Changes in acromegaly comorbidities, treatment, and outcome over three decades: a nationwide cohort study

ObjectiveTo study the time-dependent changes in disease features of Danish patients with acromegaly, including treatment modalities, biochemical outcome, and comorbidities, with a particular focus on cancer and mortality.MethodsPertinent acromegaly-related variables were collected from 739 patients diagnosed since 1990. Data are presented across three decades (1990–1999, 2000–2009, and 2010–2021) based on the year of diagnosis or treatment initiation.ResultsAdenoma size and insulin-like growth factor I (IGF-I) levels at diagnosis did not differ significantly between study periods. The risk of being diagnosed with diabetes, heart disease, sleep apnea, joint disease, and osteoporosis increased from the 1990s to the later decades, while the mortality risk declined to nearly half. The risk of cancer did not significantly change. Treatment changed toward the use of more medical therapy, and fewer patients underwent repeat surgeries or pituitary irradiation. A statistically significant increase in the proportion of patients achieving IGF-I normalization within 3–5 years was observed over time (69%, 83%, and 88%). The proportion of patients with three or more deficient pituitary hormones decreased significantly over time.ConclusionModern medical treatment regimens of acromegaly as well as increased awareness and improved diagnostics for its comorbidities have led to better disease control, fewer patients with severe hypopituitarism, and declining mortality in the Danish cohort of acromegaly patients. The risk of cancer did not increase over the study period

Empfehlung und wissenschaftliche Begründung der STIKO zur Grundimmunisierung von Personen im Alter von 12 – 17 Jahren mit dem COVID-19-Impfstoff Nuvaxovid von Novavax

Die STIKO erweitert die Empfehlung zur Grundimmunisierung mit dem adjuvantierten, proteinbasierten COVID-19-Impfstoff Nuvaxovid der Firma Novavax von ≥ 18-Jährigen um die Gruppe der Kinder und Jugendlichen im Alter von 12 – 17 Jahren. Das Impfschema sieht für die Grundimmunisierung zwei Impfstoffdosen vor, die im Abstand von mindestens 21 Tagen verabreicht werden.Peer Reviewe

Wissenschaftliche Begründung der STIKO zur Auffrischimpfung von Personen ab 18 Jahren mit dem COVID-19-Impfstoff Nuvaxovid (Novavax)

Die EMA hat der Europäischen Kommission An¬fang September 2022 die Ausweitung der bedingten Zulassung des monovalenten Impfstoffs Nuvaxovid der Firma Novavax zur Auffrischimpfung für Personen ab 18 Jahren empfohlen. Am 06.09.2022 erfolgte die Zulassung durch die Europäische Kommission. Daher empfiehlt nun die STIKO Personen ab 18 Jahren, bei denen produktspezifische medizinische Kontraindikationen gegen die zugelassenen COVID-19-mRNA-Impfstoffe bestehen, alternativ eine Auffrischimpfung mit Nuvaxovid. Die Auffrischimpfung mit Nuvaxovid ist auch möglich bei individuellem Wunsch nach entsprechender Beratung. Für 12 – 17-Jährige ist Nuvaxovid zur Auffrischimp¬fung derzeit nicht zugelassen, kann jedoch in dieser Altersgruppe ebenfalls bei produktspezifischen medizinischen Kontraindikationen für mRNA-Impfstoffe zur Auffrischimpfung eingesetzt werden (off-label-use). Eine Anwendung des Impfstoffs Nuvaxovid während der Schwangerschaft und Stillzeit wird weiterhin nicht empfohlen.Peer Reviewe

Escitalopram and Neuroendocrine Response in Healthy First-Degree Relatives to Depressed Patients – A Randomized Placebo-Controlled Trial

