bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prehospital time and mortality in patients requiring a highest priority emergency medical response: a Danish registry-based cohort study
Authors: Mills Elisabeth Helen Anna , Aasbjerg Kristian , Hansen Steen Moeller , Ringgren Kristian Bundgaard , Dahl Michael , Rasmussen Bodil Steen , Torp-Pedersen Christian , Søgaard Peter , Kragholm Kristian 
Published: November 2019

ObjectiveTo examine the association between time from emergency medical service vehicle dispatch to hospital arrival and 1-day and 30-day mortality.DesignRegister-based cohort study.SettingNorth Denmark Region (≈8000 km2, catchment population ≈600 000).ParticipantsWe included all highest priority dispatched ambulance transports in North Denmark Region in 2006–2012.InterventionsUsing logistic regression and the g-formula approach, we examined the association between time from emergency dispatch to hospital arrival and mortality for presumed heart, respiratory, cerebrovascular and other presumed medical conditions, as well as traffic or other accidents, as classified by emergency dispatch personnel.Main outcome measures1-day and 30-day mortality.ResultsAmong 93 167 individuals with highest priority ambulances dispatched, 1948 (2.1%) were dead before the ambulance arrived and 19 968 (21.4%) were transported to the hospital under highest priority (median total prehospital time from dispatch to hospital arrival 47 min (25%–75%: 35–60 min); 95th percentile 84 min). Among 18 709 with population data, 1-day mortality was 10.9% (n=2038), and was highest for patients with dyspnoea (20.4%) and lowest for patients with traffic accidents (2.8%). Thirty-day mortality was 18.3% and varied between 36.6% (patients with dyspnoea) and 3.7% (traffic accidents). One-day mortality was not associated with total prehospital time, except for presumed heart conditions, where longer prehospital time was associated with decreased mortality: adjusted OR for >60 min vs 0–30 min was 0.61 (95% CI 0.40 to 0.91). For patients with dyspnoea, OR for >60 min vs 0–30 min was 0.90 (95% CI 0.56 to 1.45), for presumed cerebrovascular conditions OR 1.41 (95% CI 0.53 to 3.78), for other presumed medical conditions OR 0.84 (95% CI 0.70 to 1.02), for traffic accidents OR 0.65 (95% CI 0.29 to 1.48) and for other accidents OR 0.84 (95% CI 0.47 to 1.51). Similar findings were found for 30-day mortality.ConclusionsIn this study, where time from emergency dispatch to hospital arrival mainly was <80 min, there was no overall relation between this prehospital time measure and mortality.
Experiences among firefighters and police officers of responding to out-of-hospital cardiac arrest in a dual dispatch programme in Sweden: an interview study
Authors: Hasselqvist-Ax Ingela , Nordberg Per , Svensson Leif , Hollenberg Jacob , Joelsson-Alm Eva 
Published: November 2019

ObjectivesThe objective of this study was to explore firefighters’ and police officers’ experiences of responding to out-of-hospital cardiac arrest (OHCA) in a dual dispatch programme.DesignA qualitative interview study with semi-structured, open-ended questions where critical incident technique (CIT) was used to collect recalled cardiac arrest situations from the participants’ narratives. The interviews where transcribed verbatim and analysed with inductive content analysis.SettingThe County of Stockholm, Sweden.ParticipantsPolice officers (n=10) and firefighters (n=12) participating in a dual dispatch programme with emergency medical services in case of suspected OHCA of cardiac or non-cardiac origin.ResultsAnalysis of 60 critical incidents was performed resulting in three consecutive time sequences (preparedness, managing the scene and the aftermath) with related categories, where first responders described the complexity of the cardiac arrest situation. Detailed information about the case and the location was crucial for the preparedness, and information deficits created stress, frustration and incorrect perceptions about the victim. The technical challenges of performing cardiopulmonary resuscitation and managing the airway was prominent and the need of regular team training and education in first aid was highlighted.ConclusionsParticipating in dual dispatch in case of suspected OHCA was described as a complex technical and emotional process by first responders. Providing case discussions and opportunities to give, and receive feedback about the case is a main task for the leadership in the organisations to diminish stress among personnel and to improve future OHCA missions.
Knowledge and attitudes of syphilis and syphilis pre-exposure prophylaxis (PrEP) among men who have sex with men in Vancouver, Canada: a qualitative study
Authors: Nath Ronita , Grennan Troy , Parry Robin , Baharuddin Fahmy , Connell James P , Wong Jason , Grace Daniel 
Published: November 2019

