addressed, resulting in better outcomes.MethodologyThis interventional study explores the implementation of quality improvement in the ED of a quaternary care teaching hospital in South India. It follows the Plan-Do-Check-Act (PDCA) cycle guided by the Donabedian model. Descriptive statistics were employed to measure changes in outcomes before and after implementation. To improve processes, Donabedian principles were applied, and a performance audit was conducted based on patient feedback and stakeholder input. Various ED indicators were measured. To address identified issues, formal root cause analysis was performed, leading to the generation of PDCA rapid change cycles. These cycles were implemented over 6 months, with two cycles executed, followed by postimplementation evaluation.ResultsPost implementation, improvements were observed in several aspects of ED operations. These included reduced ED average length of stay, decreased time to analgesia, shorter cross-consultation time, faster transfer time from ED and improved investigation turnaround time (TAT). Additionally, there was a reduction in revisits to ED within 72 hours and a decrease in patients who left without being seen. These positive changes demonstrate the effectiveness of the quality improvement intervention using the PDCA cycle.ConclusionA comprehensive understanding of patient profile in the ED and factors influencing care is essential for the hospital to ensure sufficient resources and skilled emergency medicine physicians are available 24/7. By enhancing services in the ED, reducing patient waiting times and improving TAT, the overall efficiency of services can be improved. This leads to provision of timely quality care to patients and ultimately improves their outcomes.
Increasing rates of screening and treatment of iron deficiency in ambulatory patients with heart failure with reduced ejection fraction: a quality improvement cohort study
Authors: Gewarges Mena , Mainland Roslyn , Wilkinson Katherine , Sklar Jaime , Gentilin Andrew , McLean Bianca , Hajjaj Omar I , Worme Mali , Lalonde Spencer , Patel Raumil , Lin Yulia , Callum Jeannie , Poon Stephanie 
Published: February 2024

IntroductionIron deficiency anaemia (IDA) is common in patients with heart failure (HF) and is associated with advanced HF and increased mortality. Intravenous iron supplementation increases exercise tolerance, improves quality of life, and decreases symptoms among patients with HF with reduced ejection fraction (HFrEF) and iron deficiency. Despite this, many patients are not screened or treated for IDA. We aimed to increase rates of screening and treatment of IDA among HF patients through the introduction of curated materials to aid HF clinicians with appropriate screening and treatment.MethodsWe conducted a retrospective chart review to identify the baseline number of HFrEF patients screened and treated for IDA at two ambulatory cardiology clinics in Toronto, Ontario. A quality improvement initiative was then introduced, which consisted of education and curated materials to aid clinicians in the screening and treatment of IDA among HFrEF patients. The proportion of patients screened and treated for IDA preintervention and postintervention were compared using χ2tests of Independence.ResultsIn the preintervention cohort, 36.3% (n=45) of patients with anaemia were screened for IDA. Among those screened, 64.4% (n=29) had IDA. Only 17.2% (n=5) of these were treated with IV iron. After implementation of the quality improvement initiative, 90.9% (n=60) of patients with anaemia were screened for IDA (p<0.001) and 90.3% (n=28) of those with IDA were treated with IV iron (p<0.001).ConclusionThe introduction of curated materials to aid clinicians was associated with increased rates of screening and treatment of IDA among ambulatory HFrEF patients. Further work is required to identify barriers and implement strategies to increase screening and treatment rates of IDA among HFrEF patients.
Between-hospital variation in indicators of quality of care: a systematic review
Authors: van der Linde Margrietha , Salet Nèwel , van Leeuwen Nikki , Lingsma Hester F , Eijkenaar Frank 
Published: February 2024

BackgroundEfforts to mitigate unwarranted variation in the quality of care require insight into the ‘level’ (eg, patient, physician, ward, hospital) at which observed variation exists. This systematic literature review aims to synthesise the results of studies that quantify the extent to which hospitals contribute to variation in quality indicator scores.MethodsEmbase, Medline, Web of Science, Cochrane and Google Scholar were systematically searched from 2010 to November 2023. We included studies that reported a measure of between-hospital variation in quality indicator scores relative to total variation, typically expressed as a variance partition coefficient (VPC). The results were analysed by disease category and quality indicator type.ResultsIn total, 8373 studies were reviewed, of which 44 met the inclusion criteria. Casemix adjusted variation was studied for multiple disease categories using 144 indicators, divided over 5 types: intermediate clinical outcomes (n=81), final clinical outcomes (n=35), processes (n=10), patient-reported experiences (n=15) and patient-reported outcomes (n=3). In addition to an analysis of between-hospital variation, eight studies also reported physician-level variation (n=54 estimates). In general, variation that could be attributed to hospitals was limited (median VPC=3%, IQR=1%–9%). Between-hospital variation was highest for process indicators (17.4%, 10.8%–33.5%) and lowest for final clinical outcomes (1.4%, 0.6%–4.2%) and patient-reported outcomes (1.0%, 0.9%–1.5%). No clear pattern could be identified in the degree of between-hospital variation by disease category. Furthermore, the studies exhibited limited attention to the reliability of observed differences in indicator scores.ConclusionHospital-level variation in quality indicator scores is generally small relative to residual variation. However, meaningful variation between hospitals does exist for multiple indicators, especially for care processes which can be directly influenced by hospital policy. Quality improvement strategies are likely to generate more impact if preceded by level-specific and indicator-specific analyses of variation, and when absolute variation is also considered.PROSPERO registration numberCRD42022315850.
Association between pulmonary function and rapid kidney function decline: a longitudinal cohort study from CHARLS
Authors: Han Shisheng , Xu Yanqiu , Wang Yi 
Published: February 2024

