Efficacy and safety of oral semaglutide with flexible dose adjustment versus sitagliptin in type 2 diabetes (PIONEER 7): a multicentre, open-label, randomised, phase 3a trial

Background: Oral semaglutide is the first oral formulation of a glucagon-like peptide-1 (GLP-1) receptor agonist developed for the treatment of type 2 diabetes. We aimed to compare the efficacy and safety of flexible dose adjustments of oral semaglutide with sitagliptin 100 mg. Methods: In this 52-week, multicentre, randomised, open-label, phase 3a trial, we recruited patients with type 2 diabetes from 81 sites in ten countries. Patients were eligible if they were aged 18 years or older (19 years or older in South Korea), had type 2 diabetes (diagnosed ≥90 days before screening), HbA1c of 7·5–9·5% (58–80 mmol/mol), and were inadequately controlled on stable daily doses of one or two oral glucose-lowering drugs (for 90 days or more before screening). Participants were randomly assigned (1:1) by use of an interactive web-response system, stratified by background glucose-lowering medication at screening, to oral semaglutide with flexible dose adjustments to 3, 7, or 14 mg once daily or sitagliptin 100 mg once daily. To approximate treatment individualisation in clinical practice, oral semaglutide dose could be adjusted on the basis of prespecified HbA1c and tolerability criteria. Two efficacy-related estimands were prespecified: treatment policy (regardless of treatment discontinuation or use of rescue medication) and trial product (on treatment and without use of rescue medication) for participants randomly assigned to treatment. The primary endpoint was achievement of HbA1c of less than 7% (53 mmol/mol) at week 52 and the confirmatory secondary efficacy endpoint was change in bodyweight from baseline to week 52. Safety was assessed in all participants who received at least one dose of study drug. This trial is registered with ClinicalTrials.gov, number NCT02849080, and European Clinical Trials Database, EudraCT number 2015-005593-38, and an open-label extension is ongoing. Findings: Between Sept 20, 2016, and Feb 7, 2017, of 804 patients assessed for eligibility, 504 were eligible and randomly assigned to oral semaglutide (n=253) or sitagliptin (n=251). Most participants were male (285 [57%] of 504) with a mean age of 57·4 years (SD 9·9). All participants were given at least one dose of their allocated study drug except for one participant in the sitagliptin group. From a mean baseline HbA1c of 8·3% (SD 0·6%; 67 mmol/mol [SD 6·4]), a greater proportion of participants achieved an HbA1c of less than 7% with oral semaglutide than did with sitagliptin (treatment policy estimand: 58% [134 of 230] vs 25% [60 of 238]; and trial product estimand: 63% [123 of 196] vs 28% [52 of 184]). The odds of achieving an HbA1c of less than 7% was significantly better with oral semaglutide than sitagliptin (treatment policy estimand: odds ratio [OR] 4·40, 95% CI 2·89–6·70, p<0·0001; and trial product estimand: 5·54, 3·54–8·68, p<0·0001). The odds of decreasing mean bodyweight from baseline to week 52 were higher with oral semaglutide than with sitagliptin (estimated mean change in bodyweight, treatment policy estimand: −2·6 kg [SE 0·3] vs −0·7 kg [SE 0·2], estimated treatment difference [ETD] −1·9 kg, 95% CI −2·6 to −1·2; p<0·0001; and trial product estimand: −2·9 kg [SE 0·3] vs −0·8 kg [SE 0·3], ETD −2·2 kg, −2·9 to −1·5; p<0·0001). Adverse events occurred in 197 (78%) of 253 participants in the oral semaglutide group versus 172 (69%) of 250 in the sitagliptin group, and nausea was the most common adverse event with oral semaglutide (53 [21%]). Two deaths occurred in the sitagliptin group during the trial. Interpretation: Oral semaglutide, with flexible dose adjustment, based on efficacy and tolerability, provided superior glycaemic control and weight loss compared with sitagliptin, and with a safety profile consistent with subcutaneous GLP-1 receptor agonists. Funding: Novo Nordisk A/S

Jugend-Check zum Entwurf eines Sechsundzwanzigsten Gesetzes zur Änderung des Bundesausbildungsförderungsgesetzes (26. BAföGÄndG) (Stand: 09.01.2019)