ObjectivesIn British Columbia, Canada, syphilis is at record-high rates, with over 80% of cases in 2017 seen in gay, bisexual and other men who have sex with men (GBM). The syphilis epidemic is of particular concern for those living with HIV, since syphilis may lead to more serious complications in this population. We sought to explore syphilis-related knowledge and attitudes around biomedical prevention options for syphilis, with the goal of informing effective strategies to prevent syphilis.DesignWe conducted a qualitative study consisting of in-depth, individual interviews from December 2016 to June 2017. Our interviews focused on participants’ knowledge about syphilis and perceptions regarding syphilis pre-exposure prophylaxis (PrEP). Interviews were analysed using Grounded Theory.ParticipantsTwenty-five GBM were interviewed (64% white; median age: 43 years), including men living with HIV and/or with a history of syphilis.SettingVancouver, British Columbia.ResultsFive interrelated themes emerged. First, GBM were aware of the local syphilis epidemic. Second, syphilis-related knowledge differed according to syphilis and HIV serostatus. Third, competing ideas emerged regarding men’s concerns about syphilis. While our participants expressed concern about getting syphilis, they also described the importance of sexual pleasure. Fourth, many participants said that syphilis was not perceived to be alarming; preventing HIV infection remained a primary concern for many. Finally, while syphilis PrEP was appealing to those living with HIV or a prior syphilis diagnosis, others were concerned about antibiotic resistance, cost and side effects.ConclusionsOur participants organised their safer sex strategies around HIV, not syphilis. Although syphilis-related knowledge was relatively high among GBM living with HIV and those with a prior syphilis diagnosis, this knowledge did not appear to be related with safer sexual practices, such as increased condom use. This work highlights the importance of examining other potential prevention solutions, such as syphilis PrEP.
Assessment on patient outcomes of primary hip replacement: an interrupted time series analysis from ‘The National Joint Registry of England and Wales’
Authors: Garriga Cesar , Murphy Jacqueline , Leal Jose , Arden Nigel K , Price Andrew James , Prieto-Alhambra Daniel , Carr Andrew J , Rangan Amar , Cooper Cyrus , Peat George , Fitzpatrick Ray , Barker Karen L , Judge Andrew 
Published: November 2019

ObjectivesEffects of the UK Department of Health’s national Enhanced Recovery After Surgery (ERAS) Programme on outcomes after primary hip replacement.DesignNatural experimental study using interrupted time series to assess the changes in trends before, during and after ERAS implementation (April 2009 to March 2011).SettingSurgeries in the UK National Joint Registry were linked with Hospital Episode Statistics containing inpatient episodes from National Health Service trusts in England and patient reported outcome measures.ParticipantsPatients aged ≥18 years from 2008 to 2016.Main outcome measuresRegression coefficients of monthly means of length of hospital stay, bed day cost, change in Oxford Hip Scores (OHS) 6 months post-surgery, complications 6 months post-surgery and revision rates 5 years post-surgery.Results438 921 primary hip replacements were identified. Hospital stays shortened from 5.6 days in April 2008 to 3.6 in December 2016. There were also improvements in bed day costs (£7573 in April 2008 to £5239 in December 2016), positive change in self-reported OHS from baseline to 6 months post-surgery (17.7 points in April 2008 to 22.9 points in December 2016), complication rates (4.1% in April 2008 to 1.7% March 2016) and 5 year revision rates (5.9 per 1000 implant-years (95% CI 4.8 to 7.2) in April 2008 to 2.9 (95% CI 2.2 to 3.9) in December 2011). The positive trends in all outcomes started before ERAS was implemented and continued during and after the programme.ConclusionsPatient outcomes after hip replacement have improved over the last decade. A national ERAS programme maintained this improvement but did not alter the existing rate of change.
Examination of CIs in health and medical journals from 1976 to 2019: an observational study
Authors: Barnett Adrian Gerard , Wren Jonathan D 
Published: November 2019

