TY - JOUR A1 - Zinman, Bernard A1 - Inzucchi, Silvio E. A1 - Lachin, John M. A1 - Wanner, Christoph A1 - Ferrari, Roberto A1 - Fitchett, David A1 - Bluhmki, Erich A1 - Hantel, Stefan A1 - Kempthorne-Rawson, Joan A1 - Newman, Jennifer A1 - Johansen, Odd Erik A1 - Woerle, Hans-Juergen A1 - Broedl, Uli C. T1 - Rationale, design, and baseline characteristics of a randomized, placebo-controlled cardiovascular outcome trial of empagliflozin (EMPA-REG OUTCOME (TM)) JF - Cardiovascular Diabetology N2 - Background: Evidence concerning the importance of glucose lowering in the prevention of cardiovascular (CV) outcomes remains controversial. Given the multi-faceted pathogenesis of atherosclerosis in diabetes, it is likely that any intervention to mitigate this risk must address CV risk factors beyond glycemia alone. The SGLT-2 inhibitor empagliflozin improves glucose control, body weight and blood pressure when used as monotherapy or add-on to other antihyperglycemic agents in patients with type 2 diabetes. The aim of the ongoing EMPA-REG OUTCOME (TM) trial is to determine the long-term CV safety of empagliflozin, as well as investigating potential benefits on macro-/microvascular outcomes. Methods: Patients who were drug naive (HbA(1c) >= 7.0% and <= 9.0%), or on background glucose-lowering therapy (HbA(1c) >= 7.0% and <= 10.0%), and were at high risk of CV events, were randomized (1:1:1) and treated with empagliflozin 10 mg, empagliflozin 25 mg, or placebo (double blind, double dummy) superimposed upon the standard of care. The primary outcome is time to first occurrence of CV death, non-fatal myocardial infarction, or non-fatal stroke. CV events will be prospectively adjudicated by an independent Clinical Events Committee. The trial will continue until >= 691 confirmed primary outcome events have occurred, providing a power of 90% to yield an upper limit of the adjusted 95% CI for a hazard ratio of <1.3 with a one-sided a of 0.025, assuming equal risks between placebo and empagliflozin (both doses pooled). Hierarchical testing for superiority will follow for the primary outcome and key secondary outcomes (time to first occurrence of CV death, non-fatal myocardial infarction, non-fatal stroke or hospitalization for unstable angina pectoris) where non-inferiority is achieved. Results: Between Sept 2010 and April 2013, 592 clinical sites randomized and treated 7034 patients (41% from Europe, 20% from North America, and 19% from Asia). At baseline, the mean age was 63 +/- 9 years, BMI 30.6 +/- 5.3 kg/m(2), HbA1c 8.1 +/- 0.8%, and eGFR 74 +/- 21 ml/min/1.73 m(2). The study is expected to report in 2015. Discussion: EMPA REG OUTCOME (TM) will determine the CV safety of empagliflozin in a cohort of patients with type 2 diabetes and high CV risk, with the potential to show cardioprotection. KW - glycemic control KW - blood pressure KW - macrovascular KW - doule blind KW - chronic kidney disease KW - type-1 diabetes mellitus KW - safety KW - metformin KW - add-on KW - albuminuria KW - sulfonylurea KW - efficacy KW - canagliflozin KW - microvascular KW - SGLT2 inhibitor KW - type 2 diabetes KW - body weight KW - empagliflozin Y1 - 2014 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-116036 SN - 1475-2840 VL - 13 IS - 102 ER - TY - JOUR A1 - Stein, Kiera A1 - Maruf, Abdullah Al A1 - Müller, Daniel J. A1 - Bishop, Jeffrey R. A1 - Bousman, Chad A. T1 - Serotonin transporter genetic variation and antidepressant response and tolerability: a systematic review and meta-analysis JF - Journal of Personalized Medicine N2 - Antidepressants are used to treat several psychiatric disorders; however, a large proportion of patients do not respond to their first antidepressant therapy and often experience adverse drug reactions (ADR). A common insertion–deletion polymorphism in the promoter region (5-HTTLPR) of the serotonin transporter (SLC6A4) gene has been frequently investigated for its association with antidepressant outcomes. Here, we performed a systematic review and meta-analysis to assess 5-HTTLPR associations with antidepressants: (1) response in psychiatric disorders other than major depressive disorder (MDD) and (2) tolerability across all psychiatric disorders. Literature searches were performed up to January 2021, yielding 82 studies that met inclusion criteria, and 16 of these studies were