BackgroundPulmonary function has been reported to be associated with chronic kidney disease. However, the relationship between lung function and rapid kidney function decline remains unclear.MethodsParticipants aged ≥45 years with complete data from the 2011 and 2015 interviews of the China Health and Retirement Longitudinal Study (CHARLS) were included. Lung function, assessed by peak expiratory flow (PEF), and kidney function, assessed by estimated glomerular filtration rate (eGFR), were tested at the baseline and endpoint surveys. Rapid kidney function decline was defined as a decrease in eGFR ≥3 mL/min/1.73 m²/year, and ΔeGFR represented the difference between baseline and endpoint eGFR. Multivariate logistic regression models and linear regression models were employed to evaluate the association between PEF and the risk of rapid eGFR decline, as well as the correlation between PEF and ΔeGFR.ResultsA total of 6159 participants were included, with 1157 (18.78%) individuals experiencing a rapid decline in eGFR. After adjusting for potential covariates, higher baseline PEF (Quartile 4 vs Quartile 1, OR=0.95, 95% CI 0.92 to 0.98) and elevated PEF % predicted (OR=0.96, 95% CI 0.94 to 0.99) were found to be associated with a lower risk of rapid eGFR decline. ΔeGFR decreased by 0.217 and 0.124 mL/min/1.73 m² for every 1 L/s increase in baseline PEF (β (95% CI): −0.217 (−0.393 to –0.042)) and 10% increase in PEF % predicted (β (95% CI): −0.124 (−0.237 to –0.011)), respectively. During the follow-up period, ΔeGFR decreased as PEF increased over time among participants in Quartile 1 (β per 1 L/s increase in ΔPEF=−0.581, 95% CI −1.003 to –0.158; β per 10% increase in ΔPEF % predicted=−0.279, 95% CI −0.515 to –0.043).ConclusionsHigher PEF was associated with a slower longitudinal eGFR decline in middle-aged and older adults.
Run, walk, cheer or volunteer: a patient and public involvement survey
Authors: Ross Alexandra , Gunasekera Roshan , Rowley Deborah 
Published: February 2024

BackgroundChildren with chronic diseases have been reported to participate in less regular physical activity (PA) than peers without chronic diseases; and less than recommended in guidelines. Sheffield Children’s Foundation Trust (SCFT) is an Active Hospitals pilot site, exploring options to facilitate PA for all children. One option is collaboration with Junior Parkrun: a free, weekly 2 km running event for children. The team investigated whether Junior Parkrun was of interest to guardians of children attending SCFT to increase PA.AimsThis patient and public involvement survey assessed perceptions of PA for children attending SCFT according to their accompanying guardians. This will inform a possible collaboration between SCFT and Junior Parkrun.MethodsA three-part, 14-question survey was developed, including demographics (age, ethnicity, postcode); perceptions of PA (barriers and facilitators); PA behaviours self-reported on Likert scales; and perceptions of Junior Parkrun. Guardians were asked whether they and their child would be interested in attending Junior Parkrun with SCFT staff support. This was distributed to guardians of children attending outpatient appointments.Results126 guardians responded. The average age of child was 10 years 10 months. 29.1% of guardians supported daily PA for their child. Almost half of respondents reported their child would be interested in attending Junior Parkrun. Of those not interested, the most common reason was travel.ConclusionThe findings highlighted PA barriers perceived by guardians, and identified that almost half of respondents would be interested in attending Junior Parkrun. A collaboration between Junior Parkrun and SCFT could be explored.
Assisted deaths in Switzerland for UK residents: diagnoses and their implications for palliative medicine and assisted dying legislation
Authors: Brewer Colin , Hopwood Marie-Claire , Winyard Graham 
Published: February 2024

