bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fleshing out the data: when epidemiological researchers engage with patients and carers. Learning lessons from a patient involvement activity
Authors: Morris Melanie , Alencar Yuki , Rachet Bernard , Stephens Richard , Coleman Michel P 
Published: September 2020

Patient and public involvement and engagement has become an essential element of health research, ensuring aims and outputs are worthwhile and relevant. However, research involving secondary data analyses does not present immediately obvious ways to involve patients and the public. Innovative approaches to ensure their involvement is meaningful and effective are required.The Cancer Survival Group cohosted a full-day meeting with the National Cancer Research Institute Consumer Forum—a group of patients and carers. This included the Forum’s ‘Dragons’ Den’: a small-group session in which their members provided insight, advice and ideas on current or planned research in the Cancer Survival Group.We investigated this activity as an example of effective patient involvement, with the aim of developing broad recommendations to improve epidemiological/quantitative research by involving patients and carers as directly as possible.In addition to quantitative data captured through evaluation forms completed after the event, we used semistructured interviews of a sample of participants to evaluate the effectiveness of the session and to learn lessons. The interviews were analysed to identify broad or recurrent themes and recommendations.Feedback was overwhelmingly positive, and some impacts on the research projects were identified. Interviewees commented on overall expectations and experiences, as well as specifics of room layout, timing of the session, composition of groups, effectiveness of the facilitation and content of discussions.We present a summary of our findings as a guide for other researchers, including recommendations for improvement gleaned from the interviews. The value to researchers of hosting and participating in such activities was clear. We developed recommendations that should help to improve future events for ourselves and for others who wish to conduct similar activities, which in turn may lead to more concrete benefits for research and patients.
Healthcare utilisation and expenditure patterns for cardio-metabolic diseases in South Asian cities: the CARRS Study
Authors: Gupta Priti , Singh Kalpana , Shivashankar Roopa , Singh Kavita , Vamadevan Ajay , Mohan V , Kadir Muhammad Masood , Tandon Nikhil , Narayan K M , Prabhakaran Dorairaj , Ali Mohammed K 
Published: September 2020

ObjectiveTo estimate average annual expenditures per person, total economic burden and distress health financing associated with the treatment of five cardio-metabolic diseases (CMDs—hypertension, diabetes, heart disease (angina, myocardial infarction and heart failure), stroke and chronic kidney disease) in three metropolitan cities in South Asia.DesignCross-sectional surveys.SettingWe analysed community-based baseline data from the Centre for cArdio-metabolic Risk Reduction in South Asia (CARRS) Study collected in 2010–2011 representing Chennai and New Delhi (India), and Karachi (Pakistan).ParticipantsWe used data from non-pregnant adults (≥20 years) from the aforementioned cities that responded to a cost-of-illness questionnaire. We estimated health utilisation and expenditures among those reporting taking treatment(s) for the aforementioned CMDs in the last 1 year. We converted all costs to International Dollars (Int$ 2011) and inflated to 2018 values. The annual costs per person were stratified by city, sociodemographic characteristics, contributor of costs and financing methods. The total economic burden of CMDs for each city was projected using age-standardised prevalence and per-person costs of diseases reported in CARRS, applying these to population data from the most recent census. We also calculated distress financing (DF) as having to borrow or sell assets to pay for CMD treatment and identified sociodemographic groups at most risk of DF using multiple regression.ResultsOf 16 287 CARRS participants, 2883 (17.7%) reported receiving treatment for CMDs. The total annual expenditures reported per patient for CMDs ranged from Int$358 to Int$2425. Medications constituted 46% of total direct expenditures and out-of-pocket (OOP) expenditures accounted for nearly 80% of financing these health expenditures. Total economic burdens of CMDs were Int$0.42 billion, Int$3.4 billion and Int$1.4 billion in Chennai, New Delhi and Karachi, respectively. Overall, 36.1% experienced DF, and women (OR=4.4), unemployed (OR=10.7) and uninsured (OR=8.1) adults experienced higher odds of DF.ConclusionCMDs are associated with large economic burdens in South Asia. Due to most payments coming from OOP expenditures and limited insurance, the odds of DF are high.
Protocol for development, calibration and validation of the Patient-Reported Inventory of Self-Management of Chronic Conditions (PRISM-CC)
Authors: Packer Tanya , Kephart George , Audulv Åsa , Keddy America , Warner Grace , Peacock Kylie , Sampalli Tara 
Published: September 2020