Mit dem 26. BAföG-Änderungsgesetz werden die BAföG-Sätze an aktuelle Entwicklungen angepasst und das Ziel verfolgt, förderungsberechtigte Personen wieder besser zu erreichen. Der Gesetzentwurf sieht eine Erhöhung der Bedarfssätze in zwei Stufen, jeweils zum Wintersemester bzw. zum Schuljahresbeginn, vor. 2019 werden diese Sätze um fünf Prozent und 2020 um zwei Prozent angehoben, vgl. § 12 Abs. 1 und 2, § 13 Abs. 1 BAföG. So wird der monatliche Grundbedarf für Studierende beispielsweise von 399 Euro pro Monat auf 419 Euro bzw. 427 Euro in den Jahren 2019 und 2020 festgesetzt. Zudem wird die Wohnkostenpauschale für Studierende sowie für Schülerinnen und Schüler, die Fachschulklassen , Abendgymnasien oder Kollegs besuchen und nicht bei ihren Eltern wohnen, von derzeit 250 Euro auf 325 Euro pro Monat erhöht, vgl. § 13 Abs. 2 BAföG. Des Weiteren werden die Einkommensfreibeträge in drei Schritten erhöht: 2019 um 7 Prozent, 2020 um 3 Prozent und 2021 um 6 Prozent. Damit steigt z.B. der Grundfreibetrag von Elterneinkommen von derzeit 1.715 Euro im Monat in drei Schritten auf 2.000 Euro im Jahr 2021, § 25 Abs. 1 Nr. 1 BAföG. Zudem werden 2020 die Freibeträge für eigenes Vermögen des Auszubildenden von 7.500 Euro auf 8.200 Euro angehoben, § 29 Abs. 1 Nr. 1 BAföG. Im Zuge der Erhöhung der Bedarfssätze werden ebenso die Kranken- und Pflegeversicherungszuschläge angehoben, wobei erstmals die Zusatzbelastungen durch erhobene Zusatzbeiträge der Krankenkassen Berücksichtigung finden, vgl. § 13a BAföG. Die monatliche Mindestrate zur Rückzahlung der Ausbildungsförderung (BAföG) wird in Anlehnung an die vorgenommenen Neuregelungen auf 130 Euro im Monat angehoben, § 18 Abs. 3 BAföG. In diesem Zusammenhang wird die maximale Rückzahlungsdauer des Darlehens auf 20 Jahre begrenzt, § 18 Abs. 3 BAföG. Dies gilt fortan auch für diejenigen, die für eine gewisse Dauer von den Zahlungen befreit wurden. Zudem wird die Rückzahlung auf 77 Monatsraten begrenzt, § 18 Abs. 13 BAföG. Zum Wintersemester 2019/2020 wird ein zinsfreies Staatsdarlehen (Volldarlehen) eingeführt, welches das verzinsliche Bankdarlehen der Kreditanstalt für Wiederaufbau (KfW) ersetzt. Dieses verzinsliche Darlehen wird derzeit häufig als „Hilfe zum Studienabschluss“ in Anspruch genommen, nachdem die BAföG-Förderungsdauer durch Überschreiten der Regelstudienzeit endet. Letztlich soll die zweijährige Berichtspflicht der Bundesregierung von 2019 auf 2021 verschoben werden, § 35 S. 4 BAföG. Der Bericht bildet die Grundlage zur Anpassung der Bedarfssätze und Freibeträge. Weiterhin wird der Katalog der Ausbildungsstätten, die in den Förderungsbereich des BAföG einbezogen sind, um private Berufsakademien ohne Hochschuleigenschaft, sog. Akademien im tertiären Bereich, ergänzt, vgl. § 2 Abs. 1 S.1 Nr. 5 und 6 BAföG

Preparation and thermal stress analysis of AI<inf>2o3</inf> insulation coatings on ss-304 tape

Al2O3 insulation coatings are grown on long-length stainless steel (SS) tapes using reel-to-reel sol-gel method for applications of HTS/LTS coils and magnets. Various ceramic solutions are prepared from Al based precursors, solvent and chelating agent, the coating are fabricated on SS substrates. Al2O3 solution was successfully obtained using Al-sec-butoxide precursor, and isopropanol and acetylacetone as solvent and chelating agents, respectively. In order to improve adhesion of Al2O3 on the SS-304 tapes, triethanolamine was used in the solution. The residual stresses are investigated at different temperature ranges, between (630, 600, 580, and 550 degrees C) and room temperature for different thicknesses (12, 10 and 7 mu m). The maximum stress values are obtained as 0.756 GPa as tension on substrate (SS) for the 12 mu m coating and 1.0 GPa as compression for the 7 mu m Al2O3 coating at 630 degrees C. The surface morphology and microstructure of samples are characterized by a scanning electron microscope (SEM). SEM observation revealed that Al2O3 coatings have crack and mosaic structure

Structural and mechanical properties of ZnMgO nanoparticles

This study reports the effect of annealing temperature on the structure and mechanical properties of Zn0.95Mg0.05O bulk samples by using digital Vickers microhardness tester, X-ray diffraction analysis, scanning electron microscopy and electron dispersive X-ray measurements. The samples were prepared using Zn and Mg based alkoxed by the sol-gel technique and annealed at various temperatures (500, 600, 700 and 800 degrees C). Vickers microhardness, elastic modulus, yield strength and fracture toughness values of Zn0.95Mg0.05O bulk samples were separately calculated and compared with each other. The experimental results of hardness measurements were analyzed using Meyer's law, Proportional Specimen Resistance (PSR) and Elastic/Plastic Deformation (EPD) models and Hays-Kendall (HK) approach. Finally, it was seen that HK approach is the most successful model for the microhardness analysis of these materials. (C) 2013 Elsevier B.V. All rights reserved

