bluuebunny/crossref_metadata_2025_split huggingface dataset:
Interface leakage during neonatal CPAP treatment: a randomised, cross-over trial
Authors: Falk Markus , Gunnarsdottir Kolbrun , Baldursdottir Sonja , Donaldsson Snorri , Jonsson Baldvin , Drevhammar Thomas 
Published: May 2021

ObjectiveTo determine leakage for two neonatal continuous positive airway pressure (CPAP) interfaces and evaluate leak-corrective manoeuvres.DesignThe ToNIL (Trial of NCPAP Interface Leakage) study was a randomised, clinical, cross-over trial with data collection between August 2018 and October 2019. The primary outcome was blinded to the treating staff.SettingOne secondary, 8-bed neonatal intensive care unit (NICU) and three larger (>15 beds), academic NICU referral centres.PatientsNewborn infants with CPAP were screened (n=73), and those with stable spontaneous breathing, low oxygen requirement, postmenstrual age (PMA) over 28 weeks and no comorbidities were eligible. In total, 50 infants were included (median PMA 33 completed weeks).InterventionsLeakage was measured for both prongs and nasal mask, before and after leak-corrective manoeuvres. Interface application was performed in a randomised order by a nurse, blinded to the measured leakage.Main outcome measures30 s average leakage, measured in litres per minute (LPM).ResultsAnalyses showed a significantly lower leakage (mean difference 0.86 LPM, 95% CI 0.07 to 1.65) with prongs (median 2.01 LPM, IQR 1.00–2.80) than nasal mask (median 2.45 LPM, IQR 0.99–5.11). Leak-corrective manoeuvres reduced leakage significantly for both prongs (median 1.22 LPM, IQR 0.54–1.87) and nasal mask (median 2.35 LPM, IQR 0.76–4.75).ConclusionsLarge leakages were common for both interfaces, less with prongs. Simple care manoeuvres reduced leakage for both interfaces. This is the first report of absolute leakage for nasal interfaces and should encourage further studies on leakage during CPAP treatment.
Natural hazards, disasters and violence against women and girls: a global mixed-methods systematic review
Authors: Thurston Alyssa Mari , Stöckl Heidi , Ranganathan Meghna 
Published: May 2021

IntroductionDisasters triggered by climate and other natural hazards are increasing in frequency, severity and duration worldwide. Disasters disproportionately impact women and girls, with some evidence suggesting that violence against women and girls (VAWG) increases in disaster settings. Suggested risk factors for postdisaster VAWG include increased life stressors, failure of law enforcement, exposure to high-risk environments, exacerbation of existing gender inequalities and unequal social norms. We aim to systematically appraise the global literature on the association between disasters from natural hazards and VAWG.MethodsWe conducted a systematic review using the following databases: Embase, Global Health, Medline, PubMed and Social Policy and Practice and searched grey literature. We included quantitative, qualitative or mixed-methods studies published in English language that examined the association between disasters from natural hazards and VAWG. We summarised the findings using a narrative synthesis approach.ResultsOf 555 non-duplicate records, we included a total of 37 quantitative, qualitative and mixed-methods studies. Among the quantitative studies, eight studies found a positive association between disaster exposure and increased VAWG, and four additional studies found positive associations with some violence types but not others. Qualitative findings offered insights into three hypothesised pathways: disaster exposure associated with (1) an increase of stressors that trigger VAWG; (2) an increase of enabling environments for VAWG and (3) an exacerbation of underlying drivers of VAWG.ConclusionAs the first known global systematic review on the relationship between disasters from natural hazards and VAWG, this review contributes to the evidence base. We were limited by the quality of quantitative studies, specifically study designs, the measurement of variables and geographic scope. The severe health consequences of VAWG and increasing frequency of extreme events means that rigorously designed and better quality studies are needed to inform evidence-based policies and safeguard women and girls during and after disasters.
User testing of a diagnostic decision support system with machine-assisted chart review to facilitate clinical genomic diagnosis
Authors: Kulchak Rahm Alanna , Walton Nephi A , Feldman Lynn K , Jenkins Conner , Jenkins Troy , Person Thomas N , Peterson Joeseph , Reynolds Jonathon C , Robinson Peter N , Woltz Makenzie A , Williams Marc S , Segal Michael M 
Published: May 2021