IntroductionAssessing and measuring patients’ chronic condition self-management needs are critical to quality health care and to related research. One in three adults around the world live with multiple chronic conditions. While many patient-reported measures of self-management have been developed, none has emerged as the gold standard, and all have one or more of the following limitations: (1) they fail to measure the different domains of self-management important to patients, (2) they lack sufficient specificity to support patient-centred care or identify the specific components of self-management interventions that work and/or (3) they lack suitability for patients with multiple chronic conditions.Methods and analysisThe Patient-Reported Inventory of Self-Management of Chronic Conditions (PRISM-CC) is being developed to overcome these shortcomings. It will measure respondents’ perceived success (or difficulty) in self-managing seven domains important to patients. The protocol has three phases. Phase 1 is conceptual model development and item generation. Phase 2 is assessment of the relevance and understanding of items by people with chronic conditions. Phase 3 is item analysis, dimensionality assessment, scaling and preliminary validation of the PRISM-CC using an online survey of people with chronic conditions (n~750). The expected completion date is early 2021.Ethics and disseminationThis study will adhere to the Canadian Tri-Council Policy Statement on Ethical Conduct for Research Involving Humans. Ethics approval for all phases has been obtained from the Nova Scotia Health Authority Research Ethics Board. Once completed, the PRISM-CC will be made available for research and healthcare at minimal to no cost.
Nature of adverse events with opioids in hospitalised patients: a post-hoc analysis of three patient record review studies
Authors: Schutijser Bernadette Clara Francisca Maria , Jongerden Irene , Klopotowska Joanna Ewa , Moesker Marco , Langelaan Maaike , Wagner Cordula , de Bruijne Martine 
Published: September 2020

ObjectiveOpioids are increasingly prescribed and frequently involved in adverse drug events (ADEs). The underlying nature of opioid-related ADEs (ORADEs) is however understudied. This hampers our understanding of risks related to opioid use during hospitalisation and when designing interventions. Therefore, we provided a description of the nature of ORADEs.DesignA post-hoc analysis of data collected during three retrospective patient record review studies (in 2008, 2011/2012 and 2015/2016).SettingThe three record review studies were conducted in 32 Dutch hospitals.ParticipantsA total of 10 917 patient records were assessed by trained nurses and physicians.Outcome measuresPer identified ORADE, we described preventability, type of medication error, attributable factors and type of opioids involved. Moreover, the characteristics of preventable and non-preventable ORADEs were compared to identify risk factors.ResultsOut of 10 917 patient records, 357 ADEs were identified, of which 28 (8%) involved opioids. Eleven ORADEs were assessed as preventable. Of these, 10 were caused by dosing errors and 4 probably contributed to patients’ death. Attributable factors identified were mainly on patient and organisational levels. Morphine and oxycodone were the most frequently involved opioids. The risk for ORADEs was higher in elderly patients.ConclusionsOnly 8% of ADEs identified in our sample were related to opioids. Although the frequency is low, the risk of serious consequences is high. We recommend to use our findings to increase awareness among physicians and nurses. Future interventions should focus on safe dosing of opioids when prescribing and administering, especially in elderly patients.
Topical chlorhexidine 0.2% versus topical natamycin 5% for fungal keratitis in Nepal: rationale and design of a randomised controlled non-inferiority trial
Authors: Hoffman Jeremy John , Yadav Reena , Das Sanyam Sandip , Chaudhary Pankaj , Roshan Abhishek , Singh Sanjay Kumar , Arunga Simon , Matayan Einoti , Macleod David , Weiss Helen Anne , Leck Astrid , Hu Victor , Burton Matthew J 
Published: September 2020