ObjectivesPrevious research has shown clear biases in the distribution of published p values, with an excess below the 0.05 threshold due to a combination of p-hacking and publication bias. We aimed to examine the bias for statistical significance using published confidence intervals.DesignObservational study.SettingPapers published inMedlinesince 1976.ParticipantsOver 968 000 confidence intervals extracted from abstracts and over 350 000 intervals extracted from the full-text.Outcome measuresCumulative distributions of lower and upper confidence interval limits for ratio estimates.ResultsWe found an excess of statistically significant results with a glut of lower intervals just above one and upper intervals just below 1. These excesses have not improved in recent years. The excesses did not appear in a set of over 100 000 confidence intervals that were not subject to p-hacking or publication bias.ConclusionsThe huge excesses of published confidence intervals that are just below the statistically significant threshold are not statistically plausible. Large improvements in research practice are needed to provide more results that better reflect the truth.
Association of the low e′ and high E/e′ with long-term outcomes in patients with normal ejection fraction: a hospital population-based observational cohort study
Authors: Seko Yuta , Kato Takao , Shiba Masayuki , Morita Yusuke , Yamaji Yuhei , Haruna Yoshizumi , Nakane Eisaku , Hayashi Hideyuki , Haruna Tetsuya , Inoko Moriaki 
Published: November 2019

ObjectiveWe aimed to evaluate the association of the severity of left ventricular (LV) diastolic dysfunction with long-term outcomes in patients with normal ejection fraction.DesignRetrospective study.SettingA single centre in Japan.ParticipantsWe included 3576 patients who underwent both scheduled transthoracic echocardiography and ECG between 1 January and 31 December 2013, in a hospital-based population after excluding valvular diseases or low ejection fraction (<50%) or atrial fibrillation and categorised them into three groups: septal tissue Doppler early diastolic mitral annular velocity (e′)≥7 (without relaxation disorder, n=1593), e′<7 and early mitral inflow velocity (E)/e′≤14 (with relaxation disorder and normal LV end-diastolic pressure, n=1337) and e′<7 and E/e′>14 (with relaxation disorder and high LV end-diastolic pressure, n=646).Primary and secondary outcome measuresThe primary outcome measure was a composite of all-cause death and major adverse cardiac events (MACE). The secondary outcome measure were all-cause death and MACE, separately.ResultsThe cumulative 3-year incidences of the primary outcome measures were significantly higher in the e′<7 and E/e′≤14 (19.0%) and e′<7 and E/e′>14 group (23.4%) than those for the e′≥7 group (13.0%; p<0.001). After adjusting for confounders, the excess 3-year risk of primary outcome for the groups with e′<7 and E/e′≤14 related to e′≥7 (HR: 1.24; 95% CI 1.02 to 1.52) and e′<7 and E/e′>14 related to e′<7 (HR: 1.57; 95% CI 1.28 to 1.94) were significant. The severity of diastolic dysfunction was associated with incrementally higher risk for primary outcomes (p<0.001).ConclusionThe severity of LV diastolic dysfunction using e′<7 and E/e′>14 was associated with the long-term prognosis in patients with normal ejection fraction in an incremental fashion.
How many serial sections are needed to detect apoptosis in endoscopic biopsies with gastrointestinal graft versus host disease?
Authors: Wong Newton ACS , Marks David I 
Published: November 2019

AimsThe hallmark histological feature of acute gastrointestinal graft versus host disease (GI GVHD) is epithelial apoptosis. This is the first formal evaluation of how many serial sections are required to consistently detect apoptotic bodies in endoscopic biopsies from various GI locations in patients with clinically validated GI GVHD.Methods, results and conclusionsAssessment of 1008 serial sections showed that apoptotic bodies are uniformly distributed among such sections of gastric, duodenal and colorectal biopsies from these patients. Assessment of 59 further biopsies showed that assessing 12 serial sections should suffice to detect GVHD in gastric, duodenal and colorectal biopsies using thresholds of one apoptotic body per biopsy fragment or one apoptotic body per 4 mm2. Assessing 12 serial sections should also suffice to detect GVHD in duodenal and colorectal biopsies using the threshold of 6 apoptotic bodies per 10 contiguous crypts, but it remains uncertain whether this assessment and threshold can be applied to gastric biopsies.
The Anticancer Activity of Lycium barbarum Polysaccharide by Inhibiting Autophagy in Human Skin Squamous Cell Carcinoma Cells In Vitro and In Vivo
Authors: Zeng Meihua , Kong Qingtao , Liu Fang , Chen Jun , Sang Hong 
Published: November 2019