ObjectivesThere is a need in clinical genomics for systems that assist in clinical diagnosis, analysis of genomic information and periodic reanalysis of results, and can use information from the electronic health record to do so. Such systems should be built using the concepts of human-centred design, fit within clinical workflows and provide solutions to priority problems.MethodsWe adapted a commercially available diagnostic decision support system (DDSS) to use extracted findings from a patient record and combine them with genomic variant information in the DDSS interface. Three representative patient cases were created in a simulated clinical environment for user testing. A semistructured interview guide was created to illuminate factors relevant to human factors in CDS design and organisational implementation.ResultsSix individuals completed the user testing process. Tester responses were positive and noted good fit with real-world clinical genetics workflow. Technical issues related to interface, interaction and design were minor and fixable. Testers suggested solving issues related to terminology and usability through training and infobuttons. Time savings was estimated at 30%–50% and additional uses such as in-house clinical variant analysis were suggested for increase fit with workflow and to further address priority problems.ConclusionThis study provides preliminary evidence for usability, workflow fit, acceptability and implementation potential of a modified DDSS that includes machine-assisted chart review. Continued development and testing using principles from human-centred design and implementation science are necessary to improve technical functionality and acceptability for multiple stakeholders and organisational implementation potential to improve the genomic diagnosis process.
Reference values and validation of the 1-minute sit-to-stand test in healthy 5–16-year-old youth: a cross-sectional study
Authors: Haile Sarah R , Fühner Thea , Granacher Urs , Stocker Julien , Radtke Thomas , Kriemler Susi 
Published: May 2021

ObjectivesIt is essential to have simple, reliable and valid tests to measure children’s functional capacity in schools or medical practice. The 1-minute sit-to-stand (STS) test is a quick fitness test requiring little equipment or space that is increasingly used in both healthy populations and those with chronic disease. We aimed to provide age-specific and sex-specific reference values of STS test in healthy children and adolescents and to evaluate its short-term reliability and construct validity.Design setting and participantsCross-sectional convenience sample from six public schools and one science fair in central Europe. Overall, 587 healthy participants aged 5–16 years were recruited and divided into age groups of 3 years each.Outcomes1-minute STS. To evaluate short-term reliability, some children performed the STS test twice. To evaluate construct validity, some children also performed a standing long jump (SLJ) and a maximal incremental exercise test.ResultsData from 547 youth aged 5–16 years were finally included in the analyses. The median number of repetitions in 1 min in males (females) ranged from 55 [95% CI: 38 to 72] (53 [95% CI: 35 to 76]) in 14–16-year olds to 59 [95% CI: 41 to 77] (60 [95% CI: 38 to 77]) in 8–10-year olds. Children who repeated STS showed a learning effect of on average 4.8 repetitions more than the first test (95% limits of agreement: −6.7 to 16.4). Moderate correlations were observed between the STS and the SLJ (r=0.48) tests and the maximal exercise test (r=0.43).ConclusionsThe reported STS reference values can be used to interpret STS test performance in children and adolescents. The STS appears to have good test–retest reliability, but a learning effect of about 10%. The association of STS with other measures of physical fitness should be further explored in a larger study and technical standards for its conduct are needed.
Exploring the actionability of healthcare performance indicators for quality of care: a qualitative analysis of the literature, expert opinion and user experience
Authors: Barbazza Erica , Klazinga Niek S , Kringos Dionne S 
Published: May 2021