IntroductionFungal infections of the cornea, fungal keratitis (FK), are challenging to treat. Current topical antifungals are not always effective and are often unavailable, particularly in low-income and middle-income countries where most cases occur. Topical natamycin 5% is usually first-line treatment, however, even when treated intensively, infections may progress to perforation of the eye in around a quarter of cases. Alternative antifungal medications are needed to treat this blinding disease.Chlorhexidine is an antiseptic agent with antibacterial and antifungal properties. Previous pilot studies suggest that topical chlorhexidine 0.2% compares favourably with topical natamycin. Full-scale randomised controlled trials (RCTs) of topical chlorhexidine 0.2% are warranted to answer this question definitively.Methods and analysisWe will test the hypothesis that topical chlorhexidine 0.2% is non-inferior to topical natamycin 5% in a two-arm, single-masked RCT. Participants are adults with FK presenting to a tertiary ophthalmic hospital in Nepal. Baseline assessment includes history, examination, photography, in vivo confocal microscopy and cornea scrapes for microbiology. Participants will be randomised to alternative topical antifungal treatments (topical chlorhexidine 0.2% and topical natamycin 5%; 1:1 ratio, 2–6 random block size). Patients are reviewed at day 2, day 7 (with reculture), day 14, day 21, month 2 and month 3. The primary outcome is the best spectacle corrected visual acuity (BSCVA) at 3 months. Primary analysis (intention to treat) will be by linear regression, with treatment arm and baseline BSCVA prespecified covariates. Secondary outcomes include epithelial healing time, scar/infiltrate size, ulcer depth, hypopyon size, perforation and/or therapeutic penetrating keratoplasty (corneal transplant), positive reculture rate (day 7) and quality of life (EuroQol-5 dimensions, WHO/PBD-VF20, WHOQOL-BREF).Ethics and disseminationThe Nepal Health Research Council, the Nepal Department of Drug Administration and the London School of Hygiene and Tropical Medicine ethics committee have approved the trial. The results will be presented at local and international meetings and submitted to peer-reviewed journals for publication.Trial registration numberISRCTN14332621; pre-results.
Management of sleep apnoea syndrome (SAS) in patients with vasovagal syncope (VVS): a protocol for the VVS-SAS cohort study
Authors: Puel Vincent , Godard Isabelle , Papaioannou Georgios , Gosse Philippe , Pepin Jean Louis , Thoin Fabrice , Deharo Jean Claude , Roche Frederic , Zarqane Naïma , Gagnadoux Frédéric , Suehs Carey Meredith , Molinari Nicolas 
Published: September 2020

IntroductionRecurrent vasovagal syncope (VVS) is associated with decreased quality-of-life and frequent use of emergency services. The evidence base for causality, diagnostic procedures and potential VVS treatments is poor. Scattered observations in the literature suggest a link between respiratory disturbances during sleep and VVS. Empirical observations lead us to further hypothesise that the appropriate management of sleep apnoea syndrome (SAS) may help resolve comorbid recurrent VVS in certain patients. We therefore designed this pilot study to provide a framework for the observation of changes in outcomes accompanying the deployment of SAS treatments in patients with VVS.Methods and analysisThis is a multicentre, registry-based study whose primary objective is to evaluate the effect of SAS management on the number of syncope/presyncope episodes in a population suffering from both VVS and SAS. To this effect, syncope rates prior to the treatment of SAS will be compared with those occurring after the initiation of the latter. In addition, yearly assessments will collect data for echocardiography, polysomnography, Holter monitoring, table tilt tests, multiple sleep latency tests, SAS management parameters and questionnaires describing fatigue, depression and quality-of-life. Sixty patients will be included with a minimum follow-up period of 12 months. The primary analysis will use comparisons of centrality for paired data to describe the changes in syncope rates before versus after the initiation of SAS management. Longitudinal data will be analysed using mixed models with patients set as a random effect. Subgroup analyses will be performed for SAS-treatment adherence and efficacy.Ethics and disseminationThe VVS-SAS registry was approved by an ethics committee (Comité pour la Protection des Personnes Ile-de-France VI, Reference number CPP/2-18) in accordance with French law. The princeps publication will present before–after SAS management results and longitudinal analyses.Trial registration numberNCT04294524. Pre-results.
Impact of preoperative HbA1c on postoperative complications after elective major abdominal surgery: a systematic review protocol
Authors: Wong Joanna Kae Ling , Ke Yuhe , Ong Yi Jing , Li Hui Hua , Abdullah Hairil Rizal 
Published: September 2020