included in the meta-analyses. Carriers of the 5-HTTLPR LL or LS genotypes were more likely to respond to antidepressant therapy, compared to the SS carriers in the total and European ancestry-only study populations. Long (L) allele carriers taking selective serotonin reuptake inhibitors (SSRIs) reported fewer ADRs relative to short/short (SS) carriers. European L carriers taking SSRIs had lower ADR rates than S carriers. These results suggest the 5-HTTLPR polymorphism may serve as a marker for antidepressant outcomes in psychiatric disorders and may be particularly relevant to SSRI treatment among individuals of European descent. KW - 5-HTTLPR KW - genotype KW - pharmacogenetics KW - antidepressant KW - efficacy KW - tolerability KW - SLC6A4 Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-252294 SN - 2075-4426 VL - 11 IS - 12 ER - TY - JOUR A1 - Sauerbrei, A. A1 - Langenhan, T. A1 - Brandstädt, A. A1 - Schmidt-Ott, R. A1 - Krumbholz, A. A1 - Girschick, H. A1 - Huppertz, H. A1 - Kaiser, P. A1 - Liese, J. A1 - Streng, A. A1 - Niehues, T. A1 - Peters, J. A1 - Sauerbrey, A. A1 - Schroten, H. A1 - Tenenbaum, T. A1 - Wirth, S. A1 - Wutzler, P. T1 - Prevalence of antibodies against influenza A and B viruses in children in Germany, 2008 to 2010 JF - Eurosurveillance N2 - The prevalence of influenza A and B virus-specific IgG was determined in sera taken between 2008 and 2010 from 1,665 children aged 0-17 years and 400 blood donors in Germany. ELISA on the basis of whole virus antigens was applied. Nearly all children aged nine years and older had antibodies against influenza A. In contrast, 40% of children aged 0-4 years did not have any influenza A virus-specific IgG antibodies. Eighty-six percent of 0-6 year-olds, 47% of 7-12 year-olds and 20% of 13-17 year-olds were serologically naive to influenza B viruses. By the age of 18 years, influenza B seroprevalence reached approximately 90%. There were obvious regional differences in the seroprevalence of influenza B in Germany. In conclusion, seroprevalences of influenza A and influenza B increase gradually during childhood. The majority of children older than eight years have basal immunity to influenza A, while comparable immunity against influenza B is only acquired at the age of 18 years. Children aged 0-6 years, showing an overall seroprevalence of 67% for influenza A and of 14% for influenza B, are especially at risk for primary infections during influenza B seasons. KW - disease KW - healthy children KW - vaccine KW - burden KW - hospitalizations KW - efficacy Y1 - 2014 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-117347 SN - 1560-7917 VL - 19 IS - 5 ER - TY - JOUR A1 - Rose, Markus A. A1 - Damm, Oliver A1 - Greiner, Wolfgang A1 - Knuf, Markus A1 - Wutzler, Peter A1 - Liese, Johannes G. A1 - Krüger, Hagen A1 - Wahn, Ulrich A1 - Schaberg, Tom A1 - Schwehm, Markus A1 - Kochmann, Thomas F. A1 - Eichner, Martin T1 - The epidemiological impact of childhood influenza vaccination using live-attenuated influenza vaccine (LAIV) in Germany: predictions of a simulation study JF - BMC Infectious Diseases N2 - Background: Routine annual influenza vaccination is primarily recommended for all persons aged 60 and above and for people with underlying chronic conditions in Germany. Other countries have already adopted additional childhood influenza immunisation programmes. The objective of this study is to determine the potential epidemiological impact of implementing paediatric influenza vaccination using intranasally administered live-attenuated influenza vaccine (LAIV) in Germany. Methods: A deterministic age-structured model is used to simulate the population-level impact of different vaccination strategies on the transmission dynamics of seasonal influenza in Germany. In our base-case analysis, we estimate the effects of adding a LAIV-based immunisation programme targeting children 2 to 17 years of age to the existing influenza vaccination policy. The data used in the model is based on published evidence complemented by expert opinion. Results: In our model, additional vaccination of children 2 to 17 years of age with LAIV leads to the prevention of 23.9 million influenza infections and nearly 16 million symptomatic influenza cases within 10 years. This reduction in burden of disease is not restricted to children. About one third