Ultra-Long Pharmacokinetic Properties of Insulin Degludec are Comparable in Elderly Subjects and Younger Adults with Type 1 Diabetes Mellitus

BACKGROUND: Management of diabetes in elderly subjects is complex and careful management of glucose levels is of particular importance in this population because of an increased risk of diabetes-related complications and hypoglycaemia. OBJECTIVE: The aim of this study was to evaluate the pharmacokinetic and pharmacodynamic properties of insulin degludec (IDeg), a basal insulin with an ultra-long duration of action, in elderly subjects with type 1 diabetes compared with younger adults. METHODS: This trial was a randomised, double-blind, two-period, crossover trial conducted in a single centre and included both inpatient and outpatient periods. Subjects were men and women aged 18–35 years inclusive (younger adult group) or ≥65 years (elderly group) with type 1 diabetes who received IDeg (0.4 U/kg) via subcutaneous injection in the thigh once-daily for six days. Following 6-day dosing, a 26-hour euglycaemic glucose clamp procedure was conducted to evaluate the steady-state pharmacodynamic effects of IDeg. Blood samples were taken for pharmacokinetic analysis up to 120 h post-dose. Pharmacokinetic endpoints included the total exposure of IDeg, ie the area under the IDeg serum concentration curve during one dosing interval at steady state (AUC(IDeg,τ,SS)) (τ = 0–24 h, equal to one dosing interval) and the maximum IDeg serum concentration at steady state (C(max,IDeg,SS)). Pharmacodynamic endpoints included the total glucose-lowering effect of IDeg, ie the area under the glucose infusion rate (GIR) curve at steady state (AUC(GIR,τ,SS)), and the maximum GIR at steady state (GIR(max,IDeg,SS)). RESULTS: Total exposure (AUC(IDeg,τ,SS)) and maximum concentration (C(max,IDeg,SS)) of IDeg were comparable between elderly subjects and younger adults. Estimated mean age group ratios (elderly/younger adult) for AUC(IDeg,τ,SS) and C(max,IDeg,SS) and corresponding two-sided 95 % confidence intervals (CIs) were 1.04 (95 % CI 0.73–1.47) and 1.02 (95 % CI 0.74–1.39), respectively. Mean AUC(IDeg,0–12h,SS)/AUC(IDeg,τ,SS) was 53 % in both younger adult and elderly subjects, showing that in both age groups IDeg exposure was evenly distributed across the first and second 12 h of the 24-hour dosing interval. No statistically significant differences were observed between younger adult and elderly subjects with regard to AUC(GIR,τ,SS) (the primary endpoint of this study) and GIR(max,IDeg,SS). Estimated mean age group ratios (elderly/younger adult) for AUC(GIR,τ,SS) and GIR(max,IDeg,SS) and corresponding two-sided 95 % CIs were 0.78 (95 % CI 0.47–1.31) and 0.80 (95 % CI 0.54–1.17), respectively. Duration of action was beyond the clamp duration of 26 h in all subjects. CONCLUSIONS: The exposure of IDeg at steady state during once-daily dosing was similar in younger adult and elderly subjects. The glucose-lowering effect of IDeg was numerically lower in elderly subjects compared with younger adults, but no significant differences were observed between age groups. The ultra-long pharmacokinetic and pharmacodynamic properties of IDeg observed in younger adults were preserved in elderly subjects with type 1 diabetes. Clinical trials.gov number: NCT0096441

Visual acuity, amblyopia, and vision-related quality of life in preterm adults with and without ROP : results from the Gutenberg prematurity eye study

Objectives This study investigated the effects of prematurity and ROP on visual acuity and VRQoL in adults (18–52 years). Methods The Gutenberg Prematurity Eye Study is a retrospective cohort study with a prospective ophthalmologic examination. Preterm and full-term participants at an age from 18 to 52 years were included. Distant corrected visual acuity (DCVA) and VRQoL were assessed in participants (892 eyes of 450 individuals aged 28.6 ± 8.6 years, 251 females) grouped into full-term controls (gestational age [GA] at birth ≥37 weeks), preterm participants without ROP and GA 33–36 weeks (group 2), GA 29–32 weeks (group 3), GA ≤ 28 weeks (group 4), non-treated ROP (group 5) and treated ROP (group 6). Main outcome measures were distant corrected visual acuity (DCVA), VRQoL and prevalence of amblyopia. Results The DCVA of the better eye correlated (p < 0.001) with GA, birth weight, ROP, ROP treatment, and perinatal adverse events and was poorer in both ROP groups. Visual acuity of <20/200 in the better eye was observed in two participants (4.2%) in the ROP group and one person (6.7%) in the treated ROP group. The prevalence of amblyopia increased in the ROP groups. Compared to full-term controls, visual functioning VRQoL scores were lower in preterm individuals independent of ROP while socioemotional VRQoL scores were only lower in the treated ROP group. Conclusion Participants with postnatal ROP and its treatment showed decreased visual acuity and VRQol in adulthood, with amblyopia occurring more frequently in more preterm participants with ROP

Hypertensive Retinopathy is Not Associated with Low or High Birth Weight &ndash; Results from the Population-Based German Gutenberg Health Study

