bluuebunny/crossref_metadata_2025_split huggingface dataset:
Case-ascertainment of acute myocardial infarction hospitalizations in cancer patients: a cohort study using English linked electronic health data
Authors: Coles Briana , Teece Lucy , Weston Clive , de Belder Mark A , Oliver-Williams Clare , Welch Catherine A , Rutherford Mark J , Lambert Paul C , Bidulka Patrick , Paley Lizz , Nitsch Dorothea , Deanfield John , Peake Mick D , Adlam David , Sweeting Michael J 
Published: June 2021

Abstract

Aims
To assess the recording and accuracy of acute myocardial infarction (AMI) hospital admissions between two electronic health record databases within an English cancer population over time and understand the factors that affect case-ascertainment.

Methods and results
We identified 112 502 hospital admissions for AMI in England 2010–2017 from the Myocardial Ischaemia National Audit Project (MINAP) disease registry and hospital episode statistics (HES) for 95 509 patients with a previous cancer diagnosis up to 15 years prior to admission. Cancer diagnoses were identified from the National Cancer Registration Dataset (NCRD). We calculated the percentage of AMI admissions captured by each source and examined patient characteristics associated with source of ascertainment. Survival analysis assessed whether differences in survival between case-ascertainment sources could be explained by patient characteristics. A total of 57 265 (50.9%) AMI admissions in patients with a prior diagnosis of cancer were captured in both MINAP and HES. Patients captured in both sources were younger, more likely to have ST-segment elevation myocardial infarction and had better prognosis, with lower mortality rates up to 9 years after AMI admission compared with patients captured in only one source. The percentage of admissions captured in both data sources improved over time. Cancer characteristics (site, stage, and grade) had little effect on how AMI was captured.

Conclusion
MINAP and HES define different populations of patients with AMI. However, cancer characteristics do not substantially impact on case-ascertainment. These findings support a strategy of using multiple linked data sources for observational cardio-oncological research into AMI.
Early invasive coronary angiography and acute ischaemic heart failure outcomes
Authors: Kosyakovsky Leah B , Austin Peter C , Ross Heather J , Wang Xuesong , Abdel-Qadir Husam , Goodman Shaun G , Farkouh Michael E , Croxford Ruth , Lawler Patrick R , Spertus John A , Lee Douglas S 
Published: June 2021

Abstract

Aims
While myocardial ischaemia plays a major role in the pathogenesis of heart failure (HF), the indications for coronary angiography during acute HF are not established. We determined the association of early coronary angiography during acute HF hospitalization with 2-year mortality, cardiovascular death, HF readmissions, and coronary revascularization.

Methods and results
In a two-stage sampling process, we identified acute HF patients who presented to 70 emergency departments in Ontario (April 2010 to March 2013) and determined whether they underwent early coronary angiography within 14 days after presentation using administrative databases. After clinical record review, we defined a cohort with acute ischaemic HF as patients with at least one factor suggesting underlying ischaemic heart disease, including previous myocardial infarction, troponin elevation, or angina on presentation. We oversampled patients undergoing angiography. We used inverse-probability-of-treatment weighting (IPTW) to adjust for baseline differences. Of 7239 patients with acute HF, 2994 met inclusion criteria [median age 75 (interquartile range 65–83) years; 40.9% women]. Early angiography was performed in 1567 patients (52.3%) and was associated with lower all-cause mortality [hazard ratio (HR) 0.74, 95% confidence interval (CI) 0.61–0.90, P = 0.002], cardiovascular death (HR 0.72, 95% CI 0.56–0.93, P = 0.012), and HF readmissions (HR 0.84, 95% CI 0.71–0.99, P = 0.042) after IPTW. Those undergoing early angiography experienced higher rates of percutaneous coronary intervention (HR 2.58, 95% CI 1.73–3.86, P &lt; 0.001) and coronary artery bypass grafting (HR 2.94, 95% CI 1.75–4.93, P &lt; 0.001) within 2 years.

