bluuebunny/crossref_metadata_2025_split huggingface dataset:
Colon cleansing efficacy and safety with 1 L NER1006 versus sodium picosulfate with magnesium citrate: a randomized phase 3 trial
Authors: Schreiber Stefan , Baumgart Daniel , Drenth Joost , Filip Rafał , Clayton Lucy , Hylands Kerry , Repici Alessandro , Hassan Cesare ,   on behalf of the DAYB Study Group
Published: August 2018

Abstract
Background Polyethylene glycol (PEG) bowel preparations are widely used for precolonoscopy bowel cleansing. This phase 3 trial assessed the efficacy, safety, and tolerability of the novel 1 L PEG-based NER1006 vs. sodium picosulfate plus magnesium citrate (SP + MC) in day-before dosing.
Methods Patients requiring colonoscopy were randomized (1 : 1) to receive NER1006 or SP + MC. Cleansing was assessed on the Harefield Cleansing Scale (HCS) and Boston Bowel Preparation Scale (BBPS) using central readers. Two primary end points were assessed: overall colon cleansing success and high-quality cleansing of the right colon. Intention-to-treat (modified full analysis set [mFAS]) and per protocol (PP) analyses were performed.
Results Of 515 patients, efficacy was analyzed in 501 (NER1006, n = 250; SP + MC, n = 251) and 379 patients (NER1006, n = 172; SP + MC, n = 207) in the mFAS and PP analyses, respectively. Non-inferiority of NER1006 vs. SP + MC was established in the mFAS for both overall cleansing (62.0 % vs. 53.8 %; P = 0.04) and high-quality cleansing in the right colon (4.4 % vs. 1.2 %; P = 0.03). Superiority of NER1006 was demonstrated using HCS in the PP set for overall cleansing success (68.0 % vs. 57.5 %; P = 0.02) and right colon high-quality cleansing (5.2 % vs. 1.0 %; P = 0.02) and using BBPS in the mFAS for overall cleansing success (58.4 % vs. 45.8 %; P = 0.003) and right colon high-quality cleansing (4.0 % vs. 0.8 %; P = 0.02). Mean segmental scores for 4/5 segments were higher with NER1006 (P ≤ 0.04). Both treatments were well tolerated, with more mild adverse events for NER1006 (17.0 % vs. 10.0 %; P = 0.03).
Conclusions Colon cleansing with NER1006 vs. SP + MC was non-inferior (mFAS) and superior (PP), with acceptable safety.European Clinical Trials Database (EudraCT)2014-002186-30TRIAL REGISTRATION: Multicenter, randomized, parallel group, phase 3 study 2014-002186-30 at https://eudract.ema.europa.eu/
Dietary Intervention with Oatmeal in Patients with uncontrolled Type 2 Diabetes Mellitus – A Crossover Study
Authors: Delgado Graciela , Kleber Marcus E. , Krämer Bernhard K , Morcos Michael , Humpert Per M. , Wiegand Kerstin , Mauldin Andy , Kusterer Klaus , Enghöfer Michael , März Winfried , Segiet Thomas , Lammert Alexander 
Published: August 2018