IntroductionDiabetes has an increasing worldwide prevalence. It is known to be a predisposing factor for postoperative complications. Preoperative glycaemic control strategies should be pursued as glycaemic control could serve as a modifiable risk factor. Glycated haemoglobin (HbA1c), a marker of 3-month average glycaemic control, has been shown in meta-analyses to predict postoperative complications in cardiothoracic, bariatric and orthopaedic surgery. However, there is no meta-analysis in the major abdominal surgery population, in whom morbidity may be higher due to the nature of the surgery. Understanding the association between HbA1c and postoperative complications could help in preoperative risk prognostication, counselling and glycaemic target selection. The aim of this systematic review and meta-analysis is to evaluate all evidence on the association between preoperative HbA1c and postoperative complications in elective major abdominal surgery, and to investigate the threshold HbA1c level before postoperative complication rates increase.Methods and analysisThis review will be performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols guidelines. PubMed, Embase, Cochrane Central Register of Controlled Trials, Google Scholar and China National Knowledge Infrastructure will be searched for all original studies. Study selection, data extraction, risk of bias and quality assessment will be conducted by two independent reviewers. The primary outcome is the association between preoperative HbA1c and major postoperative complications (Clavien Dindo 3–5), and the secondary outcome is the association between HbA1c and overall postoperative complications. Data management and synthesis will be performed using Microsoft Excel and Stata to derive pool estimates.Ethics and disseminationNo ethics approval is required as only secondary data will be used. Findings will be disseminated through peer-reviewed journals and conference presentations.PROSPERO registration numberCRD42020167347.
Determining the level of data sharing, and number of publications, from research databases that have been given a favourable opinion by UK research ethics committees
Authors: Trace Samantha , Bracher Mike , Kolstoe Simon E 
Published: September 2020

ObjectiveTo determine data sharing and number of publications coming from research databases that have been given a favourable opinion by UK National Health Service (NHS) Research Ethics Committees (RECs).DesignCohort study.Inclusion criteria & settingAll research databases listed on the UK Health Research Authority’s Assessment Review Portal (HARP) that had received a favourable ethics opinion as of January 2018.Main outcome measuresPublications and data access requests are either listed on HARP or notified through subsequent email correspondence.ResultsOut of 354 eligible databases, 34% had granted access requests and 40% had produced at least one peer-reviewed paper or conference abstract/talk. We could not establish contact with 9% of databases, and 19% reported no access requests or publications. Only 9% of databases were up to date with all annual reports. Email responses from database owners showed a range of attitudes towards data sharing.ConclusionLess than half of research databases that have received a favourable opinion from NHS research ethics committees share their data and produce publications. There is also considerable variability in the operation of research databases and understanding of the purpose of research databases. This work was hampered by incomplete records due mainly to researchers not submitting annual reports.
Host genetics and tumor environment determine the functional impact of neutrophils in mouse tumor models
Authors: van Elsas Marit , Kleinovink Jan Willem , Moerland Matthijs , Feiss Gary , Beyrend Guillaume , Arens Ramon , Mei Hailiang , Nibbering Peter H , Jirka Silvana M , van Hall Thorbald , van der Burg Sjoerd H 
Published: September 2020

BackgroundNeutrophils have been reported to have protumor, antitumor or neutral effects in cancer progression. The underlying causes for this functional variability are not clear.MethodsWe studied the role of neutrophils in six different mouse tumor models by intratumoral injection of antimicrobial peptides or vaccination. Changes in systemic and intratumoral immune cells were analyzed by flow-cytometry and mass-cytometry. The role of neutrophils was studied by antibody-mediated neutrophil depletion. Neutrophils from different mouse strains were compared by RNA sequencing.ResultsThe antimicrobial peptide Omiganan reduced the growth of TC-1 tumors in BL/6 mice and CT26 tumors in BALB/c mice. No significant effects were observed in B16F10, MC38 and 4T1 tumors. Growth delay was associated with increased abundance of neutrophils in TC-1 but not CT26 tumors. Systemic neutrophil depletion abrogated Omiganan efficacy in TC-1 but further reduced growth of CT26, indicating that neutrophils were required for the antitumor effect in TC-1 but suppressed tumor control in CT26. Neutrophils were also required for a therapeutic vaccine-induced T-cell mediated control of RMA tumors in BL/6 mice. Clearly, the circulating and intratumoral neutrophils differed in the expression of Ly6G and CD62L, between TC-1 and CT26 and between blood neutrophils of tumor-naïve BL/6 and BALB/c mice. RNA-sequencing revealed that neutrophils from BL/6 mice but not BALB/c mice displayed a robust profile of immune activation, matching their opposing roles in TC-1 and RMA versus CT26.ConclusionsNeutrophil functionality differs strongly between mouse strains and tumor types, with consequences for tumor progression and therapy.
Dry matter content association with time of on-tree maturation, quality at harvest, and changes in quality after controlled atmosphere storage for ‘Royal Gala’ apples
Authors: Toivonen Peter M.A. , Lannard Brenda 
Published: September 2020