of all adult cases can indirectly be prevented by LAIV immunisation of children. Conclusions: Our results demonstrate that vaccinating children 2-17 years of age is likely associated with a significant reduction in the burden of paediatric influenza. Furthermore, annual routine childhood vaccination against seasonal influenza is expected to decrease the incidence of influenza among adults and older people due to indirect effects of herd protection. In summary, our model provides data supporting the introduction of a paediatric influenza immunisation programme in Germany. KW - vaccination KW - live-attenuated influenza vaccine KW - children KW - transmission model KW - metanalysis KW - recommendations KW - hospitalizations KW - burden KW - infection KW - young children KW - seasonal influenza KW - United States KW - disease KW - efficacy KW - Germany KW - influenza Y1 - 2014 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-117563 SN - 1471-2334 VL - 14 IS - 40 ER - TY - JOUR A1 - Kleinschnitz, Christoph A1 - Niemczyk, Gabriele A1 - Rehberg-Weber, Karin A1 - Wernsdörfer, Colin T1 - Interferon Beta-1a (AVONEX®) as a treatment option for untreated patients with multiple sclerosis (AXIOM): a prospective, observational study JF - International Journal of Molecular Sciences N2 - The efficacy and safety of first-line disease-modifying therapies (DMT) for relapsing-remitting multiple sclerosis (RRMS) has been demonstrated in pivotal, randomized trials, but these studies do not reflect the routine care setting where treatment gaps or switches are common. The Avonex as Treatment Option for Untreated MS Patients (AXIOM) trial assessed the efficacy of newly-initiated intramuscular interferon beta-1a (IM IFNb-1a) after a treatment-free interval, with particular consideration of the previous course of disease and therapy. The AXIOM trial was an open, 12-month, observational, non-interventional study with a retrospective and a prospective part conducted in Germany. RRMS patients with a treatment-free interval of at least three months were included and treated with IFNb-1a for up to 12 months. Relapse rate, disability progression, injection-related parameters and quality of life observed during the prospective part were compared with retrospectively-collected data. Two hundred and thirty five RRMS patients participated in AXIOM. The mean relapse rate decreased from 1.1 in the three months before baseline to 0.2 per quarter during the twelve-month observational period; the Multiple Sclerosis Functional Composite score improved during twelve months of IM IFNb-1a treatment, while the Expanded Disability Status Scale score did not change over the course of this study. Compared to previous DMTs (IM IFNb-1a, subcutaneous IFNb-1a (SC IFNb-1a), SC IFNb-1b, glatiramer acetate), the patients experienced less injection site reactions and flu-like symptoms, with a stated improved quality of life. IM IFNb-1a was effective and well accepted in RRMS patients with no or discontinued previous therapy. These results from the routine care setting may inform optimization of DMT treatment in RRMS, but need confirmation in further studies. KW - subcutaneous injection KW - therapy KW - trial KW - relapsing-remitting multiple sclerosis KW - injection site reactions; KW - efficacy KW - quality of life KW - disease-modifying therapy Y1 - 2015 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-148487 VL - 16 ER - TY - JOUR A1 - Hautmann, Christopher A1 - Döpfner, Manfred A1 - Katzmann, Josepha A1 - Schürmann, Stephanie A1 - Wolff Metternich-Kaizman, Tanja A1 - Jaite, Charlotte A1 - Kappel, Viola A1 - Geissler, Julia A1 - Warnke, Andreas A1 - Jacob, Christian A1 - Hennighausen, Klaus A1 - Haack-Dees, Barbara A1 - Schneider-Momm, Katja A1 - Philipsen, Alexandra A1 - Matthies, Swantje A1 - Rösler, Michael A1 - Retz, Wolfgang A1 - Gontard, Alexander von A1 - Sobanski, Esther A1 - Alm, Barbara A1 - Hohmann, Sarah A1 - Häge, Alexander A1 - Poustka, Luise A1 - Colla, Michael A1 - Gentschow, Laura A1 - Freitag, Christine M. A1 - Becker, Katja A1 - Jans, Thomas T1 - Sequential treatment of ADHD in mother and child (AIMAC study): importance of the treatment phases for intervention success in a randomized trial JF - BMC Psychiatry N2 - Background The efficacy of parent-child training (PCT) regarding child symptoms may be