Achim Fieß,1,&ast; Sandra Gißler,1,&ast; Philipp S Wild,2– 4 Karl J Lackner,5 Thomas Münzel,6 Matthias Michal,7 Michael S Urschitz,8 Norbert Pfeiffer,1 Alexander K Schuster1 1Department of Ophthalmology, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany; 2Preventive Cardiology and Preventive Medicine - Center for Cardiology, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany; 3Center for Thrombosis and Hemostasis (CTH), University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany; 4German Center for Cardiovascular Research (DZHK), Partner Site Rhine-Main, Mainz, Germany; 5Institute of Clinical Chemistry and Laboratory Medicine, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany; 6Center for Cardiology – Cardiology I, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany; 7Department of Psychosomatic Medicine and Psychotherapy, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany; 8Division of Pediatric Epidemiology, Institute for Medical Biostatistics, Epidemiology and Informatics, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany&ast;These authors contributed equally to this workCorrespondence: Achim Fieß, Department of Ophthalmology, University Medical Center of the Johannes Gutenberg University Mainz, Langenbeckstr. 1, Mainz, 55131, Germany, Tel +49-6131-17-5150, Fax +49-6131-17-8495, Email [email protected]: This study investigates the association between self-reported birth weight (BW) and the prevalence of hypertensive retinopathy (HR) in a large population-based cohort in Germany, as part of the Gutenberg Health Study (GHS). The study involved analyzing fundus photographs of 6855 participants, aged 35 to 74, to assess signs of HR, classified according to the Mitchell-Wong Classification. The research aimed to explore the correlation between fetal growth restriction indicated by BW and the frequency of HR. The results showed that the frequency of HR did not significantly differ among groups with different BW ranges. In the univariable analysis, HR was initially associated with high BW, but this association disappeared after adjusting for age, sex, and cardiovascular risk factors. No association was found between low BW and HR. The study reveals novel insights as there are no prior population-based studies specifically exploring this association.Keywords: birth weight, hypertensive retinopathy, epidemiology, population-based stud

Wie gut sehen unsere ABC-Schützen?

HINTERGURND Im Rahmen der kinderärztlichen Vorsorgeuntersuchungen U1 bis U9 von der Geburt bis zum Beginn des sechsten Lebensjahres wird unter anderem das Sehvermögen getestet – eine augenärztliche Vorsorgeuntersuchung im Kindesalter gibt es in Deutschland nicht. Diese Studie untersucht, ob eine Teilnahme an der U8 (am Ende des vierten Lebensjahres) und der U9 (zu Beginn des sechsten Lebensjahres) mit Sehschärfeergebnissen assoziiert ist, die im Rahmen der Schuleingangsuntersuchungen (SEU) erhoben werden. METHODEN Ausgewertet wurden Daten der SEU des Landes Rheinland-Pfalz der Einschulungsjahrgänge 2009/2010 bis 2014/2015. In diesen Jahrgängen wurde die Sehschärfe mittels Rodenstock-Sehtestgerät (E-Haken; Rodenstock Instrumente GmbH, Ottobrunn, Deutschland) und eigener Korrektur geprüft. Festgehalten wurden reduzierte Sehschärfen von <0,7. Der Zusammenhang zwischen der Teilnahme an den Vorsorgeuntersuchungen U8 bzw. U9 und dem Vorliegen einer ein- und beidseitigen Sehschärfe <0,7 bei SEU wurde mithilfe von multipler logistischer Regressionsanalyse untersucht und für wichtige Störgrößen adjustiert. ERGEBNISSE Daten von 189.704 Kindern (91.041 Mädchen und 98.663 Jungen) aus 35 von 36 Landkreisen konnten eingeschlossen werden. Eine Sehschärfe <0,7 wurde bei 8416 Kindern (4,4 %) ermittelt, in beiden Augen bei 4345 (2,3 %) Kindern. Die Teilnahmequote an der U8 bzw. U9 betrug 93,9 % bzw. 93,3 %. Es bestand eine negative Assoziation zwischen der Teilnahme an der U8 bzw. U9 und einem ein- oder beidseitigen SEU-Visus <0,7 (adjustierte OR: 0,68; 95 %-KI: 0,61–0,75; p < 0,01; N = 124.467/adjustierte OR: 0,57; 95 %-KI: 0,51–0,65; p < 0,01; N = 121.496). SCHLUSSFOLGERUNGEN Es zeigt sich ein hoher Anteil an Kindern mit verminderter Sehschärfe bei der Schuleingangsuntersuchung. Kinder, die in der U8 und U9 untersucht worden waren, hatten eine bessere Chance für eine gute Sehschärfe bei der Schuleingangsuntersuchung

Improving manual oxygen titration in preterm infants by training and guideline implementation

To study oxygen saturation (SpO2) targeting before and after training and guideline implementation of manual oxygen titration, two cohorts of preterm infants 21%. ABCs where oxygen therapy was given were identified and analyzed. After training and guideline implementation the %SpO2-wtr increased (median interquartile range (IQR)) 48.0 (19.6-63.9) % vs 61.9 (48.5-72.3) %; p 95% (44.0 (27.8-66.2) % vs 30.8 (22.6-44.5) %; p 95% did not decrease (73% vs 64%; ns) but lasted shorter (2 (0-7) vs 1 (1-3) minute; p < 0.004). CONCLUSION: Training and guideline implementation in manual oxygen titration improved SpO2 targeting in preterm infants with more time spent within the target range and less frequent hyperoxaemia. The durations of hypoxaemia and hyperoxaemia during ABCs were shorter. What is Known: • Oxygen saturation targeting in preterm infants can be challenging and the compliance is low when oxygen is titrated manually. • Hyperoxaemia often occurs after oxygen therapy for oxygen desaturation during apnoeas. What is New: • Training and implementing guidelines improved oxygen saturation targeting and reduced hyperoxaemia. • Training and implementing guidelines improved manual oxygen titration during ABC