A comparison of the measurements with biochemical markers of bone turnover and bone mineral density in the assessment of the efficiency of osteoporosis treatment [Osteporoz tedavisinin etkinliginin degerlendirilmesinde kemik döngüsü biyokimyasal belirteçleri ve kemik mineral yogunlugu ölçümlerinin karşilaştirilmasi]

Objectives: This study aims to compare the measurements using biochemical markers of bone turnover and bone mineral density (BMD) in the assessment of the efficiency of osteoporosis treatment. Patients and methods: Between March 2006 and December 2008, 166 patients with osteoporosis in our clinic were included. Patients who were out of contact due to death or other reasons during follow-up were excluded. We compared the measurements of urinary biochemical markers of bone turnover using cross-linked N-telopeptide (Ntx) values and BMD in 60 patients (49 females, 11 males; mean age: 65.7 years; range: 42 to 87 years) with osteoporosis who were treatment-naive and completed study. Results: Twenty-nine (48.3%) of the patients received surgical treatment, while 31 (51.7%) received conservative therapy. Urine NTx values of the patients decreased 38.82% at three months; 51.99% at six months and 66.41% at 12 months. Lumbar vertebra BMD increased by 20.7% and femur neck BMD increased by 11.9% at the end of the first year. Conclusion: Urine NTx values respond to osteoporosis treatment faster than BMD measurements; thereby it may be suitable to use this parameter for the monitorization of the treatment efficiency

Association of serum total antioxidant capacity and total oxidant status with pain perception in patients with myofacial pain dysfunction

We aimed to find out the association of total antioxidant capacity (TAC) and total oxidant status (TOS) with generalized pressure pain thresholds (PPT) of patients with myofacial pain dysfunction (MPD). PPT scores of patients with MPD (n 37) and healthy individuals (n 43) were measured on the hypothenar region of the hand using a mechanical algometer. Serum samples were collected and TAC and TOS were measured by novel methods. The TAC of patients was significantly lower than that of the control subjects. The difference between the TOS measurements of patients and control subjects was not significant. The PPT scores of the patients were significantly lower than that of control subjects. There may be an association between serum antioxidant capacity and MPD. Low serum TAC might also be related with pain perception. © 2009 Informa UK Ltd All rights reserved

Causes of fetal and neonatal death

Autopsy was performed on 601 out of 654 (91.9%) fetus and newborn cases of death which occurred during a four-year period between 1988-1991 at Istanbul University Cerrahpasa Faculty of Medicine, Gynecology Department and Neonatal Unit. According to autopsy findings, among the main causes of death in newborns were infection, hyaline membrane disease, congenital anomalies, perinatal hypoxia and immaturity, and in the fetal period, perinatal hypoxia, asphyxia and congenital anomalies. In these cases, when pathologic and clinical findings were examined, it was observed that in 204 out of 301 newborn cases (67.8%) the clinical findings were well correlated with the autopsy findings; in 97 (32.2%) of the remaining cases the main disease and primary causes of death could not be determined through clinical findings; in 69 (23%) cases, in addition to the clinical diagnosis on autopsy, miner defects were determined on autopsy which were not directly related to death. When clinical and autopsy findings were compared, diagnoses with the highest discordance were pulmonary hemorrhage infection and intracranial hemorrhage

Magnetic resonance imaging and morphometric histologic analysis of prostate tissue composition in predicting the clinical outcome of terazosin therapy in benign prostatic hyperplasia

Purpose: To determine whether magnetic resonance imaging (MRI) or quantitative color-imaged morphometric analysis (MA) of the prostate gland are related to the clinical response to terazosin. Methods: Thirty-six male patients with symptomatic benign prostatic hyperplasia (BPH) with a serum prostate-specific antigen level of 4-10 ng/mL underwent MRI with body coil, transrectal prostate ultrasonography and biopsy prior to terazosin therapy. For MRI-determined stromal and non-stromal BPH, the ratio of the signal intensity of the inner gland to the obturator internus muscle was evaluated. Histologic sections were stained with hematoxylin and eosin. The MA of the specimens was performed by Samba 2000. Results of the two techniques were interpreted according to the terazosin therapy results. Results: The mean stromal percentage was 60.5 ± 18.0%. No statistically significant relationship was found between the clinical outcome of terazosin and the MRI findings. The MA results showed a significant relationship between the percentage of stroma and the percent change of the peak urinary flow rate, but not with the percent change of the international prostate symptom score after terazosin therapy (P < 0.05). Conclusion: Magnetic resonance imaging alone is not sufficient in predicting the response to terazosin therapy. Morphometric analysis of BPH tissue composition can be used in predicting the clinical outcome of terazosin therapy but it is suitable only in patients for whom prostatic biopsy is necessary in order to rule out prostate cancer