Abstract
Background In a pilot study, we evaluated the efficacy of two days of oatmeal on insulin resistance and glucose metabolism and found a marked decrease of insulin requirements. The most important shortcoming of that study was that the interventions were not isocaloric (diabetes adapted diet: 1500 kcal/d vs. oatmeal 1100 kcal/d). To address these drawbacks we designed the OatMeal And Insulin Resistance (OMA-IR) study.
Methods The study was a randomized, open label crossover dietary intervention study with consecutive inclusion of 15 patients with uncontrolled type 2 diabetes. The intervention comprised two days of oatmeal on days 3 and 4 of a 5 days hospital stay. During the control period, patients received a diabetes mellitus adapted diet only. The primary endpoint was the daily insulin requirement and glycemic control.
Results Upon oatmeal treatment, the required insulin dose could be significantly reduced on the third and fourth day as compared to the second day of inpatient stay (82.0±30.3 and 69.9±29.9IU versus 112±36.2IU;P<0.001). During control treatment, insulin requirement did not change. There were no significant differences in the changes of mean blood glucose or fasting glucose between both treatments. HbA1c was lower four weeks after the oatmeal intervention.
Conclusion In this crossover study, two days of oatmeal intervention allowed a highly significant reduction of required daily insulin doses while maintaining adequate metabolic control as compared to a diabetes adapted diet only. The beneficial effects of the intervention might last for several weeks as shown by the lower HbA1c four weeks after the intervention.
The Prognostic Importance of Impaired Fasting Glycemia in Chronic Coronary Heart Disease Patients
Authors: Slezák David , Mayer Otto , Bruthans Jan , Seidlerová Jitka , Rychecká Martina , Gelžinský Julius , Mateřánková Markéta , Karnosová Petra , Wohlfahrt Peter , Cífková Renata , Filipovský Jan 
Published: August 2018

Abstract
Objectives Impaired glucose metabolism represents one the most important cardiovascular risk factors, with steeply raising prevalence in overall population. We aimed to compare mortality risk of impaired fasting glycaemia (IFG) and overt diabetes mellitus (DM) in patients with coronary heart disease (CHD).
Study design prospective cohort study
Methods A total of 1685 patients, 6–24 months after myocardial infarction and/or coronary revascularization at baseline, were followed in a prospective cohort study. Overt DM was defined as fasting glucose ≥ 7 mmol/L and/or use of antidiabetic treatment, while IFG as fasting glucose 5.6–6.99 mmol/L, but no antidiabetic medication. The main outcomes were total and cardiovascular mortality during 5 years of follow-up.
Results During follow-up of 1826 days, 172 patients (10.2%) deceased, and of them 122 (7.2%) from a cardiovascular cause. Both exposures, overt DM (n=623, 37.0% of the whole sample) and IFG (n=436, 25.9%) were associated with an independent increase of 5-year total mortality, compared to normoglycemic subjects [fully adjusted hazard risk ratio (HRR) 1.63 (95%CI: 1.01–2.61)]; p=0.043 and 2.25 (95%CI: 1.45–3.50); p<0.0001, respectively]. In contrast, comparing both glucose disorders one with each other, no significant differences were found for total mortality [HRR 0.82 (0.53–1.28); p=0.33]. Taking 5-years cardiovascular mortality as outcome, similar pattern was observed [HRR 1.96 (95%CI: 1.06–3.63) and 3.84 (95%CI: 2.19–6.73) for overt DM and IFG, respectively, with HRR 0.63 (95%CI: 0.37–1.07) for comparison of both disorders].
Conclusions Impaired fasting glycaemia adversely increases mortality of CHD patients in the same extent as overt DM.
Advances in Sharing Multi-sourced Health Data on Decision Support Science 2016-2017
Authors: Shankar Prabhu , Anderson Nick 
Published: August 2018

Introduction: Clinical decision support science is expanding to include integration from broader and more varied data sources, diverse platforms and delivery modalities, and is responding to emerging regulatory guidelines and increased interest from industry.
Objective: Evaluate key advances and challenges of accessing, sharing, and managing data from multiple sources for development and implementation of Clinical Decision Support (CDS) systems in 2016-2017.
Methods: Assessment of literature and scientific conference proceedings, current and pending policy development, and review of commercial applications nationally and internationally.
Results: CDS research is approaching multiple landmark points driven by commercialization interests, emerging regulatory policy, and increased public awareness. However, the availability of patient-related “Big Data” sources from genomics and mobile health, expanded privacy considerations, applications of service-based computational techniques and tools, the emergence of “app” ecosystems, and evolving patient-centric approaches reflect the distributed, complex, and uneven maturity of the CDS landscape. Nonetheless, the field of CDS is yet to mature. The lack of standards and CDS-specific policies from regulatory bodies that address the privacy and safety concerns of data and knowledge sharing to support CDS development may continue to slow down the broad CDS adoption within and across institutions.
Conclusion: Partnerships with Electronic Health Record and commercial CDS vendors, policy makers, standards development agencies, clinicians, and patients are needed to see CDS deployed in the evolving learning health system.
Findings from 2017 on Consumer Health Informatics and Education: Health Data Access and Sharing
Authors: Staccini Pascal , Lau Annie ,   Section Editors for the IMIA Yearbook Section on Consumer Health Informatics and Education
Published: August 2018