INTRODUCTION: The mechanisms by which selective serotonin re-uptake inhibitors (SSRI) act in depressed patients remain unknown. The serotonergic neurotransmitter system and the hypothalamic-pituitary-adrenal (HPA) system may interact. The aim of the AGENDA trial was to investigate whether long-term intervention with SSRI versus placebo affects the cortisol response in the dexamethasone corticotropin-releasing hormone (DEX-CRH) test in healthy first-degree relatives to patients with major depressive disorder (MDD). METHODS: Eighty healthy first-degree relatives to patients with MDD were randomized to escitalopram 10 mg versus matching placebo daily for four weeks. The primary outcome measure was the intervention difference in the change of the total area under the curve (CorAUC(total)) for plasma cortisol in the DEX-CRH test at entry to after four weeks of intervention. RESULTS: Change in CorAUC(total) showed no statistically significant difference between the escitalopram and the placebo group, p = 0.47. There were large intra- and inter-individual differences in the results of the DEX-CRH test. There was statistically significant negative correlation between the plasma escitalopram concentration and change in CorAUC(total), rho = -0.41, p = 0.01. Post-hoc analyses showed a statistically significant interaction between age and intervention group and change in log CorAUC(total). CONCLUSION: The present trial does not support an effect of escitalopram 10 mg daily compared with placebo on the HPA-axis in healthy first-degree relatives to patients with MDD. Increasing levels of escitalopram tended to decrease the HPA-response in the DEX-CRH test and this effect increased with age. TRIAL REGISTRATION: ClinicalTrials.gov NCT00386841

Wissenschaftliche Begründung der STIKO zur Grundimmunisierung von Personen ≥ 18 Jahre mit dem COVID-19-Impfstoff Nuvaxovid von Novavax

Nuvaxovid, ein adjuvantierter Proteinimpfstoff der Firma Novavax, ist seit dem 20.12.2021 in der EU für die Grundimmunisierung gegen COVID-19 zugelassen. Die Verfügbarkeit dieses Impfstoffs ist für Ende Februar 2022 angekündigt. Die STIKO empfiehlt die Grundimmunisierung mit Nuvaxovid für Personen ≥ 18 Jahre mit 2 Impfstoffdosen von je 5 μg des SARS-CoV-2-Spikeproteins im Abstand von mindestens 3 Wochen. Der Impfstoff ist bisher nicht für die Auffrischimpfung zugelassen.Peer Reviewe

Rationale and design of the participant, investigator, observer, and data-analyst-blinded randomized AGENDA trial on associations between gene-polymorphisms, endophenotypes for depression and antidepressive intervention: the effect of escitalopram versus placebo on the combined dexamethasone-corticotrophine releasing hormone test and other potential endophenotypes in healthy first-degree relatives of persons with depression

<p>Abstract</p> <p>Background</p> <p>Endophenotypes are heritable markers, which are more prevalent in patients and their healthy relatives than in the general population. Recent studies point at disturbed regulation of the hypothalamic-pituitary-adrenocortical axis as a possible endophenotype for depression. We hypothesize that potential endophenotypes for depression may be affected by selective serotonin re-uptake inhibitor antidepressants in healthy first-degree relatives of depressed patients. The primary outcome measure is the change in plasma cortisol in the dexamethasone-corticotrophin releasing hormone test from baseline to the end of intervention.</p> <p>Methods</p> <p>The AGENDA trial is designed as a participant, investigator, observer, and data-analyst-blinded randomized trial. Participants are 80 healthy first-degree relatives of patients with depression. Participants are randomized to escitalopram 10 mg per day versus placebo for four weeks. Randomization is stratified by gender and age. The primary outcome measure is the change in plasma cortisol in the dexamethasone-corticotrophin releasing hormone test at entry before intervention to after four weeks of intervention. With the inclusion of 80 participants, a 60% power is obtained to detect a clinically relevant difference in the primary outcome between the intervention and the placebo group. Secondary outcome measures are changes from baseline to four weeks in scores of: 1) cognition and 2) neuroticism. Tertiary outcomes measures are changes from baseline to four weeks in scores of: 1) depression and anxiety symptoms; 2) subjective evaluations of depressive symptoms, perceived stress, quality of life, aggression, sleep, and pain; and 3) salivary cortisol at eight different timepoints during an ordinary day. Assessments are undertaken by assessors blinded to the randomization group.</p> <p>Trial registration</p> <p>Local Ethics Committee: H-KF 307413</p> <p>Danish Medicines Agency: 2612-3162.</p> <p>EudraCT: 2006-001750-28.</p> <p>Danish Data Agency: 2006-41-6737.</p> <p>ClinicalTrials.gov: NCT 00386841</p