ObjectiveUK campaigners for a law permitting assisted dying (AD) restricted to those with a maximum life expectancy of 6 months claim that this would largely remove the need for UK residents to seek AD in Switzerland. We wanted to discover whether this prediction was correct.MethodsWe analysed the diagnoses of UK residents who had such deaths including, for the first time, data from all three of the main Swiss providers of AD to non-residents, comparing them with figures from Oregon, which has a 6-month restriction.ResultsOnly 22.7% of UK residents had cancer (Oregon 72.5%) while nearly half (49.6% and over half including dementias) had neurological conditions (Oregon 11.2%) and many with prognoses of much more than 6 months.ConclusionOverall, less than half would meet a 6-month prognosis criterion. This has significant implications for patients, palliative care clinicians and legislators.
The resilience of Tethyan planktonic and benthic calcifying algae to Early Cretaceous perturbations: comparison between the Valanginian Weissert Event and the Early Aptian Oceanic Anoxic Event 1a
Authors: Erba Elisabetta , Parente Mariano 
Published: February 2024

Abstract

During the Cretaceous, the Berriasian–Aptian interval witnessed a transition from a relatively cool climate with intermittent polar ice to a greenhouse state that persisted throughout the Late Cretaceous. These palaeoclimatic changes were associated with the construction of large igneous provinces (LIPs), which significantly perturbed the ocean–atmosphere system by introducing large amounts of CO
2
, trace metals and micronutrients, thereby impacting the biosphere. Our study focused on the Tethyan Ocean during the Early Cretaceous, examining the resilience of planktonic and shallow-water benthic calcifying algae to environmental changes. We observed their adaptation, recovery dynamics and the influence of palaeoCO
2
levels on their resilience. Calcification patterns of calcareous nannoplankton served as a proxy for ecological and engineering resilience. While calcareous nannoplankton as a whole showed high resistance, individual taxa exhibited varying levels of resilience. Nannoconids, particularly narrow-canal ones, were highly sensitive and had low resistance. In contrast,
Watznaueria barnesiae
showed the least sensitivity and highest resistance, likely due to its adaptive strategies and long lifespan. Nannoplankton calcification recovery (engineering resilience) from the Weissert Event took
c.
3 million years. After the Early Aptian Oceanic Anoxic Event 1a (OAE1a), instead, nannoplankton did not return to pre-perturbation conditions. In shallow-water platforms, Dasycladales, aragonitic benthic calcifiers, exhibited lower resilience compared to nannofossils. They experienced a decline in species diversity across both the Weissert Event and the OAE 1a, which could indicate higher sensitivity to reduced carbonate saturation under high atmospheric
p
CO
2
conditions. After the Valanginian Weissert Event, Dasycladales were able to recover, albeit they show a much lower engineering resilience compared to nannoconids, as it took nearly 10 million years to revert to pre-disturbance diversity. The OAE 1a represented a more intense perturbation: the decrease of species diversity was much more drastic and permanent, and Dasycladales were unable to recover, losing their dominant role as carbonate platform biocalcifiers for the remainder of the Cretaceous. Our study provides an assessment of the resilience of Tethyan phytoplanktonic and shallow-water benthic calcifying algae to disturbances during the Early Cretaceous, with implications for tipping points associated with palaeoCO
2
levels. The differential responses in terms of timing and magnitude and the recovery dynamics contribute to the understanding of the potential impacts of current and future global changes on the resilience of marine ecosystems and the thresholds that may lead to ecological crises.
Image analysis of acoustic data and interpretation of rock stress orientations for geothermal exploration in Gothenburg borehole GE-1, SW Sweden
Authors: Ask Maria , Pierdominici Simona , Rosberg Jan-Erik 
Published: February 2024