Objective: To summarize the state of the art during the year 2017 in consumer health informatics and education, with a special emphasis on sharing health data and accessing personal health information (PHI) from patients' and consumers' perspective.
Methods: We conducted a systematic search of articles published in PubMed using a predefined set of queries which identified 228 potential articles for review. The section editors then screened these articles according to topic relevance and selected 15 candidate best papers for full review and scoring by a panel of international experts. Based on the scores and the reviews, four papers received the highest score and were selected in a consensus meeting as the best papers on health data access and sharing from consumers' and patients' perspective.
Results: These four papers were categorised into the following topics: 1) data sharing for research and governance in privacy protection; 2) use of personal health information and individual privacy concerns; and 3) consumers' views and demographic characteristics regarding health data sharing and the use of digital health portals. Overall, it was surprising to see only a small number of papers reporting original research in this area.
Conclusions: Patients understand the need for sharing information to facilitate best care and to enrich biomedical knowledge. When confronted with the reality of accessing information systems for their own information, patients are concerned about usability as well as privacy. Overall, there is a need for more emphasis on: 1) considering privacy as a feature defined by design; 2) using specific consent approaches and data sharing mechanisms for recruiting clinical trial participants; 3) taking into account socio-demographic characteristics when promoting consumer access to personal health information; and 4) defining indicators of high-quality care to incorporate healthcare professionals' level of caution when accessing patients' medical information and fostering patient trust in data exchange. Ultimately, privacy mechanisms should be part of the design process and not only be implemented when security has been breached and violated.
NORMAL SYNTHESIS AND EXPRESSION OF ENDOTHELIAL GP IIb/IIIa IN GLANZMANN'S THROMBASTENIA
Authors: Giltay J C , Leeksma O C , Breederveld C , van Mourik J A 
Published: August 2018

In Glanzmann’s thrombastenia (GT), an autosomal recessive inherited hemorrhagic disease, the platelet membrane glycoprotein (GP) IIb/IIIa complex is absent or reduced. Recently we and others demonstrated that cultured human umbilical vein endothelial cells synthesize a membrane protein complex that is structurally closely related to GP IIb/IIIa. Endothelial cells of thrombasthénie patients could, therefore be deficient in GP IIb/IIIa. We had the opportunity to culture endothelial cells isolated from the umbilical cord of a newborn with GT and to examine the plasma membrane composition of these cells. Employing a variety of immunochemical techniques, including immunoprecipitation, immunofluorescence staining and crossed immunoelectrophoresis, we demonstrated that the endothelial cells of the patient were indistinguishable from normal endothelial cells in their ability to synthesize and express GP IIb/IIIa. Our results indicate that GT is not accompanied by and "endotheliopathy".Zwa (P1A1) is an alloantigen, located on platelet GP IIIa, and, consequently, Zwa is absent on GT platelet. Data will he presented which show that not only normal endothelial IIIa carries the Zwa antigen, hut also GT endothelial cells normally express Zwa. This finding supports our view that GT endothelial GP IIb/IIIa is indistinguishable from normal endothelial GP IIb/IIIa. Moreover, this finding directly shows that the thrombastenic glycoprotein abnormality and the inheritance of Zwa antigen are controlled by different genes.
A FREQUENT TAQI RFLP AND A GENE LESION OR RARE TAQI RFLP IN THE VON WILLEBRAND FACTOR GENE
Authors: Marchetti G , Guerra S , Ballerini G , Patracchini P , Volinia S , Bernardi F 
Published: August 2018