Conclusions
Early coronary angiography was associated with lower all-cause mortality, cardiovascular death, HF readmissions, and higher rates of coronary revascularization in acute HF patients with possible ischaemia.
Identity of Applicants for Priority Rights and the EPO’s CRISPR-Cas/Broad Institute Decision T 0844/18 ‒ Scope of the EPO’s ‘Formal Review’ to Establish Identity of the Holder of the Priority Right
Authors: Haedicke Maximilian 
Published: June 2021

Abstract
The Technical Board of Appeal 3.3.08 (hereinafter ‘the Board’) has handed down the much-awaited written decision regarding the denial of the CRISPR/Cas9 patent EP2771468. The Board did not acknowledge the patentee’s claim to priority from a provisional US application naming more applicants than the subsequent Patent Cooperation Treaty (PCT) application from which the European patent was derived. The Board considered the priority claim invalid because there was no identity between the applicants of the prior and subsequent application. This article does not second-guess the ‘all applicants’ approach as confirmed by the Board, but considers the consequences of the decision for the claiming of priority by the ‘same applicants’.
How do Polish pharmacy staff evaluate own qualifications, competences, relevance, motivation, effectiveness in health promotion?
Authors: Raczkiewicz Dorota , Sarecka-Hujar Beata , Pawełczak-Barszczowska Adrianna , Bojar Iwona 
Published: June 2021

Summary
Health promotion programmes are complex and need to engage all health care specialists, including pharmacists. Pharmacies are considered as a potentially ideal place for health promotion and education. To evaluate own qualifications, competences, relevance, motivation and effectiveness of Polish pharmacy staff with regard to health-related information provided to patients, which contributes to health promotion. 308 pharmacy staff from Lublin (Poland) were surveyed with a questionnaire prepared by the researchers and piloted previously. It consisted of 5 domains: qualifications, competences, relevance, motivation, and effectiveness of health promotion. Items in each domain were scored by respondents in 1 − 10 scale where 1 is ‘very low’ and 10 is ‘very high’. Pharmacy staff rated the relevance of health promotion the highest, while the lowest—own competences and effectiveness in health promotion. Female pharmacy staff assessed the relevance of health promotion significantly higher than males (7.1 vs. 6.1, p = 0.005). Higher self-assessments of qualifications, competences, relevance, motivation and effectiveness in health promotion were provided by: the youngest pharmacy staff, those with a short period of employment, and pharmacy staff working in pharmacies employing up to 3 persons. Qualification and competences in health promotion were assessed higher by pharmacy technicians and masters of pharmacy with post-graduate studies or professional specialization, or Ph.D. than by masters of pharmacy. Relevance and effectiveness in health promotion were evaluated higher by pharmacy staff in pharmacies serving more than 100 customers daily. There is a need to improve qualifications, competences, relevance, motivation and effectiveness in health promotion conducted by Polish pharmacy staff.
The Swedish Health Promoting Healthcare network and the built environment
Authors: Miedema Elke , Lindahl Göran , Elf Marie 
Published: June 2021

Abstract
The Health Promoting Hospitals (HPH) networks, founded by the World Health Organisation, support the introduction of health promotion in healthcare. This development involves the creation of a health promoting built environment. However, few studies have explored the HPH in relation to the built environments, and it is unclear how HPH-networks incorporate the built environment in their work. The study therefore examined the Swedish HPH-Network in relation to the built environment. The mixed-method study included data from (i) key online material from the Swedish network, (ii) a survey with open-ended questions of representatives of the networks’ workgroups and (iii) semi-structured interviews with the built environment workgroup. The study showed that the built environment is unevenly and incoherently incorporated in the network. Moreover, there is more attention for healing and healthy rather than health-promotive strategies, indicating a knowledge gap. Descriptions of the health promoting built environment are diverse, and address design features, design strategies or indicate places for health promotion interventions. The descriptions of the built environment are combined with various HPH goals and population groups. To utilize the built environment as a resource for HPHs, the networks should consider incorporating the built environment in documents and action plans at all organizational levels.
Is the quality-of-life improvement after transcatheter aortic valve implantation equivalent to that achieved by surgical aortic valve replacement?
Authors: Monteagudo-Vela Maria , Panoulas Vasileios , Kourliouros Antonios , Krasopoulos George 
Published: June 2021