Objective. This study is aimed at investigating the effects of Lycium barbarum polysaccharide (LBP) on the proliferation and apoptosis of human cutaneous squamous cell carcinoma A431 cells in vitro and in vivo via its regulation on autophagy. Methods. In vitro experiment: A431 cells were treated with different concentrations of LBP, and cell viability was measured by the CCK8 method. Flow cytometry was used to detect the cell apoptosis rate. The expression of Ki67, PCNA, cl-caspase-3, Bcl-2, and LC3II and the phosphorylation status of JNK and ERK1/2, as well as the effect of SP600125 cotreatment on the expression of autophagy and apoptosis-associated proteins, were determined via Western blot. In vivo experiment: a transplanted tumor model was established by subcutaneous injection of A431 cells to the nude mice. 50 mg/kg LBP was injected into the mice intraperitoneally; the survival rate of mice, volume, and weight of tumor were determined on the 30th day. The expression of Ki67 and MMP-2 proteins was measured by immunohistochemistry. Results. LBP at concentrations of 400 μg/ml and above was significantly cytotoxic to A431 cells, whereas, within the dose range of 50 μg/ml~200 μg/ml, LBP significantly inhibited the expression of Ki67 and PCNA proteins, promoted the expression of cl-caspase-3, inhibited the expression of Bcl-2 protein, downregulated the expression of autophagy marker LC3II, and reduced the phosphorylation of ERK1/2, whereas the level of JNK phosphorylation was upregulated. At the same time, the regulation of Beclin1, LC3II, Bcl-2, and cl-caspase-3 by LBP was effectively reversed by the cotreatment of SP600125. In addition, LBP increased the survival rate of transplanted nude mice, reduced tumor volume and weight, and downregulated the expression of Ki67 and MMP-2. Conclusion. LBP can induce apoptosis of A431 cells by inhibiting autophagy and can inhibit tumor growth in vivo.
Antidrug Antibodies Against Immune Checkpoint Blockers: Impairment of Drug Efficacy or Indication of Immune Activation?
Authors: Enrico Diego , Paci Angelo , Chaput Nathalie , Karamouza Eleni , Besse Benjamin 
Published: November 2019

Abstract
The generation of antibodies following exposure to therapeutic drugs has been widely studied, however in oncology, data in relation to their clinical relevance are limited. Antidrug antibodies (ADAs) can cause a decrease in the amount of drug available, resulting in some cases in decreased antitumor activity and a consequent impact on clinical outcomes. Several immunologic factors can influence the development of ADAs, and in addition, the sensitivity of the different testing methods used in different studies can vary, representing an additional potential confounding factor. The reported frequency of ADA-positive patients following treatment with immune checkpoint inhibitors varies from as low as 1.5% for pembrolizumab to 54% for atezolizumab. This latter drug is the only immune checkpoint inhibitor to have undergone an expanded analysis of the clinical implications of ADAs, but with discordant results. Given that immune checkpoint inhibitors can modify the immune response and potentially impact ADA formation, data from published as well as prospective trials need to be evaluated for a better understanding of the clinical implications of ADAs in this setting.
Determining the Predominant Lesion in Patients With Severe Aortic Stenosis and Coronary Stenoses
Authors: Ahmad Yousif , Vendrik Jeroen , Eftekhari Ashkan , Howard James P. , Cook Christopher , Rajkumar Christopher , Malik Iqbal , Mikhail Ghada , Ruparelia Neil , Hadjiloizou Nearchos , Nijjer Sukhjinder , Al-Lamee Rasha , Petraco Ricardo , Warisawa Takayuki , Wijntjens Gilbert W.M. , Koch Karel T. , van de Hoef Tim , de Waard Guus , Echavarria-Pinto Mauro , Frame Angela , Sutaria Nilesh , Kanaganayagam, Gajen , Ariff Ben , Anderson Jon , Chukwuemeka, Andrew , Fertleman Michael , Koul Sasha , Iglesias Juan F. , Francis Darrel , Mayet Jamil , Serruys Patrick , Davies Justin , Escaned Javier , van Royen Niels , Götberg Matthias , Juhl Terkelsen Christian , Høj Christiansen Evald , Piek Jan J. , Baan Jan , Sen Sayan 
Published: November 2019

Background:
Patients with severe aortic stenosis (AS) often have coronary artery disease. Both the aortic valve and the coronary disease influence the blood flow to the myocardium and its ability to respond to stress; leading to exertional symptoms. In this study, we aim to quantify the effect of severe AS on the coronary microcirculation and determine if this is influenced by any concomitant coronary disease. We then compare this to the effect of coronary stenoses on the coronary microcirculation.