Abstract
This study contributes to geothermal exploration in 1660–1520 Ma old, reworked bedrock in Sweden. Our primary objectives are to constrain the orientation of horizontal stresses, and to discuss implications for geothermal exploration. High-resolution acoustic televiewer image data reveal the downhole distribution of stress indicators (borehole breakouts, drilling-induced fractures and petal centreline fractures) and pre-existing structures (natural fractures, foliation). About 135 m of stress indicators are measured from 0.2–1.0 km. The results suggest a uniform NNW–SSE mean maximum horizontal stress orientation. A total of 1525 pre-existing structures (natural fractures, foliation) are mapped in borehole GE-1. The prevailing stress regime controls whether natural fractures and foliation are well-oriented for stimulation. For strike-slip and normal faulting stress regimes, well-oriented fractures steeply dip towards the WSW. For a reverse faulting stress regime, shallow dipping fractures are well-oriented for stimulation. The downhole distribution of stress indicators and other stress measurements in the region and other parts of Fennoscandia tentatively suggest a strike-slip stress regime, but additional studies are needed to constrain the complete stress field at study depth and towards engineered geothermal systems reservoir target depths.
Our secondary objective is to highlight that interpretation of high-resolution acoustic data, particularly in metamorphic crystalline rocks, is subjective and that more guidelines for data interpretation are needed. The interactive interpretation of the images is based on visual analyses of complex pre-existing structures and stress indicators with highly variable shapes. The application of three methods for data analyses in the GE-1 borehole proposes that drilling-induced fractures are little influenced by the method applied. Interpretations on individual borehole breakout azimuths may, however, result in over 10° differences in orientation.
Systematic Characterization of p53-Regulated Long Noncoding RNAs across Human Cancers Reveals Remarkable Heterogeneity among Different Tumor Types
Authors: Regunath Kausik , Fomin Vitalay , Liu Zhaoqi , Wang Pingzhang , Hoque Mainul , Tian Bin , Rabadan Raul , Prives Carol 
Published: February 2024

Abstract

The p53 tumor suppressor protein, a sequence-specific DNA binding transcription factor, regulates the expression of a large number of genes, in response to various forms of cellular stress. Although the protein coding target genes of p53 have been well studied, less is known about its role in regulating long noncoding genes and their functional relevance to cancer. Here we report the genome-wide identification of a large set (&gt;1,000) of long noncoding RNAs (lncRNA), which are putative p53 targets in a colon cancer cell line and in human patient datasets from five different common types of cancer. These lncRNAs have not been annotated by other studies of normal unstressed systems. In the colon cancer cell line, a high proportion of these lncRNAs are uniquely induced by different chemotherapeutic agents that activate p53, whereas others are induced by more than one agent tested. Further, subsets of these lncRNAs independently predict overall and disease-free survival of patients across the five different common cancer types. Interestingly, both genetic alterations and patient survival associated with different lncRNAs are unique to each cancer tested, indicating extraordinary tissue-specific variability in the p53 noncoding response. The newly identified noncoding p53 target genes have allowed us to construct a classifier for tumor diagnosis and prognosis.

Implications:
Our results not only identify myriad p53-regulated long noncoding (lncRNA), they also reveal marked drug-induced, as well as tissue- and tumor-specific heterogeneity in these putative p53 targets and our findings have enabled the construction of robust classifiers for diagnosis and prognosis.
Early Changes in Tumor-Naive Cell-Free Methylomes and Fragmentomes Predict Outcomes in Pembrolizumab-Treated Solid Tumors
Authors: Stutheit-Zhao Eric Y. , Sanz-Garcia Enrique , Liu Zhihui (Amy) , Wong Derek , Marsh Kayla , Abdul Razak Albiruni R. , Spreafico Anna , Bedard Philippe L. , Hansen Aaron R. , Lheureux Stephanie , Torti Dax , Lam Bernard , Yang Shih Yu Cindy , Burgener Justin , Luo Ping , Zeng Yong , Cheng Nicholas , Awadalla Philip , Bratman Scott V. , Ohashi Pamela S. , Pugh Trevor J. , Siu Lillian L. 
Published: February 2024

Abstract

Early kinetics of circulating tumor DNA (ctDNA) in plasma predict response to pembrolizumab but typically requires sequencing of matched tumor tissue or fixed gene panels. We analyzed genome-wide methylation and fragment-length profiles using cell-free methylated DNA immunoprecipitation and sequencing (cfMeDIP-seq) in 204 plasma samples from 87 patients before and during treatment with pembrolizumab from a pan-cancer phase II investigator-initiated trial (INSPIRE). We trained a pan-cancer methylation signature using independent methylation array data from The Cancer Genome Atlas to quantify cancer-specific methylation (CSM) and fragment-length score (FLS) for each sample. CSM and FLS are strongly correlated with tumor-informed ctDNA levels. Early kinetics of CSM predict overall survival and progression-free survival, independently of tumor type, PD-L1, and tumor mutation burden. Early kinetics of FLS are associated with overall survival independently of CSM. Our tumor-naïve mutation-agnostic ctDNA approach integrating methylomics and fragmentomics could predict outcomes in patients treated with pembrolizumab.

Significance:
Analysis of methylation and fragment length in plasma using cfMeDIP-seq provides a tumor-naive approach to measure ctDNA with results comparable with a tumor-informed bespoke ctDNA. Early kinetics within the first weeks of treatment in methylation and fragment quantity can predict outcomes with pembrolizumab in patients with various advanced solid tumors.
This article is featured in Selected Articles from This Issue, p. 897