Summary
A best evidence topic in cardiac surgery was written according to a structured protocol. The question addressed was ‘is the quality-of-life (QoL) improvement after transcatheter aortic valve implantation (TAVI) equivalent to that achieved by surgical aortic valve replacement (sAVR)?’ Literature search revealed 189 papers with reference to QoL after TAVI, of which 7 represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers were tabulated. QoL plays a crucial role in the decision-making process for procedures such as TAVI and sAVR. Current evidence included and analysed in this review have shown a clear improvement in QoL after both TAVI and sAVR. TAVI offers a rapid improvement of QoL, evident within the first 30 days. There is no difference in QoL at 2- and 5-year follow-up between TAVI and sAVR. There are currently paucity of data on long-term QoL and the potential impact of structural valve degeneration following TAVI.
Accelerating the Evolution of Severe Acute Respiratory Syndrome Coronavirus 2: A Risk of Combining Dexamethasone and Tocilizumab for Severe Coronavirus Disease 2019
Authors: Koeckerling David , Barker Joseph 
Published: June 2021

Abstract
Emerging data from open-label randomized trials without placebo controls suggest potential mortality benefits for combining corticosteroids with the interleukin 6 receptor antagonist tocilizumab in severe coronavirus disease 2019. Conversely, dual immunomodulation may weaken antiviral responses and delay viral clearance, allowing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to expand its population and accrue genetic diversity within individual hosts. Generating a pool of hosts with genetically diverse viral populations while introducing new selective pressures in the form of vaccination-induced immunity could accelerate the process of antigenic drift in SARS-CoV-2. However, clinical trials to date have largely disregarded viral outcomes, and data on viral kinetics in response to immunomodulation are scarce. Coadministration of antiviral agents with immunomodulation could serve as a potential strategy to aid viral clearance and reduce the risk of genetic diversification.
Thirteen-Valent Pneumococcal Conjugate Vaccine–Induced Immunoglobulin G (IgG) Responses in Serum Associated With Serotype-Specific IgG in the Lung
Authors: Mitsi Elena , McLenaghan Daniella , Wolf Asia-Sophia , Jones Scott , Collins Andrea M , Hyder-Wright Angela D , Goldblatt David , Heyderman Robert S , Gordon Stephen B , Ferreira Daniela M 
Published: June 2021

Abstract
Pneumococcal conjugate vaccine (PCV) efficacy is lower for noninvasive pneumonia than invasive disease. In this study, participants were immunized with 13-valent PCV (PCV13) or hepatitis A vaccine (control). Bronchoalveolar lavage samples were taken between 2 and 6 months and serum at 4 and 7 weeks postvaccination. In the lung, anti-capsular immunoglobulin G (IgG) levels were higher in the PCV13 group compared to controls for all serotypes, except 3 and 6B. Systemically, IgG levels were elevated in the PCV13 group at 4 weeks for all serotypes, except serotype 3. IgG in bronchoalveolar lavage and serum positively correlated for nearly all serotypes. PCV13 shows poor immunogenicity to serotype 3, implying lack of protective efficacy.
Clinical Trials Registration. ISRCTN 45340436.
Intramuscular and subcutaneous administration of antiretroviral drugs, compared with oral, enhances delivery to lymphoid tissues in BALB/c mice
Authors: Dyavar Shetty Ravi , Kumar Sushil , Gautam Nagsen , Podany Anthony T , Winchester Lee C , Weinhold Jonathan A , Mykris Timothy M , Nallasamy Palanisamy , Alnouti Yazen , Fletcher Courtney V 
Published: June 2021

Abstract

Background
Multiple tissue reservoirs are established soon after HIV infection, and some tissues may also be pharmacological sanctuaries. Parenteral administration of antiretroviral (ARV) drugs for treatment and prevention of HIV infection is an active area of drug development. The influence of route of administration on ARV tissue pharmacokinetics is not known.