BackgroundThis study explores the meaning of actionable healthcare performance indicators for quality of care-related decisions. To do so, we analyse the constructs offitness for purposeandfitness for useacross healthcare systems and in practice based on the literature, expert opinion and user experience.MethodsA multiphase qualitative study was undertaken. Phases included a literature review, a first round of one-on-one interviews with a panel of academics and thought leaders in the field (n=16), and a second round of interviews with real-world users of performance indicators (n=16). Thematic analysis was conducted between phases in order to triangulate findings in a stepwise process.ResultsCommon uses of healthcare performance indicators were differentiated within micro-meso-macro contexts of healthcare systems. Each purpose of use signals different decision-making tasks, and in effect information needs. An indicator’s fitness for use can be appraised by three clusters of considerations: methodological, contextual and managerial. Methodological considerations gauge an indicator’s perceived importance, engagement potential, interpretability, standardisation, feasibility of remedial actions, alignment to care models and sensitivity to change. Information infrastructure, system governance, workforce capacity and learning culture were found as enabling contextual considerations. Managerial considerations influencing an indicator’s use in practice were found to span the selection of indicators, data collection, analysis, display of results and delivery of information to decision-makers.ConclusionThe actionability of a healthcare performance indicator should be appraised by its alignment with the intended purpose of use beyond aggregate healthcare system levels, in combination with the extent to which methodological, contextual and managerial fitness for use considerations are met. Striking a better balance between the importance weighted to an indicator’s statistical merits and emphasis put to its fitness for purpose and use is needed for indicators that are ultimately actionable for quality of care-related decision-making.
Implantable cardioverter defibrillator devices: when, how and who should discuss deactivation with patients: a systematic literature review
Authors: Freemantle Megan , Murtagh Fliss 
Published: May 2021

BackgroundImplantable cardioverter defibrillators (ICDs) are used to treat life-threatening cardiac arrhythmias and prevent sudden cardiac arrest. As recipients age they may develop greater risk of dying as a result of progressive multimorbidity rather than sudden cardiac death. Defibrillation shocks may prolong an uncomfortable dying process. Deactivation of the defibrillator would prevent this, yet is not always discussed and planned.AimTo systematically review published evidence on ICD deactivation discussions and make recommendations on when, how and who should facilitate effective and patient-centred deactivation discussions.MethodsUsing standard systematic review methods, MEDLINE, EMBASE, CINAHL and PsycInfo were searched for studies published in the English language between 2010 and March 2021. Inclusion criteria were studies of adults (≥18 years) and including discussions on ICD deactivation and/or related communication. Included studies were independently reviewed, data extracted, quality assessed and data synthesised using a deductive approach.ResultsOf the 8893 articles identified, 22 papers met the inclusion criteria. Deductive approach led to identification of five main themes: (1) timing of ICD deactivation discussions, (2) initiation of deactivation discussions, (3) advance directives, (4) barriers to discussions and (5) facilitators of discussions.ConclusionsDespite available guidelines, conversations on device deactivation are not being undertaken consistently. Evidence suggests lack of professional awareness of guidelines and limited training in communication skills. To prevent distress and promote comfortable dying, there needs to be a proactive clinical and policy initiative in the education of both professionals and patients and their relatives about device deactivation.
Lipoprotein(a) is robustly associated with aortic valve calcium
Authors: Kaiser Yannick , Singh Sunny S , Zheng Kang H , Verbeek Rutger , Kavousi Maryam , Pinto Sara-Joan , Vernooij Meike W , Sijbrands Eric J G , Boekholdt S Matthijs , de Rijke Yolanda B , Stroes Erik S G , Bos Daniel 
Published: May 2021

ObjectivesTo investigate the prevalence and quantity of aortic valve calcium (AVC) in two large cohorts, stratified according to age and lipoprotein(a) (Lp(a)), and to assess the association between Lp(a) and AVC.MethodsWe included 2412 participants from the population-based Rotterdam Study (52% women, mean age=69.6±6.3 years) and 859 apparently healthy individuals from the Amsterdam University Medical Centers (UMC) outpatient clinic (57% women, mean age=45.9±11.6 years). All individuals underwent blood sampling to determine Lp(a) concentration and non-enhanced cardiac CT to assess AVC. Logistic and linear regression analyses were performed to investigate the associations of Lp(a) with the presence and amount of AVC.ResultsThe prevalence of AVC was 33.1% in the Rotterdam Study and 5.4% in the Amsterdam UMC cohort. Higher Lp(a) concentrations were independently associated with presence of AVC in both cohorts (OR per 50 mg/dL increase in Lp(a): 1.54 (95% CI 1.36 to 1.75) in the Rotterdam Study cohort and 2.02 (95% CI 1.19 to 3.44) in the Amsterdam UMC cohort). In the Rotterdam Study cohort, higher Lp(a) concentrations were also associated with increase in aortic valve Agatston score (β 0.19, 95% CI 0.06 to 0.32 per 50 mg/dL increase).ConclusionsLp(a) is robustly associated with presence of AVC in a wide age range of individuals. These results provide further rationale to assess the effect of Lp(a) lowering interventions in individuals with early AVC to prevent end-stage aortic valve stenosis.
Combination anti-PD1 and ipilimumab therapy in patients with advanced melanoma and pre-existing autoimmune disorders
Authors: Brown Lauren J , Weppler Alison , Bhave Prachi , Allayous Clara , Patrinely Jr J. Randall , Ott Patrick , Sandhu Shahneen , Haydon Andrew , Lebbe Celeste , Johnson Douglas B , Long Georgina V , Menzies Alexander A , Carlino Matteo S 
Published: May 2021