A cDNA for vonWi11ebrand factor (vWf) has been used to investigate lesions and RFLPs in the vWf gene.In hybridizations with the 3'cDNA portion (a 2 Kb SacI fragment) a frequent polymorphism has been found with TaqI restriction enzyme. The alleles are 3.3 Kb and 2.6 Kb ; the frequencies of 0.51 and 0.49 respectively enable to investigate an appreciable portion of vW disease (vWd) families.In a patient with type III vWd an abnormal TaqI pattern has been observed. A 4.5 Kb band is absent and an additional band of 2.3 Kb is present.This pattern has been inherited from the consanguineous heterozygous parents and has been traced in several members of this large family. The presence of the abnormal gene pattern is related to total or partial vWf deficiency in the family and has not been found in several normal subjects. The BamHI and BglII restriction patterns are normal and suggest a small mutation originating a new TaqI site.These findings are compatible with a gene lesion or a rare RFLP.Work supported by Ricerca Sanitaria Finalizzata Regione Emilia Romagna.
REGULATION OF PLASMINOGEN ACTIVATOR INHIBITOR-1 mRNA IN HUMAN ENDOTHELIAL CELLS
Authors: van den Berg E A , Sprengers E , Jaye M , Burgess W , van Hinsbergh V W M 
Published: August 2018

Cultured human endothelial cells (HEC) increase their production of plasminogen activator inhibitor (PAI-1) upon stimulation with endotoxin and IL-1, agents that are known to cause an increase in PAI-1 levels in vivo. In order to study the regulation of PAI-1 synthesis at the mRNA level, we isolated a cDNA clone for the human PAI-1 gene from an endothelial expression cDNA library in λ gt 11 by screening with a PAI-1 specific antibody. Three positive cross-hybridizing clones were isolated. The longest insert (1500 bp) was partially sequenced (1000 bp). The sequence was identical to the PAI-1 sequence recently reported by others. The identity of the cDNA clone was further confirmed by comparison with part of the amino acid sequence of PAI-1. For that purpose t-PA-PAI-1 complex was purified from HEC conditioned medium by immunoadsorption to anti-t-PA IgG, and a suitable peptide was sequenced after comparison of the HPLC elution profiles of CNBr digests of t-PA and t-PA-PAI-1 complex. The amino acid sequence (M)FRQFQADFT completely matches the sequence predicted from the cDNA sequence.By hybridization of the cDNA probe to Northern blots of total cellular RNA from human umbilical vein and artery EC (HUVEC, HUAEC), two transcripts of 2.3 and 3 kb were found. Primary HUAEC, incubated for 18 hours in growth medium, produced considerable although variable levels of PAI-1 activity and contained PAI-1 mRNA levels comparable to those found in subcultured HUAEC. When subcultured HUEC were incubated for 6 h with endotoxin, IL-1 or TNF, a 2-fold increase in PAI-1 mRNA was found with each of these mediators. Stimulation of the cells in the presence of cycloheximide resulted in a further increase of the 3 kb PAI-1 transcript. The 3’ end of this transcript contains a 75 bp AT-rich sequence. Similar 3’ AT-rich sequences have been found in mRNA’s for a number of inflammatory mediators and cellular oncogenes, and in some cases it has been shown that removal of the sequence increased mRNA stability. The influence of cyclohex-imid on the larger PAI-1 transcript might be explained by inhibition of synthesis of a specific nuclease that controls the level of mRNA’s harbouring such an AT rich sequence.
ON THE IDENTITY OF PLATELET FIBRINOGEN WITH PLASMA FIBRINOGEN
Authors: Kaudewitz H , Henschen A , Zimmermann R E 
Published: August 2018