reduced if the mother has attention-deficit/hyperactivity disorder (ADHD). The AIMAC study (ADHD in Mothers and Children) aimed to compensate for the deteriorating effect of parental psychopathology by treating the mother (Step 1) before the beginning of PCT (Step 2). This secondary analysis was particularly concerned with the additional effect of the Step 2 PCT on child symptoms after the Step 1 treatment. Methods The analysis included 143 mothers and children (aged 6–12 years) both diagnosed with ADHD. The study design was a two-stage, two-arm parallel group trial (Step 1 treatment group [TG]: intensive treatment of the mother including psychotherapy and pharmacotherapy; Step 1 control group [CG]: supportive counseling only for mother; Step 2 TG and CG: PCT). Single- and multi-group analyses with piecewise linear latent growth curve models were applied to test for the effects of group and phase. Child symptoms (e.g., ADHD symptoms, disruptive behavior) were rated by three informants (blinded clinician, mother, teacher). Results Children in the TG showed a stronger improvement of their disruptive behavior as rated by mothers than those in the CG during Step 1 (Step 1: TG vs. CG). In the CG, according to reports of the blinded clinician and the mother, the reduction of children’s disruptive behavior was stronger during Step 2 than during Step 1 (CG: Step 1 vs. Step 2). In the TG, improvement of child outcome did not differ across treatment steps (TG: Step 1 vs. Step 2). Conclusions Intensive treatment of the mother including pharmacotherapy and psychotherapy may have small positive effects on the child’s disruptive behavior. PCT may be a valid treatment option for children with ADHD regarding disruptive behavior, even if mothers are not intensively treated beforehand. Trial registration ISRCTN registry ISRCTN73911400. Registered 29 March 2007. KW - mothers KW - children KW - adult treatment KW - parent training KW - efficacy Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-227930 VL - 18 ER - TY - JOUR A1 - Detomas, Mario A1 - Altieri, Barbara A1 - Deutschbein, Timo A1 - Fassnacht, Martin A1 - Dischinger, Ulrich T1 - Metyrapone versus osilodrostat in the short-term therapy of endogenous Cushing’s syndrome: results from a single center cohort study JF - Frontiers in Endocrinology N2 - Background Although surgery is considered the first-line treatment for patients with endogenous Cushing’s syndrome (CS), medical therapy is often required to control severe hypercortisolism. Metyrapone and osilodrostat are both steroidogenic inhibitors targeting the 11β-hydroxylase, however, their therapeutic effectiveness has not yet been directly compared. This study aimed to evaluate metyrapone and osilodrostat in the short-term therapy of CS. Methods Retrospective analysis of patients with endogenous CS treated with metyrapone or osilodrostat as monotherapy for at least 4 weeks. Main outcome measures were serum cortisol and 24h urinary free cortisol (UFC) at baseline (T0) and after 2 (T1), 4 (T2), and 12 weeks (T3) of therapy. Results 16 patients with endogenous CS were identified (pituitary n=7, adrenal n=4, ectopic CS n=5). Each 8 patients were treated with metyrapone and osilodrostat. Despite heterogeneity, both groups showed comparable mean UFC levels at T0 (metyrapone: 758 µg/24h vs osilodrostat: 817 µg/24h; p=0.93). From T0 to T1, the decrease of UFC was less pronounced under metyrapone than osilodrostat (-21.3% vs -68.4%; median daily drug dose: 1000 mg vs 4 mg). This tendency persisted at T2 (-37.3% vs -50.1%; median drug dose: 1250 mg vs 6 mg) while at T3 a decrease in UFC from T0 was more pronounced in the metyrapone group (-71.5% vs -51.5%; median dose 1250 mg vs 7 mg). Under osilodrostat, a QTc-interval prolongation was identified at T3 (mean 432 ms vs 455 ms). From T0 to T2, the number of antihypertensive drugs remained comparable under metyrapone and decreased under osilodrostat (n= -0.3 vs n= -1.0). Conclusion Although both drugs show comparable therapeutic efficacy, osilodrostat seems to reduce cortisol levels and to control blood pressure faster. KW - metyrapone KW - osilodrostat KW - Cushing’s syndrome KW - hypercortisolism KW - medical therapy KW - blood pressure KW - isturisa KW - efficacy Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-277477 SN - 1664-2392 VL - 13 ER -