Objectives
To investigate ARV pharmacokinetics in lymphatic and select non-lymphatic tissues (e.g. brain and testes) after intramuscular and subcutaneous administration compared with oral in BALB/c mice.

Methods
Tissue concentrations of cobicistat, efavirenz, elvitegravir, maraviroc, rilpivirine, tenofovir alafenamide and tenofovir disoproxil fumarate were determined. The tissue penetration ratio (TPR) was the primary measure for comparison; a change in TPR arises from factors affecting tissue distribution controlling for changes in systemic bioavailability.

Results
Intramuscular and subcutaneous delivery increased TPRs in the lymph node and spleen for 27 of 28 (96%) drug administration events. Decreased TPRs, however, were found in some tissues such as the brain and testes.

Conclusions
These results demonstrate a change in route of drug administration from oral to intramuscular or subcutaneous can change tissue uptake. This has implications for HIV pharmacotherapy. For example, HIV persists in lymphoid tissues despite long-term oral ARV therapy, and low ARV concentrations have been found in lymphoid tissues. The improved ARV lymphatic tissue bioavailability with intramuscular and subcutaneous administration allows future studies to investigate these routes of drug administration as a therapeutic manoeuvre to limit viral persistence and eliminate viral sanctuaries in the lymphatic tissues, which is a prerequisite for eradication of HIV.
Expected clinical utility of automatable prediction models for improving palliative and end-of-life care outcomes: Toward routine decision analysis before implementation
Authors: Taseen Ryeyan , Ethier Jean-François 
Published: June 2021

Abstract

Objective
The study sought to evaluate the expected clinical utility of automatable prediction models for increasing goals-of-care discussions (GOCDs) among hospitalized patients at the end of life (EOL).

Materials and Methods
We built a decision model from the perspective of clinicians who aim to increase GOCDs at the EOL using an automated alert system. The alternative strategies were 4 prediction models—3 random forest models and the Modified Hospital One-year Mortality Risk model—to generate alerts for patients at a high risk of 1-year mortality. They were trained on admissions from 2011 to 2016 (70 788 patients) and tested with admissions from 2017-2018 (16 490 patients). GOCDs occurring in usual care were measured with code status orders. We calculated the expected risk difference (beneficial outcomes with alerts minus beneficial outcomes without alerts among those at the EOL), the number needed to benefit (number of alerts needed to increase benefit over usual care by 1 outcome), and the net benefit (benefit minus cost) of each strategy.

Results
Models had a C-statistic between 0.79 and 0.86. A code status order occurred during 2599 of 3773 (69%) hospitalizations at the EOL. At a risk threshold corresponding to an alert prevalence of 10%, the expected risk difference ranged from 5.4% to 10.7% and the number needed to benefit ranged from 5.4 to 10.9 alerts. Using revealed preferences, only 2 models improved net benefit over usual care. A random forest model with diagnostic predictors had the highest expected value, including in sensitivity analyses.

Discussion
Prediction models with acceptable predictive validity differed meaningfully in their ability to improve over usual decision making.

Conclusions
An evaluation of clinical utility, such as by using decision curve analysis, is recommended after validating a prediction model because metrics of model predictiveness, such as the C-statistic, are not informative of clinical value.
GWAS Identifies a Region Containing theSALL1Gene in Variation of Pigmentation Intensity Within the Chestnut Coat Color of Horses
Authors: Hammons Vada , Ribeiro Leticia , Munyard Kylie , Sadeghi Raheleh , Miller Donald , Antczak Douglas , Brooks Samantha A 
Published: June 2021