It is a well established fact that fibrinogen occurs not only in blood plasma but also in the α-granules of the platelets. Recently, it has been shown that fibrinogen is synthesised in the megakaryocytes as well as in the liver. Plasma fibrinogen is derived from the liver, but platelet fibrinogen either exclusively or partially from the megakaryocytes. Conclusive, proteinche-mical evidence for the identity of the fibrinogens from the two biosynthetic sources has previously not been produced. However, the two fibrinogen preparations have been shown to have the same overall peptide chain composition, to be thrombin-clottable and release fibrinopeptides of A- and B-type, and to react with antibodies against plasma fibrinogen. The two preparations differ in the way that platelet fibrinogen lacks the higher-molecular-mass γ-chain variant.The aim of the present investigation was to conduct a detailed proteinchemical comparison between human plasma and platelet fibrinogen. For this purpose, fibrin(ogen)s from the two sources were mercaptolysed, alkylated and the three peptide chains isolated by reversed-phase high-performance liquid chromatography (HPLC). The peptide chains were then analysed directly for amino-terminal sequence and for carboxyterminal sequence by isolation of a terminal fragment. The HPLC-fingerprint patterns of the cyanogen bromide-cleaved chains were compared. The native fibrinogens were also treated with thrombin and the fibrinopeptide type distribution determined by reversed-phase HPLC. The carbohydrate side chain compositions were established by ion-exchange-chromatographic methods after acid hydrolysis. So far no previously unrecognized differences have been observed.
PEAKING TIME OF CK-MB IN PATIENTS TREATED WITH THROMBOLYTIC AGENTS DURING MYOCARDIAL INFARCTION: IS IT REALLY A CLUE TO REPERFUSION?
Authors: Brunelli C , Spallarossa P , Ghigliotti G , lannetti M , Caponneto S 
Published: August 2018

Aim of the study is to evaluate the relevance of CK-MB peaking time as a marker of reperfusion in patients (pts) treated with thrombolytic agent. 150 pts were recruited in 4 centers and randomized into two treatment groups: Group A = conventional therapy + urokinase (2.000.000 U i.v.),Group B = conventional therapy. Inter val between onset of symptoms and beginning of therapy was 3.50 ± 1.25 hrs in group A and 3.45±1.20 hrs in group B. Serum cardiac en zyme determination was performed every 4 hrs for 48 hrs. On day 20 all pts underwent coronary angiography and ventriculography. Cl ini. cal and angiographic data were not significantly different in the two groups. Patency of infart related artery (IRA) was evident in 51% of pts of group A vs 38% of pts in group B (p<0.05). In 119 pts both IRA status and complete CK-MB curve were known. Mean time to peak CK-MB in pts with patent and occluded IRA was 18.7±1.6 hrs and 24.4±1.4 hrs respectively (p<0.02); 15 hrs from onset of symptoms was considered as the boundary between early and late peak.11 pts died in hospital: 3 in group A and 8 in group B.Conclusion: 1) CK-MB peak time is significantly different in pts with patent and occluded vessels. 2) From a clinical point of view in conventionally treated pts IRA status is not predicted by CK-4'B peaking time, while in urokinase treated pts IRA status is predicted only by early peaking.
FIBRINOGEN DOSAGE AS A SYSTEMIC MARKER OF UNSUCCESSFUL INTRAVENOUS STREPTOKINASE IN ACUTE MYOCARDIAL INFARCTION
Authors: Col-De Beys Ch , Lavenne-Pardonge E , Moriau M , Renkin J , Col J 
Published: August 2018