BackgroundClinical trials of immunotherapy have excluded patients with pre-existing autoimmune disease. While the safety and efficacy of single agent ipilimumab and anti-PD1 antibodies in patients with autoimmune disease has been examined in retrospective studies, no data are available for combination therapy which has significantly higher toxicity risk. We sought to establish the safety and efficacy of combination immunotherapy for patients with advanced melanoma and pre-existing autoimmune diseases.MethodsWe performed a retrospective study of patients with advanced melanoma and pre-existing autoimmune disease who received combination ipilimumab and anti-PD1 at 10 international centers from March 2015 to February 2020. Data regarding the autoimmune disease, treatment, toxicity and outcomes were examined in patients.ResultsOf the 55 patients who received ipilimumab and anti-PD1, the median age was 63 years (range 23–83). Forty-six were treated with ipilimumab and nivolumab and nine with ipilimumab and pembrolizumab.Eighteen patients (33%) had a flare of their autoimmune disease including 4 of 7 with rheumatoid arthritis, 3 of 6 with psoriasis, 5 of 10 with inflammatory bowel disease, 3 of 19 with thyroiditis, 1 of 1 with Sjogren’s syndrome, 1 of 1 with polymyalgia and 1 of 1 with Behcet’s syndrome and psoriasis. Eight (44%) patients ceased combination therapy due to flare. Thirty-seven patients (67%) had an unrelated immune-related adverse event (irAE), and 20 (36%) ceased combination immunotherapy due to irAEs. There were no treatment-related deaths. Patients on immunosuppression (OR 4.59; p=0.03) had a higher risk of flare.The overall response rate was 55%, with 77% of responses ongoing. Median progression free survival and overall survival were 10 and 24 months, respectively. Patients on baseline immunosuppression had an overall survival of 11 months (95% CI 3.42 to 18.58) compared with 31 months without (95% CI 20.89 to 41.11, p=0.005).ConclusionsIn patients with pre-existing autoimmune disease, not on immunosuppression and advanced melanoma, combination ipilimumab and anti-PD1 has similar efficacy compared with previously reported trials. There is a risk of flare of pre-existing autoimmune disorders, particularly in patients with inflammatory bowel disease and rheumatologic conditions, and patients on baseline immunosuppression.
IL-15 mediated expansion of rare durable memory T cells following adoptive cellular therapy
Authors: Kohli Karan , Yao Lu , Nowicki Theodore Scott , Zhang Shihong , Black Ralph Graeme , Schroeder Brett A , Farrar Erik A , Cao Jianhong , Sloan Heather , Stief Dawn , Cranmer Lee D , Wagner Michael J , Hawkins Douglas S , Pillarisetty Venu G , Ribas Antoni , Campbell Jean , Pierce Robert H , Kim Edward Y , Jones Robin L , Riddell Stanley R , Yee Cassian , Pollack Seth M 
Published: May 2021