On-tree maturation was monitored in a commercial ‘Royal Gala’ apple orchard in two separate years (2016 and 2017) and was found to advance more quickly in 2017 as compared with 2016. Dry matter was predicted using a handheld infrared spectrometer and dry matter content (relative to fresh weight) was 18.2% in 2016 and 14.7% in 2017. The lower average dry matter content in 2017 was hypothesized to be associated with accelerated maturation on the tree. Apples were harvested for storage testing, in both years, at a target maturity at which internal ethylene levels had reached approximately 1 μL·L−1, starch clearing index was between 2 and 4 on the Cornell starch chart, and IAD value (measure of relative chlorophyll content in the peel) was approximately 0.5. Consequent, instrumentally measured flesh quality changes were monitored after ultra-low oxygen, controlled atmosphere (CA) storage (0.7 kPa O2 + 1.0 kPa CO2) at 0.5 °C for 3 and 6 mo. The firmness, soluble solids, and titratable acidity were much higher in the apples from the 2016 harvest. While these quality measures declined during 3 and 6 mo of storage, they were consistently higher in the apples from the 2016 season. These results show that when dry matter contents were higher for ‘Royal Gala’ apples from this orchard, harvest maturity was delayed and fruit were much firmer and had higher contents of soluble solids and somewhat higher titratable acidity at harvest and after ultra-low oxygen CA storage for up to 6 mo.
Acute Statin Treatment Improves Antibody Accumulation in EGFR- and PSMA-Expressing Tumors
Authors: Pereira Patrícia M.R. , Mandleywala Komal , Ragupathi Ashwin , Lewis Jason S. 
Published: September 2020

Abstract

Purpose:
Statins are cholesterol-depleting drugs used to treat patients with hypercholesterolemia. Preclinically, statins disrupt trafficking of receptors present at the cell membrane. Membrane receptors, defined as tumor biomarkers and therapeutic targets, are often internalized by an endocytic pathway. Indeed, receptor endocytosis and recycling are dynamic mechanisms that often affect receptor density at the cell surface. In therapies using monoclonal antibodies (mAb), a downregulation in receptor density at the cell surface decreases antibody binding to the extracellular domain of the membrane receptor. Here, we determined the potential of lovastatin, simvastatin, and rosuvastatin in preclinically modulating epidermal growth factor receptor (EGFR) and prostate-specific membrane antigen (PSMA) receptor density at the tumor cell surface.

Experimental Design:
Small-animal PET was used to study the binding of 89Zr-labeled antibodies in ectopic xenografts. Ex vivo analyses were performed to determine changes in endocytic proteins, EGFR, and PSMA surface levels.

Results:
Acute statin treatment using lovastatin, simvastatin, or rosuvastatin enhanced tumors' avidity for the mAbs panitumumab, cetuximab, and huJ591. Statins temporarily modulated caveolin-1, cavin-1, endophilin, clathrin, and dynamin proteins in EGFR- and PSMA-overexpressing xenografts.

Conclusions:
These data show the potential of statins as pharmacologic modulators of endocytic proteins for improved tumors' accumulation of mAbs. The translational significance of these findings lies in the potential of statins to temporarily modulate the heterogeneous presence of receptors at the cell membrane, a characteristic often associated with poor response in tumors to therapeutic antibodies.
Next-generation Sequencing of Cerebrospinal Fluid: How Can a Liquid be Like a Solid?
Authors: Marmarelis Melina E. , Bauml Joshua M. 
Published: September 2020

Abstract
The APOLLO investigators showed that next-generation sequencing of cerebrospinal fluid can reveal molecular alterations—how should this affect our management approach?
See related article by Xing et al., p. 6168