Whether failure to timely recanalize coronary artery with intravenous streptokinase (SK) is related to inadequate fibrinolysis remains controversial. Since coagulation might also interfere with the course of clot lysis, this relation was investigated in 27 patients (pts) pretreated with heparin (10.000 IU bolus). 500.000 to 1.500.000 IU SK were infused in 45 min, 160 ± 60 min after the onset of infarct.Angiographic control, performed 219 ± 199 min after SK, showed persistent coronary occlusion in 5 pts (0CC) and patency in 22 (PAT), unrelated to SK dosage. One to 3 hours post SK, fibrinogen (Fg) (Clauss Method) was undetectable in all 22 PAT and 4/5 0CC. However, Fg (and clottable breakdown products) assessed by Gram's method* was detected in all 5 OCC and 3/22 PAT (164 ± 89 VS 13 ± 38 mg %, p < 0.005). Prolongation of thrombin time (neutralized with protamine) was limited in OCC, compared to PAT (59 ± 6 VS 96 ± 11 sec, p < 0.005), supporting the hypothesis of the presence of clottable material in OCC. These results were accompanied by slight differences of ELT (< 20 min in 2/5 OCC VS 21/22 PAT) and non significant differences in plasminogen (1.78 ± 1 VS 2.18 ± 1.1 mg/dl ; NS), α2 antiplasmin (1.7 ± 1.7 VS 3.9 ± 6.9 % ; NS), plasmin (12 ± 4 VS 16 ± 11 mm2 ; NS) and plasminogen activators (95 ± 41 VS 105 ± 23 mm2 ; NS).Conclusion : at similar systemic lytic activity induced by SK, failure of arterial recanalization was associated wih an apparent incomplete fibrinogenolysis (and fibrinolysis) in 20 % of the patients.*Gram H.C. - A new method of determination of the fibrin percent in blood and plasma - J Biol Chem 49 : 279 - 295 (1921)mean ± SD
COAGULATION STUDIES IN PATIENTS WITH ACUTE MYOCARDIAL INFARCTION DURING THROMBOLYTIC TREATMENT WITH APSAC (BRL-26921) OR STREPTOKINASE
Authors: Hoffmann J , Bonnier J , de Swart J 
Published: August 2018

We studied 70 patients with acute myocardial infarction in a multicenter trial comparing intravenous anisoylated plasminogen-streptokinase activator complex (APSAC or BRL-26921; 30 U in 2-4 min) with intracoronary streptokinase (SK; 250,000 U in 1 hour). Blood for coagulation and fibrinolytic determinations was taken before and 1 1/2,12,24 and 48 h after thrombolytic treatment. There were 65 patients in whom fibrinogen decreased by more than 10% of pretreatment; this was defined as a systemic lytic state. Of these patients,33 were treated with APSAC and 32 with SK. The lowest fibrinogen was found at 1 1/2 h : about 15% and 22% of baseline, respectively. Also plasminogen and α2-antiplasmin reached low levels at 1 1/2h hour. Plasminogen mean 32 ± 11 % and 34 ± 9% of pretreatment for APSAC and SK , respectively and a2-antiplasmin to less than 5% and 6 + 9 %. Fibrin(ogen) degradation products peaked at lh h,too. The mean FDP was significantly higher in the APSAC group than in the SK group (739 vs. 355 mg/L). The global coagulation assays APTT, PT, TT and reptilase time all yielded comparable results: peak values at l^h and no difference between both groups. After 24 to 48 hours all parameters had returned to their baseline levels, except FDP which was still elevated.The euglobilin clot lysis time(ECLT) showed a different picture: after a very rapid decrease in both groups, ECLT quickly rose to normal in the SK group, but it remained shortened in the APSAC group at 24 and even 48 h. This sustained fibrinolytic activity was significantly different from SK.In the 5 patients without systemic lytic state (3 APSAC; 2 SK), only minor changes in the parameters measured were found, except a decrease in ECLT at 1 1/2h in three of them and a slight drop in α2-antiplasmin in 2 patients. Two of these patients had a very high SK-resistance titer before treatment.It is concluded that both APSAC and SK cause a profound systemic lytic state in the majority of patients, but the degree of this systemic lysis did not significantly differ between both groups. The total fibrinolytic activity, measured as ECLT, sustained for a significantly longer period in the APSAC group than in the SK group, which probably explains the low reocclusion rate of APSAC.