AbstractChestnut coat color in horses is determined by a missense mutation within the MC1R gene. However, the intensity of the chestnut color can vary widely within individuals possessing this genotype. Here, we investigated this variation using standardized photographs of 96 horses. Each horse was ranked lightest to darkest within the cohort for phenotype by 3 blinded observers. A genome-wide association study utilizing the relative shade ranking as the phenotype and using 268 487 single-nucleotide polymorphisms (SNPs) genotyped using the Affymetrix Equine 670k array identified a single significantly associated region on chromosome 3 (P = 2.934 × 10–8). Analysis of whole-genome sequences for horses spanning the diverse range of chestnut color identified candidate SNPs within the coding sequence of the only gene in the region: SALL1. The function of SALL1 is largely unknown, though it is predicted to interact with the Hermansky-Pudlak Syndrome type 1 (HPS1) protein, which causes partial albinism in humans. However, with only one study suggesting a circumstantial influence of the SALL1 protein on pigmentation, additional work is needed to confirm this new coat color locus in larger populations and investigate the function of this protein for impacts on equine health.
Debulking surgery for malignant tumors: the current status, evidence and future perspectives
Authors: Hishida Tomoyuki , Masai Kyohei , Kaseda Kaoru , Asakura Keisuke , Asamura Hisao 
Published: June 2021

Abstract
Debulking surgery, also called cytoreductive surgery, is a resection of the tumor as much as possible and an intended incomplete resection for unresectable malignant tumors. Since the most important principle in surgical oncology is complete R0 resection, debulking surgery goes against the basic principle and obscures the concept of operability. However, debulking surgery has been advocated for various types of advanced malignant tumors, including gynecological cancers, urological cancers, gastrointestinal cancers, breast cancers and other malignancies, with or without adjuvant therapy. Positive data from randomized trials have been shown in subsets of ovarian cancer, renal cell carcinoma, colorectal cancer and breast cancer. However, recent trials for renal cell carcinoma, colorectal cancer and breast cancer have tended to show controversial results, mainly according to the survival improvement of nonsurgical systemic therapy alone. On the other hand, debulking surgery still has a therapeutic role for slow-growing and borderline malignant tumors, such as pseudomyxoma peritonei and thymomas. The recent understanding of tumor heterogeneity and clonal evolution responsible for malignancy and drug resistance indicates that select patients may obtain prolonged survival by the synergistic effect of debulking surgery and novel systemic therapy. This review aimed to describe the current status and evidence of debulking surgery in a cross-organ manner and to discuss future perspectives in the current era with advances in systemic therapy.
Antibiotics Use and Subsequent Risk of Colorectal Cancer: A Swedish Nationwide Population-Based Study
Authors: Lu Sai San Moon , Mohammed Zahraa , Häggström Christel , Myte Robin , Lindquist Elisabeth , Gylfe Åsa , Van Guelpen Bethany , Harlid Sophia 
Published: June 2021

Abstract

Background
Antibiotics use may increase colorectal cancer (CRC) risk by altering the gut microbiota, with suggestive evidence reported. Our study aims to investigate antibiotics use in relation to subsequent CRC risk.

Methods
This is a nationwide, population-based study with a matched case-control design (first primary CRC cases and 5 matched, cancer-free controls). Complete-population data, extracted from Swedish national registers for the period 2005-2016, were used to calculate odds ratios and 95% confidence intervals.

Results
We included 40 545 CRC cases and 202 720 controls. Using the full dataset, we found a positive association between more frequent antibiotics use and CRC, excluding antibiotics prescribed within 2 years of diagnosis attenuated results toward the null. In site-specific analyses, excluding the 2-year washout, the positive association was confined to the proximal colon (adjusted odds ratio for very high use vs no use = 1.17, 95% confidence interval = 1.05 to 1.31). For rectal cancer, an inverse association, which appears to be driven by women, was observed. Quinolones and sulfonamides and/or trimethoprims were positively associated with proximal colon cancer, whereas a more general inverse association, across antibiotics classes, was observed for rectal cancer. We found no association between methenamine hippurate, a urinary tract antiseptic not affecting the gut microbiota, and CRC risk.

Conclusions
This register-based study covering the entire population of Sweden found a robust association between antibiotics use and higher risk of proximal colon cancer and an inverse association with rectal cancer in women. This study strengthens the evidence from previous investigations and adds important insight into site-specific colorectal carcinogenesis.