Methods:
Group 1: 55 patients with severe AS and intermediate coronary stenoses treated with transcatheter aortic valve implantation (TAVI) were included. Group 2: 85 patients with intermediate coronary stenoses and no AS treated with percutaneous coronary intervention were included. Coronary pressure and flow were measured at rest and during hyperemia in both groups, before and after TAVI (group 1) and before and after percutaneous coronary intervention (group 2).

Results:

Microvascular resistance over the wave-free period of diastole increased significantly post-TAVI (pre-TAVI, 2.71±1.4 mm Hg·cm·s
−1
versus post-TAVI 3.04±1.6 mm Hg·cm·s
−1
[
P
=0.03]). Microvascular reserve over the wave-free period of diastole significantly improved post-TAVI (pre-TAVI 1.88±1.0 versus post-TAVI 2.09±0.8 [
P
=0.003]); this was independent of the severity of the underlying coronary stenosis. The change in microvascular resistance post-TAVI was equivalent to that produced by stenting a coronary lesion with an instantaneous wave-free ratio of ≤0.74.

Conclusions:
TAVI improves microcirculatory function regardless of the severity of underlying coronary disease. TAVI for severe AS produces a coronary hemodynamic improvement equivalent to the hemodynamic benefit of stenting coronary stenoses with instantaneous wave-free ratio values <0.74. Future trials of physiology-guided revascularization in severe AS may consider using this value to guide treatment of concomitant coronary artery disease.
Know Place: Heaven’s Gate and American Gnosticism
Authors: Gutierrez Cathy 
Published: November 2019

Abstract
Bonnie Nettles and Marshall Applewhite, the founders of the millenarian movement Heaven’s Gate, began teaching at a retreat they called Know Place, where one came to “know thyself” in the “no-place of Utopia.” This initial phase set the stage for a process of self-recognition that would become the hallmark of conversion to the movement, much as Gnosticism employed in the first centuries of the common era. The parallels between late antique Gnosticism and Heaven’s Gate are remarkable. Both posited two breeds of humans, one a material husk and the other an enlightened soul temporarily trapped on earth. Both proposed radical gender equality and maintained a rigorous ascetic regime. Both proffered death as a return to a prior state of gnosis rather than a disjuncture into a new life and afterlife. This paper examines the rhetoric of self-verification employed by both movements as it relates to a modified monotheism.
Unusual Trapped Mountain Lee Waves with Deep Vertical Penetration and Significant Stratospheric Amplitude
Authors: Metz Johnathan J. , Durran Dale R. , Blossey Peter N. 
Published: November 2019

Abstract
Simulations of the weather over the South Island of New Zealand on 28 July 2014 reveal unusual wave activity in the stratosphere. A series of short-wavelength perturbations resembling trapped lee waves were located downstream of the topography, but these waves were in the stratosphere, and their crests were oriented north–south, in contrast to both the northeast–southwest orientation of the spine of the Southern Alps and the crests of trapped waves present in the lower troposphere. Vertical cross sections through these waves show a nodal structure consistent with that of a higher-order trapped-wave mode. Eigenmode solutions to the vertical structure equation for two-dimensional, linear, Boussinesq waves were obtained for a horizontally homogeneous sounding representative of the 28 July case. These solutions include higher-order modes having large amplitude in the stratosphere that are supported by just the zonal wind component. Two of these higher-order modes correspond to trapped waves that develop in an idealized numerical simulation of the 28 July 2014 case. These higher-order modes are trapped by very strong westerly winds in the midstratosphere and are triggered by north–south-oriented features in the subrange-scale topography. In contrast, the stratospheric cross-mountain wind component is too weak to trap similar high-order modes with crest-parallel orientation.