BackgroundSynovial sarcoma (SS) and myxoid/round cell liposarcoma (MRCL) are ideal solid tumors for the development of adoptive cellular therapy (ACT) targeting NY-ESO-1, as a high frequency of tumors homogeneously express this cancer-testes antigen. Data from early phase clinical trials have shown antitumor activity after the adoptive transfer of NY-ESO-1–specific T cells. In these studies, persistence of NY-ESO-1 specific T cells is highly correlated with response to ACT, but patients often continue to have detectable transferred cells in their peripheral blood following progression.MethodWe performed a phase I clinical trial evaluating the safety of NY-ESO-1–specific endogenous T cells (ETC) following cyclophosphamide conditioning. Peripheral blood mononuclear cells (PBMCs) from treated patients were evaluated by flow cytometry and gene expression analysis as well as through ex vivo culture assays with and without IL-15.ResultsFour patients were treated in a cohort using ETC targeting NY-ESO-1 following cyclophosphamide conditioning. Treatment was well tolerated without significant toxicity, but all patients ultimately had disease progression. In two of four patients, we obtained post-treatment tumor tissue and in both, NY-ESO-1 antigen was retained despite clear detectable persisting NY-ESO-1–specific T cells in the peripheral blood. Despite a memory phenotype, these persisting cells lacked markers of proliferation or activation. However, in ex vivo culture assays, they could be induced to proliferate and kill tumor using IL-15. These results were also seen in PBMCs from two patients who received gene-engineered T-cell receptor–based products at other centers.ConclusionsETC targeting NY-ESO-1 with single-agent cyclophosphamide alone conditioning was well tolerated in patients with SS and those with MRCL. IL-15 can induce proliferation and activity in persisting NY-ESO-1–specific T cells even in patients with disease progression following ACT. These results support future work evaluating whether IL-15 could be incorporated into ACT trials post-infusion or at the time of progression.
Immune adverse events (irAEs) with adjuvant ipilimumab in melanoma, use of immunosuppressants and association with outcome: ECOG-ACRIN E1609 study analysis
Authors: Tarhini Ahmad A , Kang Ni , Lee Sandra J , Hodi F Stephen , Cohen Gary I , Hamid Omid , Hutchins Laura F , Sosman Jeffrey A , Kluger Harriet M , Eroglu Zeynep , Koon Henry B , Lawrence Donald P , Kendra Kari L , Minor David R , Lee Carrie B , Albertini Mark R , Flaherty Lawrence E , Petrella Teresa M , Streicher Howard , Sondak Vernon K , Kirkwood John M 
Published: May 2021

BackgroundThe impact of immune-related adverse events (irAEs) occurring from adjuvant use of immunotherapy and of their management on relapse-free survival (RFS) and overall survival (OS) outcomes is currently not well understood.Patients and methodsE1609 enrolled 1673 patients with resected high-risk melanoma and evaluated adjuvant ipilimumab 3 mg/kg (ipi3) and 10 mg/kg (ipi10) versus interferon-α. We investigated the association of irAEs and of use of immunosuppressants with RFS and OS for patients treated with ipilimumab (n=1034).ResultsOccurrence of grades 1–2 irAEs was associated with RFS (5 years: 52% (95% CI 47% to 56%) vs 41% (95% CI 31% to 50%) with no AE; p=0.006) and a trend toward improved OS (5 years: 75% (95% CI 71% to 79%) compared with 67% (95% CI 56% to 75%) with no AE; p=0.064). Among specific irAEs, grades 1–2 rash was most significantly associated with RFS (p=0.002) and OS (p=0.003). In multivariate models adjusting for prognostic factors, the most significant associations were seen for grades 1–2 rash with RFS (p<0.001, HR=0.70) and OS (p=0.01, HR=0.71) and for grades 1–2 endocrine+rash with RFS (p<0.001, HR=0.66) and OS (p=0.008, HR=0.7). Overall, grades 1–2 irAEs had the best prognosis in terms of RFS and OS and those with grades 3–4 had less RFS benefits and no OS advantage over no irAE. Patients experiencing grades 3–4 irAE had significantly higher exposure to corticosteroids and immunosuppressants than those with grades 1–2 (92% vs 60%; p<0.001), but no significant associations were found between corticosteroid and immunosuppressant use and RFS or OS. In investigating the impact of non-corticosteroid immunosuppressants, although there were trends toward better RFS and OS favoring cases who were not exposed, no significant associations were found.ConclusionsRash and endocrine irAEs were independent prognostic factors of RFS and OS in patients treated with adjuvant ipilimumab. Patients experiencing lower grade irAEs derived the most benefit, but we found no significant evidence supporting a negative impact of high dose corticosteroids and immunosuppressants more commonly used to manage grades 3–4 irAEs.